McGraw-Hill Specialty Board Review Pediatrics, 2nd Edition

Chapter 12. INFECTIOUS DISEASE

CASE 94: A 12-MONTH-OLD WITH DELAYED IMMUNIZATIONS

A 12-month-old boy is brought to your office for evaluation of a cough and runny nose. You note that this is the child’s first visit to your office. On questioning the child’s mother, she informs you that the infant has been seen by another physician 3 times since birth but now needs to change health-care providers since moving to a new city. After review of the child’s immunization record, you note that the child has received only one set of immunizations including diphtheria and tetanus toxoid, and acellular pertussis (DTaP) vaccine, inactive poliovirus vaccine (IPV), hepatitis B vaccine, and Haemophilus influenzae type b (Hib) conjugate vaccine at age 4 months. Two days later, he had fever recorded by the mother at 102.2°F (39°C). The mother is aware that her son is behind with immunizations, based on his age. She tells you that except for the 4-monthold visit, her son had cold symptoms like today’s symptoms, so immunizations were not administered.

On physical examination the child is alert and active. His height and weight are at the 10th percentile. The temperature is 100.4°F (38°C). Examination of the ears is normal. Clear rhinorrhea is present. Examination of both lungs and heart is normal. No hepatosplenomegaly is found.

SELECT THE ONE BEST ANSWER

1. The most likely reason the infant is behind for age with immunizations is

(A) the mistaken belief that a minor illness with fever contraindicates immunization

(B) failure to show up for vaccination visits

(C) the boy has an undefined immunodeficiency

(D) he had a fever of 102.2°F (39°C) after the first set of immunizations

(E) he has an unimmunized household contact

2. The infant receives DTaP-hepatitis B-IPV, Hib conjugate, pneumococcal conjugate vaccine, and measles, mumps, rubella (MMR) vaccines. The minimum interval before the next administration of a third dose of DTaP-IPV-hepatitis B vaccine should be

(A) 2 weeks

(B) 4 weeks

(C) 6 weeks

(D) 8 weeks

(E) 12 weeks

3. The infant’s mother asks you whether her infant should receive influenza vaccine. All of the following are recommended to receive influenza vaccine during the autumn of each year before the start of influenza season except

(A) a 5-year-old girl with asthma

(B) an 18-month-old healthy boy

(C) a 3-year-old girl with allergic rhinitis

(D) a 16-year-old healthy adolescent girl

(E) no exceptions; all of the above should receive influenza vaccine

4. The mother also asks you about meningococcal vaccine, which she remembers her older brother receiving before travel outside the country and wonders whether her infant should also receive that vaccine. You tell her that a conjugated meningococcal vaccine (MCV4) is licensed and indicated for all but one of the following

(A) a 21/2-year-old child traveling to sub-Saharan Africa

(B) a 5-year-old child whose spleen has just been removed after trauma

(C) a 19-year-old college student living in an apartment rather than on-campus housing

(D) a 3-year-old child with sickle cell disease

(E) an 8-month-old child with human immunodeficiency virus (HIV) infection

5. The mother tells you that she had never heard of the pneumococcal conjugate vaccine (PCV-13) that you also are recommending for her infant. Which of the following statements about Prevnar is true?

(A) PCV-13 can protect children against up to 23 different serotypes of Streptococcus pneumoniae

(B) a 12-month-old infant should only receive a single dose of the vaccine

(C) infants of very low birthweight (≤1500 g) should be immunized at a chronological age of 6-8 weeks

(D) the serotypes in the vaccine account for about two-thirds of the serotypes that cause invasive disease in children younger than 6 years in the United States

(E) the vaccine should not be administered to a 7-year-old healthy child or part of a catch-up regimen

6. Management of a preterm infant lighter than 2000 g at birth who is born to a mother who is hepatitis B surface antigen (HBsAg) positive includes all but

(A) hepatitis B vaccine within 12 hours of birth

(B) Hepatitis B immunoglobulin (HBIG) within 12 hours of birth

(C) immunization with 4 vaccine doses of hepatitis B vaccine including the dose given at birth

(D) check anti-HBs antibody and HBsAg at 9-15 months of age

(E) check anti-HBs antibody 1-2 months after the last dose

7. Hepatitis A vaccine is recommended for which of the following situations?

(A) an 11-month-old girl traveling with her family to India

(B) a 4-year-old girl from Oklahoma entering preschool

(C) a 12-year-old adolescent boy exposed to hepatitis A virus (HAV)-contaminated food 4 weeks ago

(D) a 24-year-old male pediatric resident working in a hospital setting

(E) a newborn infant of an HAV-infected mother

8. An 8-year-old girl sustains a large laceration contaminated with dirt after falling from her bike. Her mother can’t recall how many doses of tetanus toxoid her daughter has received. Management of tetanus prophylaxis in this situation of unknown history of prior doses of tetanus toxoid includes

(A) adult-type Td

(B) tetanus immune globulin (TIG)

(C) tetanus and diphtheria (Td) toxoid vaccine and TIG

(D) Hib conjugate vaccine containing tetanus toxoid and TIG

(E) Tdap (acellular pertussis vaccine)

9. A number of different licensed acellular pertussis vaccines contain one or more immunogens derived from Bordetella pertussis organisms. The antigen that is common to all of the US-licensed acellular pertussis vaccines includes

(A) pertussis toxin (PT)

(B) filamentous hemagglutinin (FHA)

(C) fimbrial proteins (agglutinogens)

(D) pertactin (outer membrane 69-kDa protein)

(E) lipopolysaccharide endotoxin (LPS)

10. Acellular pertussis vaccine contained in DTaP is appropriate to administer in the following circumstance

(A) a 5-year-old girl who has received DT vaccine at 2, 4, and 6 months of age and DTaP vaccine at 12, 18, and 24 months of age

(B) a 24-year-old adult working in a hospital experiencing a pertussis outbreak

(C) a 3-year-old unimmunized boy

(D) a 6-month-old infant girl with seizures poorly controlled with anticonvulsant therapy

(E) an 11-year-old adolescent girl with an unknown history of prior pertussis immunization

11. An outbreak of measles is occurring in a large urban city in the United States. Measles vaccine can be administered to children as young as

(A) 4 weeks

(B) 4 months

(C) 6 months

(D) 9 months

(E) 12 months

12. Which of the following is a contraindication to the administration of the (live virus) measles vaccine

(A) history of egg allergy

(B) history of allergy to chickens or feathers

(C) an 8-year-old girl with HIV with evidence of moderate immunosuppression with a CD4 percentage of 16

(D) a 12-month-old child with a family history of seizures

(E) immune globulin intravenous (IGIV) given 6 months ago for treatment of Kawasaki disease

13. A mother of a 2-year-old child receives MMR vaccine and subsequently finds out that she was pregnant when the vaccine was administered. The following statement about rubella vaccine and pregnancy is true

(A) receipt of rubella vaccination during pregnancy is an indication to terminate the pregnancy

(B) immune globulin (IG) should be administered to the pregnant woman

(C) immunizing the mother’s 2-year-old child places the mother at risk for rubella infection

(D) no cases of congenital rubella syndrome have been reported in women who have received rubella vaccine during pregnancy

(E) serologic testing for rubella should be done routinely before immunization in all postpubertal women

14. All of the following individuals do not require rubella immunization except

(A) a woman in the third trimester of pregnancy

(B) a woman born in 1953 with no history of previous rubella vaccine

(C) a 13-year-old adolescent girl with a previous clinical diagnosis of rubella

(D) a 6-year-old boy who received 2 doses of MMR vaccine at age 2 and 3 years

(E) a 2-year-old child receiving induction cancer chemotherapy

15. Exposure to all of the following animals is an indication of postexposure prophylaxis with rabies vaccine and rabies immune globulin (RIG) except

(A) raccoons

(B) woodchucks

(C) skunks

(D) squirrels

(E) bats

16. You are asked about the safety of IPV by the mother of a 12-month-old infant. You should tell her that

(A) oral polio vaccine (OPV) can cause vaccineassociated paralytic poliomyelitis (VAPP), and the risk is highest after the third dose of vaccine

(B) severe egg allergy (anaphylaxis) is a contraindication to poliovirus vaccine

(C) IPV is recommended for household contacts of patients with immunodeficiency disorders

(D) fever occurs in approximately 40% of infants who receive IPV vaccine

(E) OPV vaccine is preferred over IPV vaccine for routine immunization of infants in the United States

17. A 2-month-old infant receives a dose of Hib conjugate vaccine as a component of the pentavalent DTaP-IPV/Hib vaccine. Then at 4 months he receives a different Hib conjugate vaccine, PRP-T (tetanus toxoid conjugate). The next dose should be administered at age

(A) 6 months

(B) 9 months

(C) 12 months

(D) 15 months

(E) 18 months

18. Compared with natural infection with varicella, varicella vaccine is

(A) more likely to result in herpes zoster

(B) more likely to result in transmission of virus to contacts

(C) more likely to result in mild varicella disease if breakthrough varicella infection occurs

(D) more likely to result in the serious adverse event of encephalitis

(E) more likely to be associated with secondary bacterial infection

ANSWERS

1. (A) Minor illnesses (eg, upper respiratory infection or gastroenteritis, with or without fever) are not a contraindication to any of the routine childhood vaccines. A fever of 104.9°F (40.5°C) within 48 hours after previous immunization with a dose of diphtheria and tetanus toxoids and DTaP is considered a precaution, not a definite contraindication, to subsequent administration of DTaP vaccine. There are 4 true contraindications to immunizations: (1) previous anaphylactic reaction to an immunization, (2) encephalopathy within 7 days after a previous dose of DTP, DTaP, or Tdap, (3) severe immunocompromise (for live vaccines only), (4) pregnancy (live vaccines only). Mild illnesses or fever do not alter the safety profile or the immune response of a vaccine.

2. (B) The recommended interval to the second dose of vaccine is 2 months. However, for children 4 months to 6 years of age who start late or are more than 1 month behind, the minimum interval between doses 2 and 3 is 4 weeks for DTaP and IPV vaccines and 3 weeks for hepatitis B. The third dose of hepatitis B vaccine should be at least 16 weeks after the first dose.

3. (E) The Advisory Committee on Immunization Practices (ACIP) has now recommended routine influenza vaccine for all individuals older than 6 months of age. This is in part because hospitalization rates are highest for complicated influenza in the first 2 years of life (Table 94-1). Rates of hospitalization for these young subjects are comparable with adults older than 65 years of age. Decreasing influenza transmission among children has the potential to reduce spread among their household contacts and within the community. There are 2 types of influenza vaccine: LAIV (live attenuated) and TIV (trivalent inactivated); both vaccines contain egg protein. Children younger than 9 years of age receiving their first influenza vaccine require a second dose in 4 weeks. Contraindications for influenza immunization are allergy to any vaccine component, history of Guillain-Barré syndrome, and moderate or severe intercurrent illness.

TABLE 94-1 Estimated Rates of Influenza-Associated Hospitalizations/100,000 Persons

 

STUDY YEARS

AGE GROUP

HIGH RISK

HEALTHY

 

1973-1993

0-11 mo

1900

496-1038*

 

1-2 yr

800

186

 

3-4 yr

320

86

 

5-14 yr

92

41

 

*The low estimate is for infants 6-11 months, and the high estimate is for infants age 0-5 months.
Data from: Neuzil KM, Mellen BG, Wright PF, et al. Effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000;342:225.

4. (E) The 8-month-old child with HIV infection is too young to receive meningococcal vaccine. There are two meningococcal conjugate vaccines (MCV4) licensed for use in children. One manufactured by Sanofi Pasteur is approved for use in children 9 months of age and older. The other vaccine, manufactured by Novartis Vaccines and Diagnostics, is licensed for use in children as young as 2 years of age, although there is no current recommendation for the routine use of either vaccine in young children. The MCV4 vaccines are preferred over the unconjugated, older tetravalent polysaccharide vaccine, MPSV4. Health care providers should administer MCV4 to children ages 2-10 years (or 9 months to 10 years for the Sanofi vaccine) with persistent complement component deficiency, anatomic or functional asplenia, and other high-risk groups, including HIV. Any child previously immunized with MCV4 (at 9 months-6 years with the Sanofi version or at 2-6 years with the Novartis version) who remain at increased risk for disease will need to be re-immunized in 3 years. If the first dose of MCV4 is given after 7 years of age, the child will require a booster in 5 years. MCV4 is also recommended for routine immunization of all children 11-18 years of age and college freshmen living in dormitories.

5. (C) The newly licensed pneumococcal conjugate vaccine contains 13 serotypes that account for approximately 85% of the serotypes causing invasive pneumococcal infections (including bacteremia and meningitis) in children younger than 6 years of age in the United States. The 12-month-old infant should receive 2 doses of vaccine 6-8 weeks apart. The 7-year-old healthy child is too old for routine PCV-13 administration.

6. (D) Management of preterm infants lighter than 2000 g at birth if the mother is HBsAg positive should include HBIG within 12 hours after birth along with 4 doses of hepatitis B vaccine at 0, 1, 2-3, and 6-7 months of chronological age. The first dose of hepatitis B vaccine should be administered within 12 hours after birth. Recent recommendations are that the HBV series in infants born to HBsAg-positive mothers should be verified by serology (anti-HBs antibody). Some studies have demonstrated that a decreased seroconversion rate might occur among preterm infants lighter than 2000 g. By 1 month of chronological age, all preterm infants, regardless of weight, should respond serologically. If infants lighter than 2000 g at birth receive hepatitis B 1 at birth, this first dose should not be counted toward the completion of the 3-dose series; serologic conversion should be documented 1-2 months after series completion.

7. (B) In all states, including Oklahoma, routine immunization of children 1 year of age or older is now recommended. Postexposure prophylaxis with hepatitis A vaccine can be successful if the hepatitis A immunization is administered within 2 weeks of the exposure to hepatitis A–contaminated water or food. Routine hepatitis A immunization is not recommended for hospital personnel. Other high-risk groups for hepatitis A vaccine administration include men who have sex with men (MSM), intravenous drug abusers, people with chronic liver disease, family contacts of internationally adopted children, and “anyone for whom immunity is desired.”

8. (C) Tetanus immune globulin (TIG) should be administered if there is a history of less than 3 doses of tetanus toxoid administered or an unknown history, and there is not a clean minor wound. Clean minor wounds do not routinely require TIG. Other wounds such as those contaminated with dirt, puncture wounds, avulsions, penetrating wounds, burns, crush wounds, and frostbite require TIG. A dose of Td is indicated because when the status is unknown, it is reasonable to believe the child is one or more doses behind. There is no excess toxicity associated with an extra dose.

9. (A) There are 3 licensed acellular-pertussiscontaining vaccines available for use in the United States for children younger than age 7 in 7 different preparations or combination vaccines. There are also 2 acellular pertussis vaccines (Tdap) licensed and recommended for use in adolescents 11-12 years of age. There is no serologic correlate for the efficacy of pertussis vaccine. All of the licensed acellular pertussis vaccines contain pertussis toxoid, also termed lymphocytosis promoting factor (LPF).

10. (C) When administering DTaP vaccine to children who have previously received DT vaccine, the total number of doses of diphtheria and tetanus toxoids should not exceed 6 before the child reaches 7 years of age. Adolescents and adults should get Tdap vaccine with lower T and D content. Children with evolving neurologic disorders generally have pertussis vaccination deferred.

11. (C) For outbreak control of measles, monovalent vaccine can be administered to infants as young as 6 months of age. Because it is not available in the United States, MMR is usually substituted. Because of the substantial decrease in immunogenicity of measles vaccine given at 6 months of age, these infants should be reimmunized with MMR vaccine on schedule at 12-15 months of age and again at age 4-6 years.

12. (E) The usual dose of IGIV for treatment of Kawasaki disease is 2 g/kg. The administration of MMR vaccine should be deferred for 11 months after the administration of IGIV unless epidemic measles is occurring. Children with a history of egg allergy are at a low risk of anaphylactic reactions to MMR vaccine. Skin testing of children for egg allergy is not predictive of reactions to MMR vaccine. Most anaphylactic reactions are related to other vaccine components. Children with a history of anaphylactic reactions to gelatin or neomycin should only be vaccinated with MMR in settings where anaphylactic reactions can be properly managed. Children with HIV infection should receive MMR vaccine unless there is evidence of severe immunocompromise (CD4 percentage <15).

13. (D) Rubella vaccine is contraindicated during pregnancy. However, no cases of congenital rubella syndrome have occurred when susceptible women received rubella vaccine within 3 months of conception and delivered infants at term. There also has been no evidence of transmission of vaccine virus from immunized children to household contacts.

14. (C) The clinical diagnosis of rubella is not reliable to determine if one is susceptible to rubella. Rubella immunity should be documented by serologic testing during pregnancy. For children who received a first dose of rubella vaccine, a second dose is not necessary but is given because of the recommendations for 2-dose routine measles immunization. The second dose of MMR vaccine can be given as early as 4 weeks after the first dose as long as the first dose is administered at or after the age of 12 months.

15. (D) The bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, rabbits, and hares almost never require rabies postexposure prophylaxis. An exception for a rodent bite that does require prophylaxis is the bite of a woodchuck. All other animals listed in the answers require postexposure prophylaxis.

16. (C) The risk of VAPP is highest after the first dose of oral poliovirus vaccine, occurring in 1 in 700,000 recipients. OPV vaccine is contraindicated for household contacts of people with an immunodeficiency disorder because of the risk of spread of OPV to the affected person. OPV is no longer in use in the United States.

17. (A) The Hib component in the pentavalent vaccine is PRP-T. Therefore, the primary series for Hib can be completed by the third dose of Hib vaccine in either formulation at 6 months of age. A fourth dose of a Hib containing vaccine will be required at 12 months of age. PRP-OMP, the Hib vaccine contained in the combination PRP-OMP/hepatitis B vaccine has been unavailable in the United States although it remains licensed. For this Hib vaccine, the 6 month dose is not necessary.

18. (C) Varicella occurring in vaccine recipients is milder than in unimmunized children, with fewer vesicles, lower rates of fever, and more rapid recovery. Transmission of vaccines virus from one person to another is extremely rare.


SUGGESTED READING

Centers for Disease Control and Prevention. In: Atkinson W, Wolfe S, Hambursky J, McIntyre L, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 11th ed. Washington, DC: Public Health Foundation; 2009.

Pickering LK, Baker CJ, Kimberlin DW, Long SS. Red Book 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

Pickering LK, Orenstein WA. Active immunization. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone: 2008:48.

CASE 95: A 4-YEAR-OLD IMMUNOCOMPROMISED GIRL WITH AN EXPOSURE TO VARICELLA

A 4-year-old girl, whom you have followed in your practice since birth, was recently diagnosed with acute lymphoblastic leukemia (ALL). You had considered the diagnosis after she developed persistent fever, fatigue, back pain, and pallor. She had completed induction chemotherapy and is now in remission. The child’s mother calls your office to inform you she had received a phone call from her daughter’s preschool teacher. Two days ago another child developed a rash and was sent home. That child’s mother called today to inform the teacher that the child was seen by their pediatrician and diagnosed with chickenpox. The teacher then called your patient’s mother to inform her of this.

The preschool class that your patient attends meets Monday through Friday for 4 hours per day. Your patient was present in the class for the 4-hour period on the day that the other child developed the rash. Both children were also present in class on the previous day.

SELECT THE ONE BEST ANSWER TO THE FOLLOWING QUESTIONS

1. The first step in the management of varicella exposure in a child with leukemia is

(A) obtain a history of whether or not the child has had varicella

(B) administer the varicella vaccine to the child

(C) contact the pediatrician of the preschool classmate to verify the diagnosis of varicella

(D) draw blood for serologic testing on the child with leukemia

(E) determine whether the child is still receiving cancer chemotherapy

2. The child with leukemia has no history of varicella. It is next important to determine if

(A) the child has developed any other skin lesions

(B) the child has had serologic test results to determine his immune status regarding varicella

(C) the child has laboratory evidence of immunity for varicella

(D) the child has received IGIV in the past 3 weeks

(E) the child and her classmate played together in the same classroom with face-to-face contact

3. An immunocompromised child who is susceptible to varicella and at high risk for developing severe varicella should receive Varicella-Zoster Immune Globulin (VariZIG) or IGIV within what time period after exposure?

(A) 48 hours

(B) 72 hours

(C) 96 hours

(D) 120 hours

(E) 144 hours

4. All of the following types of exposure to zoster (shingles) are an indication for VariZIG or IGIV administration to susceptible people at higher risk for developing severe varicella except

(A) residing in one household

(B) face-to-face indoor play

(C) intimate contact (touching or hugging) with a person who has zoster

(D) newborn infant: onset of zoster in the mother 5 days or less before delivery or within 48 hours after delivery

(E) hospitalization in the same 2- to 4-bed room with another child who develops varicella

5. Candidates for VariZIG or IGIV provided an important exposure to varicella has occurred include

(A) a term newborn infant whose mother developed varicella 7 days before delivery of the infant

(B) a 21-year-old pregnant woman who has a history of varicella at age 5 years

(C) a hospitalized premature infant (<28 weeks’ gestation), regardless of maternal history of varicella or serologic varicella virus serostatus

(D) an 8-year-old girl with asymptomatic HIV infection with a history of varicella at age 2 years

(E) hospitalized premature infant (>28 weeks’ gestation) whose mother has a reliable history of varicella

6. A healthy term infant is born to a mother who develops varicella 7 days after delivery. Which of the following is true regarding management of this exposure?

(A) the absolute CD4 count and percentage of CD4 cells are high enough to prevent infection

(B) natural killer cell cytotoxicity prevents neonatal infection

(C) the infant is not believed to be high at risk of complicated viremia when varicella zoster is acquired by the respiratory tract

(D) acyclovir should be administered to prevent clinical varicella from occurring in the newborn

(E) varicella vaccine or IGIV is recommended for the young infant

7. VariZIG or IGIV is indicated in all of the following situations in which clinically important exposure to varicella occurs except

(A) a premature female infant of 25 weeks’ gestation whose mother had a history of varicella during childhood

(B) a 12-month-old girl with acquired immunodeficiency virus (AIDS) and significant immunodeficiency

(C) a 15-year-old boy with asthma who completed 10 days of a tapering course of steroids

(D) a 10-month-old male infant receiving immunosuppressive therapy after renal transplant

(E) a pregnant woman susceptible to varicella

8. The incidence of minor adverse events associated with the administration of IGIV such as fever, headache, myalgias, chills, and vomiting is primarily related to

(A) the concentration of administered IGIV

(B) the rate of infusion of IGIV

(C) the lot of IGIV administered

(D) the age of the patient receiving IGIV

(E) the number of doses of IGIV administered

9. An example of an infrequent serious reaction of IGIV therapy includes

(A) aplastic anemia

(B) acute renal failure

(C) HIV transmission

(D) Guillain-Barré syndrome

(E) acute hepatitis

10. IGIV is recommended for use in all of the following disorders except

(A) a 2-year-old boy with Kawasaki disease

(B) a 3-year-old girl with severe combined immunodeficiency disorder

(C) a 10-year-old boy with common variable immunodeficiency and hypogammaglobulinemia

(D) postexposure varicella prophylaxis where VariZIG is not available

(E) an 800 g premature infant

11. IGIV is recommended for an HIV-infected child in the following circumstance

(A) one episode of bacteremic pneumococcal pneumonia in the previous 12 months

(B) serum IgG level of 725 mg/dL or less (7.25 g/L)

(C) chronic parvovirus B19 infection

(D) chronic diarrhea caused by cryptosporidium

(E) cryptococcal meningitis

12. The risk of anaphylaxis is highest with IGIV administration in children with which type of deficiency?

(A) IgA

(B) IgD

(C) IgE

(D) properdin

(E) adenosine deaminase (ADA)

13. A 10-month-old healthy male infant traveling with his family to Africa was exposed 4 days ago to his 4-year-old native African cousin who was ill at the time with fever, cough, coryza, and conjunctivitis. The 4-year-old cousin was diagnosed with measles as have a number of children in the city where the family is visiting. The mother of the 10-month-old child makes an overseas phone call to your office asking your advice. Appropriate management of the 10-month-old includes

(A) MMR vaccine administration

(B) measurement of serum measles IgG antibody

(C) immune globulin 0.25 mL/kg by the intramuscular (IM) route

(D) immune globulin 0.25 mL/kg by the IV route

(E) monovalent measles vaccine administration

14. IG can be given to prevent or modify measles in a susceptible person within how many days of exposure?

(A) 1

(B) 4

(C) 6

(D) 10

(E) 14

15. A 9-month-old child attending day care comes to your office. The child is healthy, but his mother is concerned because another child of 21/years who attends the same day-care center was diagnosed with hepatitis A infection about 1 week ago. Appropriate management of the 9-month-old child includes

(A) administer hepatitis A vaccine to the child

(B) administer IG at dose of 0.02 mL/kg IM plus hepatitis A vaccine IM at a different site

(C) measure hepatitis A virus IgM to check for evidence of asymptomatic current infection

(D) measure hepatitis A virus IgG to check for evidence of past infection and immunity

(E) administer IG at dose of 0.02 mL/kg IM

16. IG for IM administration should be given within what time period after exposure to have more than 85% efficacy in preventing symptomatic hepatitis A infection?

(A) 3 days

(B) 7 days

(C) 14 days

(D) 21 days

(E) 28 days

17. A major limitation of IG for replacement therapy in antibody deficiency disorders is the need for deep IM injections. An alternative is slow subcutaneous administration of IG. Characteristics of this method of administration include all of following except

(A) less expensive than IGIV

(B) suitable for home therapy

(C) systemic allergic reactions occurring in 15% of recipients

(D) ability to deliver relatively large volumes of IG

(E) similar efficacy for prevention of serious infection primary immunodeficiency diseases compared with IGIV

18. A 13-year-old adolescent female with no prior history of hepatitis B immunization accidentally sticks herself with an insulin syringe that belongs to her uncle who has diabetes but also is known to be an HBsAg-positive person. Appropriate management of the adolescent would include

(A) initiate hepatitis B vaccine series

(B) initiate hepatitis B vaccine series and HBIG 0.06 mL/kg

(C) administer HBIG 0.06 mL/kg

(D) administer IGIV 400 mg/kg and initiate hepatitis B vaccine series

(E) test for HBsAg and anti-HBs antibody

ANSWERS

1. (A) Immunocompromised children are candidates for varicella zoster immune globulin (VariZIG) or IGIV if there is no prior history of varicella.

2. (E) Past evidence of immunity is not helpful at this point. Immunocompromised patients with no history of varicella and low levels of antibody detected by sensitive antibody assays have developed varicella. Face-to-face contact indoors with a playmate for greater than 1 hour is considered an exposure that should warrant administration of VariZIG or IGIV.

3. (C) Susceptible individuals at high risk for developing severe varicella should receive VariZIG or IGIV within 96 hours of exposure.

4. (D) VariZIG or IGIV is not indicated if the mother has zoster. In this case the mother has had varicella in the past so the infant should have transplacentally acquired varicella zoster antibody. VariZIG or IGIV would be indicated for a newborn if the mother had developed varicella.

5. (C) VariZIG or IGIV would be indicated for the premature infant beyond a 28-week gestation if the mother lacks a reliable history of varicella or serologic evidence of protection. Premature infants (<28 weeks’ gestation or ≤1000 g birthweight) should receive VariZIG or IGIV regardless of maternal history of varicella. The term newborn infant whose mother developed varicella 5 or more days before delivery should have received transplacental antibody from the mother.

6. (C) Newborn infants whose mother had onset of varicella within 5 days before delivery or within 48 hours after delivery should receive VariZIG or IGIV. If the onset of the mother’s rash is within 5 days of delivery, the infant has been exposed to maternal viremia in the absence of transplacental varicella antibody. If onset of the mother’s rash is within 48 hours after delivery, the infant may be exposed to maternal viremia without the possible protective effect of transplacental antibody. If mother has onset of rash 3 or more days after delivery, the route of infection will be the respiratory route and not via the bloodstream. VariZIG, IGIV, or acyclovir are all not recommended for this exposure by the American Academy of Pediatrics.

7. (C) A 10-day course of tapering steroids would not be considered an immunosuppressive dose, and therefore VariZIG or IGIV is not indicated. Children who receive high doses of corticosteroids (≥2 mg/kg per day of prednisone or its equivalent) given daily or on alternate days for 14 days or more should not receive live-virus vaccines until corticosteroids have been stopped for at least 1 month.

8. (B) The cause of these minor reactions may be related to the formation of IgG aggregates during manufacture or storage. Most reactions will subside when the rate of infusion is decreased.

9. (B) Patients 65 years or older, patients receiving concomitant nephrotoxic agents, patients with diabetes mellitus, preexisting renal disease, hypovolemia, and sepsis are at increased risk for acute renal failure and renal insufficiency. Most reports of adverse renal events have involved IGIV preparations containing sucrose.

10. (E) IGIV is not recommended for routine use in preterm infants with birthweights 1500 g or less to prevent late-onset infection.

11. (C) Other indications for IGIV therapy in HIVinfected children include hypogammaglobulinemia (IgG level <400 mg/dL), 2 or more serious bacterial infections (bacteremia, pneumonia, meningitis) in a 1-year period, and failure to form antibodies to common antigens after immunization.

12. (A) Anaphylactic reactions are induced by anti-IgA and can occur in children with absence of circulating IgA but have IgG antibodies to IgA. In these situations with IgA deficiency and hypersensitivity reactions, IGIV with extremely low IgA content is available. Screening for IgA deficiency is not routinely recommended.

13. (C) Immune globulin can be given to prevent or modify measles in susceptible individuals, particularly children younger than 1 year of age, pregnant women, and immunocompromised children who are household contacts of a person with measles. The dose of 0.5 mL/kg is used for immunocompromised children (Table 95-1). Monovalent measles vaccine is seldom available.

14. (C) IG can be given to prevent or modify measles in a susceptible person within 6 days of exposure.

15. (E) The appropriate management is administration of IG alone. The child is too young for hepatitis A vaccine. Although most infected children in childcare settings are asymptomatic or have nonspecific symptoms, serologic testing is not recommended. Testing adds unnecessary cost and may delay administration of IG.

TABLE 95-1 Indications for the Use of Immune Globulin

 

INDICATION

COMMENT

 

Replacement therapy in antibody deficiency disorders

Usual dose 100 mg/kg per month by IM route often now given by IV route

Slow subcutaneous administration is safe.

Hepatitis A prophylaxis

International travel by children younger than 1 yr (<3 mo stay, 0.02 mL/kg IM; 3 to 5 mo stay, 0.06 mL/kg IM; long-term stay, 0.06 mL/kg IM every 5 mo)

Postexposure, if <2 weeks since exposure: IG, 0.02 mL/kg IM if <12 mo, HAV vaccine if 12 mo-40 yr

Measles prophylaxis

Postexposure, 0.25 mL/kg IM within 6 days of exposure, 0.50 mL/kg IM if immunocompromised

Target groups: children <1 yr, older children not vaccinated, immunocompromised children, pregnant women

 

Abbreviations: HAV, hepatitis A virus; IGIV, immune globulin intravenous.

16. (C) For immunoprophylaxis after exposure to hepatitis A for children younger than 12 months of age, IG should be administered within 2 weeks after exposure to HAV (Table 95-1).

17. (C) If IG is administered by the subcutaneous route, systemic allergic reactions occur in less than 1% of infusions and local tissue reactions are generally mild.

18. (B) In this clinical situation, the prophylaxis is driven primarily by the exposed adolescent not being immunized with hepatitis B vaccine and the source known to be HBsAg positive. If the adolescent was unimmunized and source is unknown or not tested, the recommendation is to initiate the hepatitis B vaccine series alone.


SUGGESTED READING

Goldman DC: Passive immunization. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008:41.

Pickering LK, Baker CJ, Kimberlin DW, Long SS. Red Book2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

CASE 96: A 2-YEAR-OLD AT DAY CARE WITH FEVER, ANOREXIA, AND NAUSEA

A 2-year-old boy is brought to your office with a 4-day history of fever followed by decreased appetite. His mother denies vomiting or diarrhea, but she thinks that he may be nauseated after eating or drinking. She also indicates that his stool pattern has changed. For the past 3 days he has only had 2 stools. The last stool was firm in consistency. The child has attended day care for the past 8 weeks. His immunizations, including PCV-13, a pneumococcal conjugate vaccine, have been documented to be up to date for age with the exception of hepatitis A and B.

On physical examination the child appears to be ill. The temperature is 101.8°F (38.8°C). The child’s weight is 0.1 kg less than when seen approximately 2 months ago for a physical examination before entering day care. There is no rash. The examination of the lungs and heart is normal. There is epigastric fullness and mild right upper quadrant pain upon examination of the abdomen.

SELECT THE ONE BEST ANSWER

1. The diagnostic test most likely to be helpful in establishing the diagnosis in this child is

(A) serologic test for hepatitis A IgM antibody

(B) stool culture for SalmonellaShigellaCampylobacter

(C) enzyme immunoassay of stool for Giardia antigen

(D) serologic test for hepatitis E IgM antibody

(E) stool examination for ova and parasites

2. Hepatitis A infection is identified in an employee of the day-care center. This is the second outbreak of hepatitis A in the center in the past year. The appropriate management of a 3-year-old child who also attends the day care is

(A) immune globulin 0.02 mL/kg IM

(B) immune globulin 0.06 mL/kg IM

(C) immune globulin 0.02 mL/kg IM and hepatitis A vaccine

(D) hepatitis A vaccine

(E) measure HAV-specific total and IgM antibody

3. How long should the employee be excluded from the day-care center in relation to the onset of the illness?

(A) 1 week

(B) 2 weeks

(C) 3 weeks

(D) 4 weeks

(E) 6 weeks

4. A 3-year-old child sustains a puncture to the right hand after a bite from Flopsy, her pet cat. Within 24 hours the hand is swollen, erythematous, and tender. There is scant serous discharge at the site of the wound. The most likely etiology is

(A) Staphylococcus aureus (B) Francisella tularensis (C) Bartonella henselae (D) chikungunya virus

(E) Pasteurella multocida

5. A 9-year-old girl who has gone hiking in the woods with her father is found to have a tick attached to her neck. A number of tick-borne diseases can occur after a tick bite. These would include all of the following except

(A) Lyme disease

(B) tularemia

(C) ehrlichiosis

(D) leptospirosis

(E) Rocky Mountain spotted fever

6. In a child-care setting, the use of prophylactic antibiotics would be most appropriate for child-care contacts of

(A) a child who has streptococcal toxic shock syndrome

(B) an infant who has pertussis

(C) an infant who has influenza A

(D) a child who has invasive Streptococcus pneumoniae disease

(E) a child who has shigella infection

7. An outbreak of diarrhea has occurred in a day-care center. Important infection control measures in the setting include all but

(A) written procedures for handwashing

(B) diaper-changing areas should not be located near food preparation areas

(C) exclusion of children with diarrhea or stools that contain blood or mucus

(D) removal of all toys from rooms where children eat and play

(E) diaper-changing procedures should be posted at the changing area

8. The mother of a 3-year-old girl with HIV infection is considering enrolling her child in a nearby daycare center. You inform her that

(A) the child should not be placed in the day-care center because of the potential risk of transmission to others

(B) the child care providers at the day-care center will need to be informed of the child’s HIV status

(C) the child should not attend the day-care center because of the risk of exposure to varicella

(D) the day-care providers should use standard precautions for handling spills of blood and blood-containing body fluids

(E) routine screening of children in day care for HIV is recommended

9. The mother of a 14-year-old adolescent boy calls you to inform you a 16-year-old girl at her son’s high school died of meningitis. The mother’s son is a close friend of the girl’s boyfriend. You had just heard the same day from one of your colleagues about an adolescent girl who died of meningococcal meningitis. You tell the mother that her son should

(A) have a throat specimen sent for Neisseria meningitidis culture

(B) receive a single dose of ceftriaxone

(C) receive a single dose of ciprofloxacin

(D) be excluded from school for the next 7 days

(E) be observed closely for a febrile illness

10. An 18-month-old boy who attends day care has diarrhea, fever, vomiting, and hematochezia. A stool culture sent grows Salmonella, serotype Newport. Methods recommended to limit the spread of this organism include

(A) stool cultures for all attendees and staff members

(B) frequent handwashing measures with staff training

(C) exclusion of asymptomatic children shedding Salmonella in the stool

(D) antibiotic therapy for all exposed children in the day care with diarrhea

(E) antibiotic therapy for the child with proven Salmonella infection

11. A 3-year-old girl who attends child care develops fever, abdominal cramps, and mucoid stools with blood. A stool culture grows Shigella sonnei. Correct management would include

(A) stool cultures on all child-care attendees of the child-care facility

(B) administration of an antidiarrheal compound to shorten the duration of diarrhea

(C) treatment of children with mild symptoms with an antibiotic to prevent spread

(D) exclusion of the 3-year-old child from child care for 5 days after the onset of diarrhea

(E) stool cultures on all staff members of the child-care facility

12. There are 3 neonates in a newborn intensive care unit (NICU) who are diagnosed with respiratory syncytial virus (RSV) infection in a span of 2 days. All of the following are important methods of preventing the further spread of RSV except

(A) cohorting infected infants

(B) excluding staff with respiratory illness from the NICU

(C) respiratory isolation of all infants positive for RSV

(D) laboratory screening of all infants in the NICU for RSV

(E) contact isolation of all infants positive for RSV

13. A 13-year-old boy has a 2-week history of fever, cough productive of sputum, night sweats, and fatigue. A chest radiograph performed shows a right lower lobe infiltrate, and a Mantoux test is placed. The test shows a 16 mm zone of induration. Methods to prevent spread of tuberculosis in this patient in the hospital setting include

(A) droplet precautions

(B) using a mask within 3 feet of the patient

(C) providing the patient with a private room using negative air-pressure ventilation

(D) wearing a gown and gloves at each patient encounter

(E) using hand hygiene before using gloves and after glove removal

14. A mother of one of your 13-year-old adolescent female patients calls you because she suspects one of her daughter’s classmates may have HIV infection. You counsel her that

(A) HIV is acquired through contact with tears

(B) HIV in a school-age child must be reported to school personnel

(C) the HIV status of a school-age child may only be known by the child’s parents, other guardians, and the physician

(D) HIV infection in adolescents is primarily acquired perinatally from mothers with HIV infection

(E) HIV in adolescents is acquired primarily by blood transfusion

15. A 12-year-old boy from China with normal growth and development is known to have hepatitis B infection: hepatitis B surface antigen positive, antibody to hepatitis B core antigen positive, and antibody to hepatitis B surface antigen negative. A mother of one of your patients who is in the same classroom is concerned because her son has only received one dose of hepatitis B vaccine 1 year ago. You recommend that her child

(A) begin the 3-dose series of hepatitis B vaccine again immediately

(B) complete the 3-dose series of hepatitis B vaccine with 2 more doses

(C) receive hepatitis B immune globulin and hepatitis B vaccine

(D) have blood drawn for hepatitis B serology and be given hepatitis B vaccine, if seronegative

(E) be transferred to a different classroom in the same school

16. A pediatric resident sustains a needlestick injury while starting a peripheral intravenous line on a 3-year-old child. The resident is concerned about possible HIV infection. You counsel the resident that

(A) postexposure prophylaxis with antiretroviral agents is recommended if the exposure occurred within 96 hours

(B) solid needles carry the highest risk of transmission of HIV

(C) antiretroviral agents should be strongly considered with a needlestick injury from an unknown occupational source

(D) HIV and HBV are the only viruses that can be transmitted by needlestick injury

(E) the transmission risk from a single percutaneous needlestick involving HIV-contaminated blood is approximately 0.3%

17. A 15-year-old adolescent girl is diagnosed with meningococcemia. She has a 4-year-old brother and an 11-month-old sister at home. Appropriate management of her siblings includes

(A) nasopharyngeal cultures for N meningitidis (B) meningococcal quadrivalent vaccine

(C) single dose of azithromycin to both children

(D) rifampin given every 12 hours for 2 days

(E) close observation for a febrile illness

18. A 2-year-old child living in a residential institution for developmentally disabled children should receive all of the following vaccinations for prevention of infection except

(A) pneumococcal conjugate vaccine

(B) hepatitis A vaccine

(C) hepatitis B vaccine

(D) meningococcal conjugate vaccine

(E) varicella vaccine

ANSWERS

1. (A) This child most likely has acute hepatitis A infection. Salmonella, shigella, and campylobacter most often have associated diarrhea. Giardia can present in a similar way to hepatitis A, but the patient seldom appears ill or has a fever. Diagnosis is confirmed by measuring immunoglobulin (Ig) M antibodies to hepatitis A. This antibody usually disappears within 4 months but can persist longer. The serum IgM anti-HAV antibody is usually present at the onset of clinical illness.

2. (D) Immune globulin (IG) is indicated if the exposure has been within the previous 2 weeks for children younger than 12 months. In this clinical situation, hepatitis A vaccine alone should be administered to the child. Hepatitis A vaccine has been shown to be as effective as IG for postexposure prophylaxis in the age groups 12 months to 40 years.

3. (A) Children and adults with acute hepatitis A infection who attend or work in child-care settings should be excluded for 1 week after onset of illness.

4. (E) This child has a wound infection occurring within 24 hours of a bite. The description is typical of an infection caused by Pasteurella multocida. Transmission occurs most commonly from the bite or scratch of a cat or dog. Infection can also occur after bite injuries from lions, tigers, rats, and rabbits. Francisella, Bartonella, and chikungunya virus do not cause acute cellulitis like this. S aureus is possible but much less common.

5. (D) Leptospirosis is caused by spirochetes of the genus Leptospira (see Figure 96-1). Humans become infected through contact of mucosal surfaces or abraded skin with contaminated soil, water, or animal tissues. In the United States, dogs and farm animals are important reservoirs in addition to rats.

art

FIGURE 96-1. Scanning electron micrograph of leptospires. (Reproduced, with permission, from Fauci AS, Kasper DL, Braunwald E, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill; 2008: Fig. 164-1.)


6. (B) Chemoprophylaxis is indicated for childcare contacts of a child with pertussis infection. Chemoprophylaxis in child-care settings is also recommended for meningococcal disease. Chemoprophylaxis is also recommended when 2 or more cases of invasive H influenzae type b disease have occurred within 60 days, although such an event is exceedingly rare in the vaccine era. No chemoprophylaxis, however, is recommended for people exposed to a patient with serotype f disease.

7. (D) All frequently touched toys in rooms where infants and toddlers stay should be cleaned and disinfected daily, but it is not necessary to remove them. For older children who are toilet trained, toys should be cleaned weekly and when soiled.

8. (D) Children with HIV infection do not need to be excluded from child care. Standard precautions should be adopted by the child-care center for handling spills of blood and blood-contaminated body fluids and wound drainage of all children. Transmission of HIV has not occurred through day-to-day contact in child-care centers. Child-care providers do not need to be informed of the HIV status of any child attending child care.

9. (E) In this scenario, there is only indirect contact; that is, the only contact is with a high-risk contact but no direct contact with the index patient. This is a low-risk situation, and chemoprophylaxis is not recommended (Table 96-1).

10. (B) Children with Salmonella gastroenteritis may return to day care once they are asymptomatic. Approximately 50% of children younger than 5 years continue to excrete Salmonella for 12 weeks after infection. Antimicrobial therapy is not indicated for uncomplicated Salmonella gastroenteritis because therapy does not shorten the disease course and may prolong duration of carriage.

11. (C) All symptomatic individuals in a child-care facility with Shigella infection should receive antimicrobial therapy. In mild disease, the primary indication for treatment is to prevent spread of Shigella throughout the day-care center. Child-care attendees or staff members with symptomatic infection should be excluded until the diarrhea has resolved.

12. (E) The correct transmission-based precautions in the hospital setting to prevent transmission of RSV infection is contact precautions.

TABLE 96-1 Chemoprophylaxis For Contacts of Individuals With Invasive Meningococcal Disease

 

HIGH RISK (RECOMMENDED)

LOW RISK (NOT RECOMMENDED)

REGIMENS

 

Household contact

Casual contact (no exposure to oral secretions)

Rifampin (2 days, bid both days)

Childcare contact ≤7 days before illness

Indirect contact (only contact is high-risk contact)

Ceftriaxone (single dose)

Direct exposure to index patient’s secretions (kissing, sharing toothbrush or utensils)

Health-care professional with no direct exposure to patient’s oral secretions

Ciprofloxacin (single dose)

Mouth-to-mouth resuscitation, intubation, suctioning

   

Frequently slept/ate in same dwelling during 7 days before onset of illness

   

13. (C) In the hospital setting, the correct transmissionbased precautions to prevent spread of Mycobacterium tuberculosis is airborne precautions. Children younger than 12 years of age with pulmonary tuberculosis are rarely contagious because cavitary disease is rare and cough is not productive so there is little or no expulsion of bacilli, although precautions are generally instituted nevertheless. If a patient is receiving adequate antituberculosis therapy with cough resolved and 3 sputum smears (if available) are negative for acid-fast bacilli, the person can be considered noncontagious.

14. (C) Child-care or school providers need not be informed of the HIV status of a child who is attending a child-care center or school. In the absence of blood exposure, HIV is not acquired through the types of contact that occur in school settings, including contact with saliva or tears. HIV transmission among adolescents is attributed primarily to two categories of sexual contact: heterosexual or between MSM.

15. (B) There is no increased risk of transmission of hepatitis B infection in the school setting. An exception is that residents and staff of institutions for people with developmental disabilities represent a high-risk group for hepatitis B virus infection and should be immunized. In the clinical situation in the question, the classmate of the 12-year-old who is the hepatitis B surface antigen positive should complete the 3-dose series. It is not necessary to begin the series again even though the last dose of vaccine was 1 year previously.

16. (E) The risk of transmission from a percutaneous needle accident is highest with hollow-bore needles. Antiretroviral therapy is generally not recommended if the source of a needlestick injury is not known in the nonoccupational setting, such as injuries from discarded needles. Finally, needlestick injuries can also result in hepatitis C virus transmission.

17. (D) Household contacts are in the high-risk category for contacts of individuals with meningococcal disease. Rifampin, ceftriaxone, or ciprofloxacin can be used for chemoprophylaxis (Table 96-1).

18. (D) Children living in residential institutions should receive all the routine childhood vaccines. In this setting children as well as staff are at increased risk of acquiring hepatitis B virus infection. Outbreaks of hepatitis A virus infection can occur in residential institutions. The routine vaccination of all children 1 year of age and older is now recommended. Hepatitis A vaccine, in addition to immunoglobulin, should be considered for staff and residents in an institutional setting where an outbreak of hepatitis A is occurring. An unimmunized 2-year-old child who lacks a history of varicella or herpes zoster diagnosed by a health-care professional, should also receive varicella vaccine. MCV4 is only recommended for children in the age group 2-10 years with a high-risk condition.


SUGGESTED READING

Pickering LK, Baker CJ, Kimberlin DW, Long SS. Red Book2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

Robinson J. Infectious diseases in schools and childcare facilities. Pediatr Rev. 2001;22:39-46.

CASE 97: A 3-YEAR-OLD WITH A FEBRILE SEIZURE

You are called during the middle of a busy day at the office on a Friday afternoon by the pediatric resident at the children’s hospital emergency department. You have been very busy all week, seeing many children of all ages with fever associated with upper respiratory tract symptoms (especially cough, rhinorrhea, and sore throat). The pediatric resident tells you that one of your patients, a 3-year-old previously healthy child, was brought to the emergency department after being witnessed by parents at home to have a 5- to 10-minute episode of shaking of the arms and legs. The shaking of the arms and legs had stopped while en route to the emergency department with the parents.

At the emergency department the child was noted to be sleepy and nonresponsive. The temperature was 103.1°F (39.5°C). There was minimal nasal congestion. The throat was erythematous. The neck was supple; bilateral anterior cervical adenopathy was present. The spleen tip was palpable. Examination of both lungs and the heart were normal.

SELECT THE ONE BEST ANSWER

1. Because it is December and you have been seeing many children with febrile respiratory illnesses in your office, you suspect influenza is the etiology. The most rapid and sensitive method to diagnose influenza A infection is

(A) viral culture of nasopharyngeal specimen

(B) Influenza A EIA antigen detection on throat specimen

(C) Influenza A DFA on nasopharyngeal specimen

(D) Influenza A IgM serology on acute serum

(E) Influenza A (immunochromatographic rapid antigen) test on nasopharyngeal specimen

2. The evaluation for influenza A in the child with the febrile seizure does not confirm that diagnosis. You next consider adenovirus in the differential diagnosis. The best method to diagnose adenovirus includes

(A) “shell vial” culture of nasopharyngeal specimen

(B) polymerase chain reaction (PCR) on nasopharyngeal specimen

(C) adenovirus DFA on nasopharyngeal specimen

(D) adenovirus complement fixation (IgG) antibody on convalescent serum

(E) adenovirus neutralizing (IgG) antibody on acute and convalescent serum

3. While hospitalized the child develops prominent respiratory symptoms, including cough, rhinorrhea, and wheezing, which is noted on physical examination. You now suspect that the child has RSV infection. The diagnostic test of choice for diagnosing RSV is

(A) enzyme immunoassay of nasal wash specimen

(B) enzyme immunoassay of nasal swab specimen

(C) virus isolation of nasopharyngeal aspirate specimen

(D) immunofluorescent assay of throat specimen

(E) PCR of nasopharyngeal aspirate

4. You ask the clinical microbiologist about antimicrobial susceptibility testing of bacteria isolated from clinical specimens of children at the children’s hospital where you practice. You are told there are difficulties in detecting which organism in the microbiology laboratory?

(A) penicillin-resistant Streptococcus pneumoniae

(B) vancomycin-resistant Enterococcus faecium

(C) clindamycin-resistant methicillin-susceptible S aureus

(D) Extended-spectrum beta-lactamase (ESBL) producing Escherichia coli

(E) none of the above; all these choices have become easy to detect

5. A 15-month-old boy presents with a 3-day history of fever to 103°F (39.4°C) followed by refusal to walk. On physical examination he is found to have swelling of the left knee. Arthrocentesis of the left knee reveals purulent fluid that grows S pneumoniae. The minimum inhibitory concentration (MIC) of the organism is 1.0 μg/mL. The organism is nonsusceptible to penicillin with intermediate resistance. The MIC for the S pneumoniae isolate to be considered susceptible to ceftriaxone would be

(A) 0.5 μg/mL or less

(B) 1.0 μg/mL or less

(C) more than 1.0 ug/mL

(D) 2.0 μg/mL

(E) 4.0 μg/mL or more

6. A 2-year-old previously healthy boy develops orbital cellulitis with a positive blood culture for methicillin-resistant S aureus (MRSA). The child is treated with vancomycin at an initial dose of 40 mg/kg per day in 3 divided doses, and serum concentrations of vancomycin are monitored. Adverse reactions to vancomycin include all but

(A) renal toxicity

(B) red-man syndrome

(C) hypotension

(D) dose-related anemia with reticulocytopenia

(E) A and C

7. All but one of the following antibiotics are best monitored by both peak and trough measurements of serum concentrations

(A) amikacin

(B) linezolid

(C) tobramycin

(D) gentamicin

(E) none of the above

8. An 18-month-old boy with recurrent otitis media develops fever, rhinorrhea, and fussiness. At your office he has purulent drainage from the left ear, which you send to the children’s hospital microbiology laboratory for bacterial culture. Amoxicillin is prescribed, and 2 days later you receive a call from the microbiology laboratory that the culture is positive for H influenzae. The method to determine whether or not the isolate is susceptible to amoxicillin is to

(A) perform a test for detection of beta-lactamase production

(B) perform a disk diffusion (Kirby-Bauer) antibiotic susceptibility test

(C) perform the oxacillin disk diffusion test

(D) perform susceptibility testing by the antibiotic gradient method (E-test)

(E) measure the MIC of amoxicillin

9. A 14-year-old adolescent boy who works on a dairy farm presents with a 4-day history of fever, headache, myalgias of the calf, and abdominal pain. On physical examination he is febrile to 102°F (38.8°C) and also has a conjunctival effusion without purulent drainage. You suspect leptospirosis. The most appropriate diagnostic test to perform to confirm the diagnosis is

(A) blood culture

(B) urine culture

(C) anaerobic swab culture of the conjunctiva

(D) PCR test on blood

(E) serology for Leptospira species

10. An 8-year-old girl develops monoarticular arthritis of the left knee 3 months after traveling with her family in Wisconsin. You suspect late disseminated disease manifesting as Lyme arthritis. Of the following, the most accurate statement about the diagnosis of Lyme disease is

(A) the EIA is usually positive in patients with erythema migrans

(B) a positive EIA in a patient with chronic fatigue syndrome is indicative of late disseminated Lyme disease

(C) virtually all patients with late disseminated Lyme disease have IgG antibodies to Borrelia burgdorferi

(D) the EIA if positive should be confirmed by the PCR assay

(E) the diagnosis of early localized disease in the form of erythema migrans is best made by culture of a skin biopsy specimen

11. A 24-year-old woman has a pregnancy complicated by fever, headache, and lymphadenopathy during the first trimester. The mother reports that a number of stray cats live in the neighborhood. The infant is born at 38 weeks’ gestation and weighs 2.5 kg. On physical examination the infant has jaundice, hepatomegaly, chorioretinitis, and scattered punctate calcifications throughout the brain on computed tomography (CT) scan. The diagnostic test to determine the etiology of this infant’s infection is

(A) herpes simplex virus serology on the infant

(B) Toxoplasma gondii serology on the maternal and infant sera

(C) culture of blood and cerebrospinal fluid for lymphocytic choriomeningitis virus

(D) cytomegalovirus (CMV) serology on maternal and infant sera

(E) serologic testing for HIV

12. A 3-month-old female infant is brought to your office by her mother for evaluation of fever, nasal congestion, and poor feeding. On physical examination the infant has a temperature of 101°F, a maculopapular rash, and hepatosplenomegaly. The mother’s obstetric record is not available. You suspect congenital syphilis. The following diagnostic test result would be most useful in confirming infection with Treponema pallidum

(A) a positive Treponema pallidum particle agglutination (TP-PA) test or positive fluorescent treponemal antibody absorption (FTA-ABS) test

(B) a titer of 1:2 on a rapid plasma reagin (RPR) test

(C) a hemoglobin concentration of 7.5 g/dL

(D) the presence of intracranial calcifications

(E) an elevated immunoglobulin M (IgM) level

13. A 4-year-old boy has a 3-day history of mild headache and decreased activity. This is followed by fever to 103°F (39.4°C), mild cough, and sore throat. On physical examination the child has anterior and posterior cervical lymphadenopathy and splenomegaly. The white blood cell count is 5000/mmwith a normal differential. The alanine aminotransferase level is increased at 280 U/L. Of the following, the most diagnostic study is

(A) IgM for hepatitis A in serum

(B) IgM for the viral capsid antigen (VCA) of Epstein-Barr virus

(C) rapid heterophil slide test (monospot)

(D) isolation of HHV-6 from peripheral blood lymphocytes

(E) urine “shell vial” culture for CMV

14. A 14-day-old term infant develops fever to 100.8°F (38.2°C), poor feeding, and two vesicular-appearing skin lesions on the right arm. You suspect neonatal herpes simplex virus (HSV) infection. The most appropriate diagnostic test to perform is

(A) direct fluorescence antibody (DFA) test of skin lesions

(B) Tzanck test of the skin lesions

(C) PCR of skin lesions

(D) serum for type-specific HSV-2 IgG antibody

(E) serum for HSV immunoglobulin M (IgM) antibody

15. Of the following viruses, the one(s) that can be identified by culture is (are)

(A) calicivirus

(B) measles

(C) parvovirus B19

(D) hepatitis E

(E) A and C

16. An 8-year-old girl who has received Bacille Calmette-Guérin (BCG) vaccine at age 5 years now has a positive tuberculin skin test measured using 5 tuberculin (TU) of purified protein derivative. Which of the following would most support that the positive tuberculin skin test (TST) is caused by BCG?

(A) TST of 16 mm induration

(B) known contact with a person with contagious tuberculosis

(C) chest radiographic findings of hilar adenopathy

(D) child’s mother known to have HIV infection

(E) identification of the BCG immunization scar

17. A previously healthy 5-year-old boy has been exposed to Mycobacterium tuberculosis by his aunt who is now hospitalized with cavitary pulmonary tuberculosis. You place a Mantoux test and order a chest radiograph. The Mantoux test is nonreactive, but the chest radiograph is abnormal showing mediastinal adenopathy with a left upper lobe segmental lesion. The most likely explanation for the negative Mantoux skin test is

(A) receipt of measles vaccine 16 weeks earlier

(B) malnutrition

(C) selective anergy to PPD

(D) the child’s young age

(E) underlying immunodeficiency

18. A 3-year-old girl has a large left minimally tender, anterior cervical triangle lymph node that has been present for approximately 5 weeks. All but one of the following factors would suggest a nontuberculosis mycobacterium (NTM) infection

(A) bilateral location of lymphadenopathy

(B) Mantoux test smaller than 12 mm in induration

(C) normal chest radiograph

(D) age younger than 6 years

(E) lack of systemic symptoms, such as fever and weight loss

ANSWERS

1. (C) The rapid antigen tests commercially available for identification of influenza A or B have variable sensitivity and specificity compared with viral culture. The DFA is more sensitive than the rapid antigen tests and its sensitivity is high (90%) when compared with culture. Serologic testing with acute and convalescent serum can identify children with influenza not detected by other methods but is not helpful for rapid diagnosis.

2. (A) The so-called “shell vial” culture is the preferred method of diagnosis of adenovirus infection and can detect virus in culture as early as 2 days. The DFA of nasopharyngeal secretions lacks sensitivity (<70%) as does measurement of complement fixation antibodies. The one exception to viral culture is the detection of the enteric adenovirus types 40 and 41 that cannot be isolated in standard cell cultures. An enzyme immunoassay as well as PCR can be used to detect these enteric adenoviruses in fecal specimens. PCR to diagnose adenovirus from respiratory specimens also has recently been developed.

3. (E) PCR has become the diagnostic test of choice. The enzyme immunoassay of nasal specimens also has advantages including ease of performance, low cost compared with culture, technical simplicity, and short time to a result compared with immunofluorescence assays. The nasal wash is the preferred specimen for diagnostic testing with a higher yield than specimens obtained by swabs.

4. (E) Extended-spectrum beta-lactamase producing E coli were once somewhat difficult to detect in the laboratory, but with modern technique, can now be detected with relative ease. This is related to the difficulty in identifying those organisms that produce these beta-lactamases. Currently, isolates of these species that have MICs of 2 μg/mL or more to cefpodoxime, ceftazidime, cefotaxime, or ceftriaxone should be considered possible ESBL producers.

5. (B) For treatment of nonmeningeal infections caused by penicillin nonsusceptible S pneumoniae isolates, the organism is considered susceptible to ceftriaxone if the MIC is 1.0 μg/mL or less. For treatment of meningeal infections, the breakpoint for ceftriaxone susceptible is 0.5 μg/mL or less (Table 97-1).

TABLE 97-1 Interpretation of Susceptibility Testing for Streptococcus Pneumoniae to Antimicrobial Agents

 
   

NONSUSCEPTIBLE (MIC, μg/mL)

DRUG

SUSCEPTIBLE (MIC, μg/mL)

INTERMEDIATE

RESISTANT

 

Penicillin

≤0.06

0.12-1.0

≥2.0

Amoxicillin

≤2.0

4.0

≥8.0

Cefotaxime/ceftriaxone

     

Meningeal

≤0.5

1.0

≥2.0

Nonmeningeal

≤1.0

2.0

≥4.0

 

Abbreviation: MIC, minimum inhibitory concentration.

6. (D) Anemia is not an adverse reaction associated with vancomycin. Dose-related anemia with reticulocytopenia is an adverse reaction reported commonly with chloramphenicol. This red-man syndrome results in flushing of the upper part of the body during rapid IV infusion of vancomycin.

7. (C) Linezolid does not require measurement of serum concentrations during therapy. Nonrenal pathways account for more than 80% of total body clearance, and only minor age-related changes in clearance have been observed in children of varying ages.

8. (A) Beta-lactamase production is the most frequent mechanism of ampicillin resistance with Haemophilus species and can be rapidly detected in the laboratory. The same test can be used to detect penicillin resistance in Neisseria gonorrhoeaeH influenzae strains are not susceptible to oxacillin. Kirby-Bauer susceptibility testing takes several days.

9. (E) Isolation of Leptospira from blood or CSF specimen can be very difficult, requiring special media, techniques, and long incubation times. Serology is the method of choice for diagnosis, with the macroscopic slide agglutination test the most useful serologic test for screening. Antibodies usually develop during the second week of illness.

10. (C) Localized erythema migrans usually occurs 1-2 weeks after a tick bite so antibodies against Borrelia burgdorferi will not be detectable. IgM antibodies appear 3-4 weeks after infection begins and peak by 6-8 weeks. Specific IgG antibodies usually appear 4-8 weeks after onset of infection and peak 3-6 months later. The EIA test should be corroborated with the Western immunoblot test. The practice of ordering serologic tests for patients with nonspecific symptoms such as chronic fatigue or arthralgia is not recommended.

11. (B) The newborn infant most likely has toxoplasmosis. Serologic tests are the primary approach to the diagnosis of congenital toxoplasmosis. It is important to send blood specimens to a reference laboratory with expertise in performing toxoplasma neonatal serologic assays with interpretive expertise. HSV and CMV are best diagnosed by culture. The diagnosis of lymphocytic choriomeningitis virus is best made by serology, but virus isolation is possible.

12. (A) The clinical picture is highly suggestive. The nontreponemal tests for syphilis (RPR, Venereal Disease Laboratory Test [VDRL]) are sensitive but can produce false-positive results. The treponemal tests (TP-PA, FTA-ABS) are more specific, and a positive TP-PA would confirm the diagnosis of congenital syphilis. Antibody tests including TP-PA and FTA-ABS should be interpreted with caution because the presence of an antibody in a neonate may represent passive transfer.

13. (B) This child most likely has acute EBV infection. Children younger than 5 years with acute EBV infection often have results for heterophil antibody tests that are negative. With acute EBV infection VCA-IgM and VCA-IgG will be positive and serum antibody to the EBV nuclear antigen (EBNA) will be negative. IgM for hepatitis A would be diagnostic but that disease more often presents with clinically apparent jaundice. HHV-6 infection is usually associated with a rash. CMV can cause a “mono” syndrome but a urine culture is not diagnostic.

14. (A) Diagnostic techniques such as the HSV DFA of skin lesions have the advantage of a rapid turnaround time. This technique is as specific but slightly less sensitive than viral culture. For the diagnosis of neonatal HSV infection, specimens for culture should also be obtained from skin vesicles, mouth or nasopharynx, eyes, urine, blood, stool or rectum, and cerebrospinal fluid (CSF). The Tzanck test (examination for multinucleated giant cells and eosinophilic intranuclear inclusions) has lower sensitivity. The CSF should be tested for the presence of HSV DNA by PCR.

15. (B) Of the viruses listed, only measles can be diagnosed by culture, although the simplest method of establishing the diagnosis of measles is by testing for the presence of measles immunoglobulin IgM antibody on a serum specimen obtained during acute illness. Calicivirus and hepatitis E can be diagnosed with a reverse-transcriptase-polymerase chain reaction (RT-PCR) assay for detection of viral RNA in stool as well as by serology. Parvovirus B19 can be diagnosed by serology or PCR assay.

16. (E) Vaccination with BCG vaccine can acutely result in a positive TST. However, the interpretation of TST results among BCG recipients should be the same for people who have not received BCG vaccine. The 16 mm induration, abnormal chest radiograph, and contact with an adult who has a risk factor (HIV) for tuberculosis make it likely that current tuberculosis infection is the cause of the positive TST. The presence of a BCG scar implies vaccine receipt but should not be used to aid in TST interpretation.

17. (C) A negative Mantoux test does not exclude the diagnosis of tuberculosis disease such as pulmonary tuberculosis or latent tuberculosis infection (LTBI). Approximately 10% of immunocompetent children with culture-proven tuberculosis do not react initially to a Mantoux test. Young age (<1 year), malnutrition, and receipt of measles vaccine can increase the likelihood for a negative Mantoux test. The effect of measles vaccine on tuberculin reactivity is temporary and should not last for more than 4-6 weeks after vaccination.

18. (A) All of the factors noted except bilateral location of lymphadenopathy are more likely associated with nontuberculous mycobacterial species. Adenitis due to NTM is usually unilateral and most commonly involves a submandibular node or an anterior superior cervical node.


SUGGESTED READING

Christenson JC, Korgenski EK. Laboratory diagnosis of infection because of bacteria, fungi, parasites and rickettsiae. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008: 1341.

Pickering LK, Baker CJ, Kimberlin DW, Long SS. Red Book 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

CASE 98: A 9-MONTH-OLD WITH FEVER AND CEREBROSPINAL FLUID PLEOCYTOSIS

A 9-month-old male infant was seen by his pediatrician 7 days before admission to the hospital with fever to 101.3°F (38.5°C) and runny nose. He was diagnosed with an uncomplicated viral upper respiratory tract infection and sent home. Two days later the infant was brought to the children’s hospital emergency department because of persistent fever. At that time he was diagnosed with bilateral otitis media, prescribed amoxicillin, and sent home. No laboratory workup was done at the time. Amoxicillin was given as prescribed for the next 5 days, but the patient continued to be febrile. His appetite and activity level decreased. So the parents brought him back to the emergency department the next day.

On physical examination the infant was noted to be irritable. Both tympanic membranes were dull gray with decreased mobility. Nuchal rigidity was present. Examination of the lungs, heart, and abdomen were normal. A spinal tap was performed with these results: WBC 1200/mm(S-65, L-30, M-5), RBC 10/mm3, glucose 10 mg/dL, and protein 100 mg/dL.

SELECT THE ONE BEST ANSWER

1. The Gram stain of the CSF shows gram-positive diplococci, and the culture of the CSF grows S pneumoniae (Figure 98-1). The MIC of penicillin is 0.1 μg/mL and of cefotaxime is 0.25 μg/mL. The appropriate antibiotic therapy for treatment of this infection is

(A) ceftriaxone

(B) chloramphenicol

(C) penicillin G

(D) rifampin

(E) vancomycin

2. You are asked about the indications for different formulations of penicillin (pen) including Pen V, procaine pen G, and benzathine pen G. Procaine pen G is appropriate for treatment of which of the following infections?

(A) congenital syphilis in a neonate

(B) group A streptococcal pharyngitis in a schoolage child

(C) actinomycosis in an adolescent

(D) nosocomial urinary tract infection caused by Enterococcus faecalis in a hospitalized 3-yearold child

(E) Group B streptococcal meningitis in a neonate

art

FIGURE 98-1. Gram stain of CSF that grew S pneumoniae revealing gram-positive diplococci. Note halo surrounding some of the organisms that represents the capsule. See color plates.


3. The penicillinase-resistant penicillin oxacillin is not inactivated by the action of the bacterial penicillinase. Oxacillin would therefore be effective therapy for treatment of which of the following infections?

(A) Enterococcus faecalis bacteremia

(B) Pasteurella multocida wound infection caused by a cat bite

(C) methicillin-susceptible S aureus cellulitis of the lower leg

(D) methicillin-resistant coagulase-negative staphylococci causing a ventriculoperitoneal shunt infection

(E) E coli urinary tract infection

4. Ampicillin is appropriate therapy for which of the following infections?

(A) beta-Lactamase producing Moraxella catarrhalis (B) ESBL-producing Klebsiella pneumoniae (C) MSSA causing pneumonia in a 12-month-old child

(D) Clostridium difficile causing diarrhea in a 4-year-old hospitalized child

(E) Listeria monocytogenes causing meningitis in a 3-week-old infant

5. A 3-year-old child recently diagnosed with acute myelogenous leukemia (AML) has received induction chemotherapy. The child is admitted to the children’s hospital because of fever, neutropenia, and hypotension. The best initial empirical antimicrobial therapy would include

(A) ceftazidime

(B) ceftriaxone and tobramycin

(C) clindamycin and ceftriaxone

(D) vancomycin

(E) ampicillin and gentamicin

6. A 6-week-old infant presents to your office with the insidious onset of cough and tachypnea. On examination the infant is afebrile with rales on pulmonary auscultation. You suspect Chlamydia trachomatis pneumonia that is supported by a chest radiograph demonstrating interstitial infiltrates. Erythromycin is prescribed and you tell the infant’s mother that the most common adverse reaction of erythromycin is

(A) cholestatic jaundice

(B) gastrointestinal (GI) discomfort

(C) hearing loss

(D) maculopapular rash

(E) infantile hypertrophic pyloric stenosis

7. Of the following situations, azithromycin would be most appropriate for treatment of which infection?

(A) a 5-year-old boy with group A streptococcal pharyngitis

(B) a 2-year-old with impetigo caused by MRSA

(C) a 4-year-old child with lobar pneumonia caused by S pneumoniae that is resistant (MIC = 2.0 μg/mL) to penicillin

(D) a 15-year-old adolescent girl with C trachomatis cervicitis

(E) a 6-year old girl with Pseudomonas aeruginosa urinary tract infection

8. An 18-month-old boy develops anterior cervical lymphadenitis requiring drainage of an abscess that has formed. The abscess culture grows MRSA that is D-test negative. The most appropriate antibiotic for treatment would include

(A) vancomycin

(B) imipenem

(C) cefepime

(D) cefazolin

(E) clindamycin

9. A 5-year-old boy whom you follow for short bowel syndrome has a central venous catheter infection. He is admitted to the children’s hospital with fever to 104°F (40°C). He is also known to be colonized with MRSA. A central line infection is strongly suspected and vancomycin is started. The blood culture grows vancomycin-resistant E faecalis. Appropriate therapy would now include

(A) linezolid

(B) meropenem

(C) clindamycin

(D) clofazimine

(E) ceftazidime

10. A 13-year-old adolescent boy with HIV infection is being treated with trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jiroveci pneumonia. Adverse reactions that can occur during TMP-SMX therapy include all but

(A) Stevens-Johnson syndrome

(B) neutropenia

(C) renal dysfunction

(D) pancreatitis

(E) diarrhea

11. Sulfonamides such as sulfadiazine, sulfamethoxazole, and sulfisoxazole all have indications for clinical use in infants and children for all of the following except

(A) congenital toxoplasmosis

(B) prophylaxis of urinary tract infections

(C) ulcerative lesions caused by Nocardia

(D) meningitis caused by Neisseria meningitidis

(E) chlamydial conjunctivitis

12. A 21/2-year-old girl with a ventriculoperitoneal shunt placed after an intraventricular hemorrhage (IVH) occurring as a premature neonate develops fever to 102.2°F (39°C), vomiting, and irritability. Examination of the CSF reveals pleocytosis and a Gram stain showing a few gram-positive cocci in clusters. You start empirical therapy with vancomycin. All of the following are appropriate uses of vancomycin except

(A) treatment of serious infections attributable to beta-lactam-resistant gram-positive organisms

(B) treatment of infections attributable to grampositive microorganisms in patients with serious allergy to beta-lactam agents

(C) empiric antimicrobial therapy for a febrile neutropenic patient

(D) prophylaxis for major surgical procedures involving implantation of prosthetic materials or devices at institutions with a high rate of infection caused by MRSA

(E) treatment of Clostridium difficile colitis that fails to respond to metronidazole therapy

13. A 5-year-old boy from New York comes to your office with a swollen, tender left knee and some limitation of motion. His mother remembers the child having been bitten by a tick a few months ago during the summer. You suspect Lyme disease, which is confirmed by serology. The mother was treated for Lyme disease 2 years ago with doxycycline and wonders if her child should also be treated with doxycycline. You tell her that

(A) doxycycline is only indicated for early Lyme disease with erythema migrans

(B) ceftriaxone is the antibiotic of choice for initial treatment of Lyme arthritis in children

(C) doxycycline can cause permanent dental discoloration in children younger than 8 years

(D) doxycycline is the antibiotic of choice if the arthritis does not initially respond to treatment with amoxicillin

(E) doxycycline is the recommended treatment if Lyme disease is complicated by meningitis

14. A 4-year-old child with Streptococcus viridans group endocarditis is being treated with penicillin and gentamicin. The following statement best describes the nephrotoxicity caused by the use of aminoglycosides

(A) aminoglycosides vary markedly in their risk for nephrotoxicity

(B) nephrotoxicity can be increased by the concomitant use with cyclosporine

(C) the dose of aminoglycosides is not correlated with development of nephrotoxicity

(D) gentamicin nephrotoxicity is usually irreversible

(E) nephrotoxicity is not related to the duration of aminoglycoside exposure

15. A 4-year-old girl returns from a trip to Pakistan with her family. She develops fever, headache, and abdominal pain that persists for 1 week. She has mild intermittent diarrhea and a rash develops in the second week of the illness. Salmonella typhi is isolated from blood that is ampicillin resistant but chloramphenicol susceptible. The most common adverse effect occurring with chloramphenicol use includes

(A) gray baby syndrome

(B) aplastic anemia

(C) ototoxicity

(D) myocardial toxicity

(E) dose-dependent anemia with low reticulocyte count

16. The use of fluoroquinolones in the pediatric age group has been limited because fluoroquinolones cause cartilage damage in puppies and large joint arthropathy in other immature animals. Their use in children therefore has not been approved by the FDA except for ciprofloxacin, which has been approved for complicated urinary tract infections, pyelonephritis caused by E coli, and postexposure prophylaxis for inhalation anthrax. Nevertheless, there has been an increasing experience in children with the use of fluoroquinolones in certain situations. Which of the following scenarios is a clinical situation in which the use of a fluoroquinolone is inappropriate?

(A) pulmonary exacerbation in cystic fibrosis patient

(B) cellulitis caused by MRSA

(C) typhoid fever caused by S typhi resistant to ampicillin, ceftriaxone, and TMP-SMX

(D) urinary tract infection caused by Pseudomonas aeruginosa

(E) part of an initial multidrug regimen for inhalational anthrax

17. A 4-year-old girl has had daily contact with her aunt for the past 2 months. The aunt has recently been diagnosed with isoniazid-resistant pulmonary tuberculosis. A chest radiograph of the child is normal. Appropriate treatment of the child includes

(A) azithromycin

(B) ethambutol

(C) rifampin

(D) clofazimine

(E) linezolid

18. A 6-year-old boy develops an intra-abdominal abscess following appendectomy for a ruptured appendix. Meropenem is being administered as part of empiric therapy. Organisms that are susceptible to meropenem include

(A) Stenotrophomonas maltophilia

(B) MRSA

(C) penicillin-resistant Streptococcus pneumoniae

(D) Serratia marcescens

(E) A and C

ANSWERS

1. (A) There is a difference in the susceptibility break points for ceftriaxone and cefotaxime for meningeal versus nonmeningeal infections. For meningeal isolates, the MIC of ceftriaxone must be 0.5 μg/mL or less to be considered susceptible. For nonmeningeal isolates, the susceptibility break point is 1.0 μg/mL or less. Thus the meningeal isolate is susceptible to ceftriaxone.

2. (A) There are a number of formulations of penicillin. Benzathine penicillin by IM injection can be used for the treatment of group A streptococcal pharyngitis. Actinomycosis is best treated initially with IV penicillin G. E faecalis causing a urinary tract infection is usually treated with oral amoxicillin or IV ampicillin. Procaine penicillin G is sometimes used to treat congenital syphilis.

3. (C) The penicillinase-resistant penicillin oxacillin is active against MSSA. Enterococci and gramnegative bacilli (including Pasteurella species) and methicillin-resistant coagulase-negative staphylococcal infections cannot be treated with semisynthetic penicillins.

4. (E) Ampicillin is considered a preferred antimicrobial agent for treatment of Listeria infections. Bacteria that produce beta-lactamase are resistant to ampicillin because the enzyme hydrolyzes the beta-lactam antibiotic. Staphylococcal resistance to ampicillin is also mediated through production of penicillinase. C difficile pseudomembranous colitis can occur after treatment with ampicillin, as it can after most antibiotics.

5. (A) In this clinical situation infection with Pseudomonas aeruginosa is a major concern. Ceftazidime, a third-generation cephalosporin, is active against most pseudomonas strains. Its low toxicity makes it an appealing choice for this situation. Tobramycin- or gentamicin-containing regimens are also generally active against pseudomonas. But they have the disadvantage of greater toxicity as well as the need to monitor blood levels.

6. (B) The most common adverse effect of erythromycin is GI discomfort and nausea. A rare association between oral erythromycin and infantile hypertrophic pyloric stenosis has been reported in infants younger than 6 weeks of age. Azithromycin also is a recommended antimicrobial agent for the treatment of chlamydia pneumonia.

7. (D) Azithromycin can be used for treatment of uncomplicated Chlamydia cervicitis (single 1-g oral dose). MRSA strains are almost always resistant to macrolides like azithromycin. A high percentage (>75%) of penicillin-resistant S pneumoniae isolates are also resistant to azithromycin.

8. (E) The MRSA isolate is erythromycin resistant and clindamycin susceptible, so the D-test was performed. The D-test is used to screen for the presence of the erythromycin ribosomal methylase (erm) gene. If the D-test is positive, it suggests the presence of the erm gene in the S aureus isolate. In this instance, treatment of the S aureus infection with clindamycin can select for mutants during therapy that are also clindamycin resistant. Because the D-test is negative this risk does not exist.

9. (A) Linezolid is an oxazolidinone antibiotic that binds the 50S ribosomal subunit and inhibits protein synthesis. Linezolid is active against MRSA, vancomycin-resistant enterococci (VRE), and penicillin-resistant S pneumoniae. The other choices are inactive against this isolate.

10. (D) The most common adverse events are GI (nausea and vomiting) and skin reactions. Adverse reactions to TMP-SMX occur infrequently in non-AIDS patients (<5%) but frequently (15%) in children with AIDS. The most common adverse event in children with AIDS is an erythematous maculopapular rash that is often transient and can clear without stopping the drug.

11. (D) Sulfonamides are not recommended for treatment of meningococcal meningitis but were once used to successfully treat meningitis caused by Salmonella and Listeria. Sulfonamides are useful for the treatment of urinary tract infections and pyelonephritis, gastroenteritis when caused by susceptible strains of Shigella, and in the treatment of infections caused by Nocardia.

12. (C) The Centers for Disease Control and Prevention (CDC) has established guidelines for situations in which the use of vancomycin is appropriate as well as situations in which the use of vancomycin is discouraged (Table 98-1). Vancomycin is not recommended for initial empiric therapy of a patient with fever and neutropenia.

13. (C) Tetracyclines can combine with newly formed bone to produce a tetracycline-calcium orthophosphate complex that can inhibit bone growth in neonates and cause staining of the enamel of the teeth in children younger than 8 years. For this 5-year-old child the treatment of choice for Lyme arthritis would be amoxicillin for a 28-day course (compared with amoxicillin for 14-21 days for early localized disease). For persistent or recurrent arthritis, the treatment of choice would be ceftriaxone.

TABLE 98-1 Situations in Which Vancomycin Use Should be Discouraged

 

Routine surgical prophylaxis (exception: life-threatening allergy to beta-lactam antibiotics)

Empiric antimicrobial therapy for febrile neutropenic patients

Treatment of a single positive blood culture for coagulase-negative staphylococcus if other blood cultures taken around the same time are negative

Continued empiric use for presumed infections with no evidence of beta-lactam-resistant gram-positive bacteria

Selective decontamination of GI tract

Attempted eradication of MRSA colonization

Primary treatment of non-life-threatening antibiotic-associated colitis

Treatment of any infection caused by beta-lactam-susceptible gram-positive bacteria

Topical application or irrigation

 

Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.

14. (B) Gentamicin nephrotoxicity is characterized by proximal tubular necrosis in the kidneys. Risk factors for nephrotoxicity from aminoglycosides include high dose, prolonged course, liver disease, concomitant use of other nephrotoxic drugs such as cyclosporine, and salt and water depletion (such as dehydration or sepsis).

15. (E) Bone marrow suppression can occur with chloramphenicol in two ways. The first is related to the duration of the dose and is reversible. It is usually seen after 7 days of therapy and manifests as anemia with a low reticulocyte count. It is associated with peak and trough serum chloramphenicol concentrations greater than 25 and 10 μg/mL, respectively. Chloramphenicol can also cause idiosyncratic aplastic anemia that is irreversible and occurs in about 1 in 40,000 patients treated. This is similar to the rate of fatal anaphylaxis with beta-lactams such as penicillins and cephalosporins.

16. (B) Use of the fluoroquinolones is still generally contraindicated in children and adolescents younger than 18 years of age. There are certain situations in which fluoroquinolones may be useful including when no other oral agent is available or the infection is caused by a multidrug-resistant gramnegative enteric bacterium such as Pseudomonas aeruginosa. MRSA are often fluoroquinolone resistant; resistance to them may develop rapidly. For community-associated MRSA infections in children, there are alternative antibiotics.

17. (C) Rifampin has been used alone for the treatment of latent tuberculosis infection in infants, children and adolescents when isoniazid (INH) could not be tolerated, or the index case was infected with an INH-resistant, rifampin-susceptible organism. In this clinical situation rifampin should be given for at least 6 months. Patients should be informed that rifampin can cause orange urine, sweat, and tears and discoloration of soft contact lenses. Sexually active women on oral contraception should be informed that rifampin can make oral contraceptives ineffective.

18. (D) Meropenem is a carbapenem antibiotic that has a broad spectrum of activity against many grampositive aerobic cocci, gram-negative enteric bacteria, and anaerobes. In this example, meropenem would likely be active against Serratia marcescens but not against MRSA. Stenotrophomonas maltophilia is commonly resistant to the carbapenems. Another carbapenem antibiotic, imipenem-cilastin, has been associated with an increased risk of seizures. This risk appears to be related to high dose, age (elderly), and impaired renal function.


SUGGESTED READING

Bradley JS, Sauberan J. Antimicrobial agents. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008: 1420.

Jacob RF. Judicious use of antibiotics for common pediatric respiratory infections. Pediatr Infect Dis J. 2000;19:938-943.

CASE 99: AN 18-MONTH-OLD WITH FEVER AFTER RENAL TRANSPLANT

An 18-month-old boy whom you have followed in your practice since birth was diagnosed with renal failure secondary to posterior urethral valves. As a result he underwent a renal transplant with success. Renal function post-transplant has been normal, and he is receiving a number of immunosuppressive medications to prevent rejection of the transplanted kidney. One month after the kidney transplant, he develops fever associated with cough and rhinorrhea.

On physical examination the child is sitting up in his mother’s lap. He is alert and active. The temperature is 101.4°F (38.6°C). There is clear rhinorrhea but no abnormalities of the oropharynx. Lungs and heart examinations are normal. Examination of the abdomen reveals a palpable kidney in the right lower quadrant but no abdominal tenderness. The leukocyte count is 8900/mm(S-20, L-65, M-15), the hemoglobin concentration is 8.0 g/dL, and the platelet count is 120,000/mm3. A chest radiograph reveals no evidence of pneumonia.

SELECT THE ONE BEST ANSWER

1. Before transplant it was known that the child was seronegative for CMV and the donor of the kidney was seropositive. The antiviral agent of choice for prophylaxis of CMV infection is

(A) acyclovir

(B) cidofovir

(C) foscarnet

(D) ganciclovir

(E) zidovudine

2. The mother of the child asks you about adverse effects that can occur with the use of ganciclovir. You tell the mother that the most important toxic effect of ganciclovir is

(A) anemia

(B) neutropenia

(C) hallucinations

(D) hepatitis

(E) renal toxicity

3. The mechanism of action of ganciclovir includes

(A) prevention of viral entry into the host cell

(B) prevention of viral transcription by inhibiting viral DNA polymerase

(C) interrupting viral protein assembly

(D) modulation of host response to infection

(E) inhibition of the reverse transcriptase enzyme

4. An 1800-g infant is born at 35 weeks’ gestation. Growth parameters are consistent with intrauterine growth retardation including microcephaly. The infant has scattered petechiae as well as hepatosplenomegaly. The diagnosis of congenital CMV infection is confirmed by detection of virus in sequential urine specimens. IV ganciclovir is discussed with the parents as a treatment option. The major benefit of IV ganciclovir in this clinical setting is

(A) prevention of sensorineural hearing loss

(B) more rapid resolution of hepatosplenomegaly

(C) more rapid resolution of CMV retinitis

(D) improved weight gain and head circumference growth

(E) more rapid resolution of thrombocytopenia

5. A 3-year-old child is hospitalized for repair of congenital heart disease. Influenza B is known to be present in the community, and there has been influenza B infection in several staff members. The child did not receive influenza vaccine. The best initial management is

(A) initiation of zanamivir chemoprophylaxis

(B) vaccination with whole virus influenza vaccine

(C) vaccination with live attenuated influenza vaccine

(D) initiation of rimantadine chemoprophylaxis

(E) initiation of oseltamivir chemoprophylaxis

6. You are asked about the activity and treatment of antiviral agents against influenza. Which of the following antiviral agents are active against influenza A and influenza B and approved for treatment of infection caused by both viruses?

(A) amantadine

(B) rimantadine

(C) zanamivir

(D) interferon-alpha

(E) ribavirin

7. A 15-year-old adolescent female develops a fever of 104°F (40°C), cough, rhinorrhea, headache, sore throat, and myalgias during the middle of an epidemic of influenza A. You are considering prescribing oseltamivir for treatment. Recommendations for use of oseltamivir include starting the medication within which of the following number of days of symptoms of influenza?

(A) 1 day

(B) 2 days

(C) 3 days

(D) 4 days

(E) 7 days

8. For another patient, you are asked about the potential indications for acyclovir use. The infection for which your patient is most likely to benefit from the use of acyclovir is

(A) a 14-year-old adolescent female with an initial genital herpes infection that began 2 days ago

(B) a 2-week-old female infant with microcephaly, hepatosplenomegaly, and shedding CMV in the urine

(C) a 3-year-old with hepatitis associated with varicella zoster virus infection that began 2 days ago

(D) a 2-year-old boy with encephalitis caused by human HHV type VI

(E) a 15-month old healthy infant with adenovirus pneumonia

9. You are asked about the mechanism of action of acyclovir by a group of medical students. You reply that

(A) acyclovir in its triphosphate form inhibits the viral DNA polymerase of HSV

(B) acyclovir has metabolites that interfere with elongation of viral messenger RNA during HSV infection

(C) acyclovir results in the methylation of viral messenger RNA during HSV infection

(D) acyclovir interferes with viral protein synthesis in HSV

(E) acyclovir inhibits the reverse transcriptase enzyme in HSV

10. The most serious side effect of acyclovir is

(A) acute renal failure

(B) hematuria

(C) neurotoxicity

(D) hypoglycemia

(E) neutropenia

11. You are asked about the appropriate indications for the use of foscarnet. Of the following indications listed, the one in which foscarnet would not be appropriate includes

(A) CMV retinitis in a 19-year-old man with AIDS

(B) CMV infection that is unresponsive to ganciclovir in an 18-month-old child, a renal transplant recipient

(C) primary acyclovir resistant varicella in an 8-year-old girl with ALL

(D) Parainfluenza virus pneumonia in a 12-year-old boy with leukemia

(E) mucocutaneous acyclovir-resistant HSV infection in a 3-year-old child post a stem cell transplant

12. The most common serious adverse effect of foscarnet includes

(A) hypocalcemia

(B) neutropenia

(C) pancreatitis

(D) seizures

(E) nephrotoxicity

13. A 6-year-old Asian boy with perinatal hepatitis B infection has persistent hepatitis B surface antigen (HBsAg) in serum, no hepatitis B surface antibody (Anti-HBs), and a positive hepatitis B e antigen (HBeAg). These findings are consistent with chronic hepatitis B infection. An appropriate antiviral agent for treatment of this infection includes

(A) cidofovir

(B) interferon-alpha

(C) trifluridine

(D) vidarabine

(E) zidovudine

14. The most likely adverse reaction associated with the first week of therapy of the child with chronic hepatitis B infection in the previous question is

(A) influenza-like illness with fever, chills, headache, myalgias, arthralgias

(B) seizures

(C) anemia

(D) renal insufficiency

(E) neutropenia

15. An 8-year-old girl recently diagnosed with HIV infection has a CD4 count of 400/μL. The viral load measured is 100,500 copies/mL. Initial management regarding antiretroviral therapy for children and adolescents with HIV infection can include any of the following except

(A) 2 nucleoside reverse transcriptase inhibitor (NRTIs) plus one PI

(B) 2 NRTIs plus one nonnucleoside reverse transcriptase inhibitor (NNRTI)

(C) 3 NRTIs

(D) 1 NRTI

(E) none of the above

16. Monotherapy with an antiretroviral agent is recommended in which of the following circumstances

(A) 14-year-old adolescent with a CD4 count of 300/μL and suspected poor compliance

(B) newborn infant born to an HIV-positive mother

(C) 6-month-old infant girl with viral load of 50,000 copies/mL and a CD4 count of 750/μL

(D) 10-year-old girl with a newly diagnosed HIV infection, detectable viral load, a CD4 count of 650, and percentage of 33%

(E) a 6-year-old asymptomatic child with a CD4 count of 500/μL and viral load of 10,000 copies/mL

17. The major toxicity associated with zidovudine in children is

(A) anemia

(B) lactic acidosis

(C) pancreatitis

(D) peripheral neuropathy

(E) diarrhea

18. You are considering using a protease inhibitor in a highly active antiretroviral combination regimen for treatment of HIV infection in a pediatric patient. Protease class disadvantages include all but

(A) metabolic complications including dyslipidemia, fat maldistribution, and insulin resistance

(B) higher pill burden than nucleoside or nonnucleoside analog reverse transcriptase inhibitorbased regimens

(C) poor palatability of liquid preparations

(D) common adverse reactions including diarrhea, nausea, and vomiting

(E) resistance that requires only a single mutation in the protease enzyme

ANSWERS

1. (D) For renal transplant recipients, antiviral therapy is recommended when the recipient is seronegative for CMV and the donor is seropositive. If the donor or recipient is seropositive for CMV and antilymphocyte treatment is used, antiviral therapy is also recommended. In one comparative trial of antiviral therapy for CMV prophylaxis among kidney transplant recipients, ganciclovir was superior to acyclovir.

2. (B) Myelosuppression is the most frequent toxic effect of ganciclovir. The incidence of neutropenia is 40%. Thrombocytopenia occurs in 20% of patients and anemia in 2% of ganciclovir recipients. Hallucinations and hepatitis are rare adverse events associated with ganciclovir.

3. (B) Ganciclovir is a nucleoside analog that is phosphorylated first by virus-encoded enzymes and then by cellular enzymes. Ganciclovir triphosphate is a competitive inhibitor of herpes viral DNA polymerase but has some activity against cellular DNA polymerases.

4. (A) A randomized controlled trial of neonates with symptomatic CMV disease involving the central nervous system (CNS) found that neonates treated with 6 weeks of IV ganciclovir prevented hearing deterioration at 6 months of age and may prevent hearing loss at 1 year of age or older. Neutropenia is a significant side effect of the therapy.

5. (E) Chemoprophylaxis for prevention of influenza A and B is indicated to protect high-risk children (eg, patients with congenital heart disease during the 2 weeks after immunization while an immune response is developing or if the child is immunized after influenza is circulating in the community). In addition to receiving oseltamivir for chemoprophylaxis, influenza vaccine should also be administered to a 3-year-old child. Two doses will be required if there is no previous exposure with influenza vaccines. Zanamivir is licensed for prophylaxis against influenza A and B for children 5 years of age and older and oseltamivir for children 1 year of age and older. Awareness of influenza A resistance patterns provided by state and local health departments through the CDC is extremely important in deciding appropriate chemoprophylaxis for influenza.

6. (C) Amantadine and rimantadine are only active against influenza A. Interferon-alpha is not recommended for treatment of influenza. Zanamivir is approved for prophylaxis of influenza A or B in children 5 years of age and older and for treatment of children 7 years of age and older.

7. (B) Based on placebo-controlled studies in both adults and children, patients who receive oseltamivir within 2 days of onset of symptoms of influenza had a shorter illness duration, more rapid return to normal health and activity, and decreased frequency of secondary complications such as sinusitis and otitis media that required antibiotic prescriptions. Therapy should be considered for children at increased risk of severe or complicated influenza, healthy children with severe illness, and for children in special environmental, family, or social situations in which ongoing illness would be detrimental.

8. (A) Patients with the first episode of genital herpes may initially have mild symptoms but develop more severe or prolonged symptoms. Both acyclovir and valacyclovir decrease the duration of symptoms and viral shedding in genital herpes. If oral acyclovir is initiated within 6 days of the onset of disease, the duration of illness and viral shedding are shortened by 3-5 days.

9. (A) Acyclovir is a dioxygenase analog that is monophosphorylated by virus-encoded thymidine kinase and then diphosphorylated and triphosphorylated by host cell enzymes. Acyclovir triphosphate prevents viral DNA synthesis by inhibiting viral DNA polymerase. Acyclovir also results in DNA chain termination.

10. (C) The most frequent neurologic manifestations are tremors, myoclonus, lethargy, agitation, and hallucinations. These side effects occur in patients with compromised renal function who achieve high concentrations of acyclovir. Neutropenia has been observed in neonates receiving high doses of IV acyclovir (60 mg/kg per day) for treatment as well as infants receiving oral acyclovir for suppressive therapy.

11. (D) Foscarnet is a noncompetitive inhibitor of viral DNA polymerase. Foscarnet can be used for treatment of CMV retinitis in patients with AIDS. Foscarnet also is an option for a patient with severe CMV infection that is unresponsive to ganciclovir. Foscarnet also is the antiviral agent of choice for treatment of acyclovir-resistant herpes simplex and varicella zoster infections. Parainfluenza virus is an RNA virus, and foscarnet is not active against RNA viruses.

12. (E) Azotemia, proteinuria, acute tubular necrosis, crystalluria, and interstitial nephritis can occur. Risk factors for renal dysfunction include preexisting renal disease, use of other nephrotoxic drugs, dehydration, rapid injection of large doses, and continuous IV infusion. Hypocalcemia can occur because of chelation of ionized calcium by foscarnet. Seizures are one CNS complication that can occur as a manifestation of hypocalcemia.

13. (B) Interferons are a family of immunoregulatory proteins associated with a variety of antiviral, antiproliferative, and immunomodulatory activities. Interferon-alpha is approved for treatment of chronic hepatitis B and hepatitis C infection as well as papillomavirus-induced anogenital disease.

14. (A) The symptoms of an influenza-like illness usually remit with continued therapy. These symptoms rarely require discontinuing therapy or changing the dose. The two major therapy-limited toxicities of interferon are neuropsychiatric complications (somnolence, confusion, behavioral disturbances, depression, seizures) and bone marrow suppression. Neutropenia and thrombocytopenia commonly occur.

15. (D) Either choice A or B are preferred regimens for initial antiretroviral therapy and would be considered highly active antiretroviral therapy (HAART). This includes at least three drugs for the initial treatment of infants, children, and adolescents with HIV infection. This triple drug regimen should include at least two different classes of antiretroviral medications. Choice C, which is triple NRTI therapy, should only be used in special circumstances. The regimen should be considered only when there is concern regarding drug interactions or adherence (Table 99-1). In infants exposed to nevirapine as a result of maternal-infant prophylaxis, nevirapine is not recommended for initial therapy. Choice D, which is monotherapy, should never be used as therapy for children with HIV infection. Dual therapy with two NRTIs also should never be recommended for initial therapy. If there are significant concerns regarding adherence with antiretroviral medications, these should be addressed first before starting therapy.

16. (B) Monotherapy as initial therapy for HIV infection in children is only recommended for chemoprophylaxis administered to HIV-exposed infants during the first 6 weeks of life to prevent perinatal HIV transmission.

17. (A) The most common toxicities in children with zidovudine treatment are anemia and neutropenia, both of which usually resolve with temporary cessation of drug or dose modification. The NRTI drugs didanosine (ddI) and stavudine (d4T) have peripheral neuropathy as their primary toxicity. Abacavir (ABC) has been associated with a hypersensitivity reaction consisting of fever, rash, nausea, vomiting, or abdominal pain. This reaction should result in permanent discontinuation of the drug.

18. (E) With the protease class inhibitors, resistance requires multiple mutations. The protease inhibitors target HIV during maturation of the virion by inhibiting the viral protease.

TABLE 99-1 Recommended Antiviral Drugs for Initial Therapy of Children with Human Immunodeficiency Virus Infection

 

REGIMENS

PI BASED

NNRTI BASED

NRTI BASED

 

Preferred

2 NRTIs plus lopinavir/ritonavir

≥3 yr: 2 NRTIs plus efavirenz

≤3 yr or can’t swallow capsules:

2 NRTIs plus nevirapine

None

Abbreviations: PI, protease inhibitor; NNRTI, nonnucleoside analog reverse transcriptase inhibitor; NRTI, nucleoside analog reverse transcriptase inhibitor.


SUGGESTED READING

Guidelines for the use of antiretroviral agents in pediatric HIV infection. USDHHS AIDSinfo Web site. http://AIDSinfo.nih.gov. Accessed July 28, 2009.

Kimberlin DW. Antiviral agents. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008: 1470.

CASE 100: A 12-YEAR-OLD GIRL WITH LEUKEMIA AND PERSISTENT FEVER

A 12-year-old girl, whom you have followed in your practice since birth, was recently diagnosed with AML after developing fever, fatigue, and epistaxis. Your patient had begun chemotherapy under the guidance of your pediatric oncology consultant. After induction chemotherapy was completed, you receive a phone call on a Saturday evening that your patient has developed fever at home. You direct your patient’s parents to bring her to the children’s hospital emergency department.

On physical examination at the emergency department, the adolescent girl was nontoxic in appearance. The temperature was 102.2°F (39°C). There was mild erythema of the posterior pharynx. Examination of both lungs and the heart were normal. A WBC count revealed an absolute neutrophil count of 200/mm3, hemoglobin of 9.0 g/dL, and platelet count of 130,000/mm3. Ceftazidime empirical therapy was begun. However, fever persisted, and after 4 days a repeat WBC count revealed an absolute neutrophil count of 0/mm3.

SELECT THE ONE BEST ANSWER

1. The most appropriate course of action to follow with the persistence of fever includes

(A) addition of vancomycin to antibiotic regimen

(B) change of ceftazidime to imipenem

(C) addition of ketoconazole

(D) addition of liposomal amphotericin B

(E) addition of acyclovir

2. One of the common adverse events to monitor now in the 12-year-old patient after the change in management just described is

(A) hypercalcemia

(B) hypokalemia

(C) hypermagnesemia

(D) hyperuricemia

(E) hyponatremia

3. An 850 g very low birthweight infant now 24 days old has a central venous catheter and has completed a 10-day course of broad-spectrum antibiotic therapy with cefotaxime and gentamicin for a bacteremia caused by E coli. The infant develops apnea along with poor feeding and hypothermia. A blood culture sent to the microbiology laboratory is reported in 24 hours to be growing a yeast. Appropriate initial therapy would now include

(A) amphotericin B deoxycholate

(B) fluconazole

(C) liposomal amphotericin B

(D) flucytosine

(E) caspofungin

4. You prescribe griseofulvin for a 6-year-old child with Tinea capitis. Which of the following is not true about griseofulvin?

(A) treatment for 4-6 weeks is the usual regimen

(B) the drug is applied topically to the lesions

(C) prolonged therapy is associated with hepatotoxicity

(D) the drug is given once daily

(E) the drug should be given after a meal containing fat

5. You are asked about the appropriate indications for use of the triazole antifungal agent fluconazole. For which of the following infections would fluconazole be appropriate for first-time therapy?

(A) treatment of esophageal candidiasis caused by Candida albicans in a 6-year-old child with HIV infection

(B) treatment of hepatosplenic candidiasis in a 3-year-old child with AML

(C) a premature neonate with Candida tropicalis fungemia and a renal fungus ball

(D) catheter-associated fungemia with Candida krusei

(E) Tinea capitis in a healthy 8-year-old child

6. The most common adverse reactions reported with the triazoles include

(A) hepatitis

(B) rash

(C) GI symptoms (nausea, vomiting, diarrhea)

(D) fatigue

(E) anemia

7. A 12-year-old adolescent boy has fever, cough, and productive sputum production for 4 weeks. A chest radiograph reveals a right lower lobe infiltrate. A sputum culture grows Blastomyces dermatitis. He is not vomiting and requires no supplemental oxygen. The antifungal agent of choice for treatment of this infection is

(A) fluconazole

(B) terbinafine

(C) ketoconazole

(D) amphotericin B

(E) itraconazole

8. Antifungal therapy is begun and the adolescent develops pedal edema. This finding is most likely an adverse effect associated with

(A) fluconazole

(B) itraconazole

(C) ketoconazole

(D) amphotericin B

(E) nystatin

9. You are asked about the appropriate indications for the use of flucytosine (5-fluorocytosine). You indicate that flucytosine is the preferred treatment for the following infection in combination with amphotericin B

(A) chronic mucocutaneous candidiasis

(B) cryptococcal meningitis

(C) pulmonary aspergillosis

(D) disseminated histoplasmosis

(E) disseminated blastomycosis

10. A 13-year-old adolescent with AML has persistent fever and neutropenia. Pulmonary infiltrates present are suspicious for aspergillus infection. The antifungal agent of choice for treatment of invasive aspergillosis refractory to amphotericin B is

(A) caspofungin

(B) fluconazole

(C) miconazole

(D) flucytosine

(E) voriconazole

11. Itraconazole is the preferred antifungal therapy for moderate pulmonary infections caused by all but one of the following fungi

(A) Histoplasma capsulatum

(B) Cryptococcus neoformans

(C) Blastomyces dermatitidis

(D) Sporothrix schenckii

(E) Coccidioides immitis

12. A 13-year-old girl has developed soft disfigured nails with pits and grooves involving only the nails of her hands. A fungal culture grows Tinea unguium. The antifungal agent of choice for this infection is

(A) fluconazole

(B) griseofulvin

(C) itraconazole

(D) terbinafine

(E) voriconazole

13. The duration of therapy for the 13-year-old adolescent with T unguium in the previous example should be

(A) 6 weeks

(B) 12 weeks

(C) 24 weeks

(D) 36 weeks

(E) 52 weeks

14. A 3-year-old child presents to your office because of persistent itching for the past 2 weeks. On physical examination the child is afebrile. The examination of the skin reveals scattered papules and burrows involving the arms, legs, palms, soles, and the trunk. You make the diagnosis of scabies examining the scrapings of a burrow to which mineral oil is first applied. The treatment of choice for this condition includes

(A) lindane 1% lotion

(B) pyrethrins plus piperonyl butoxide

(C) crotamiton 10% cream

(D) single oral dose of ivermectin

(E) permethrin 5% cream

15. A 3-year-old child develops abdominal pain and diarrhea about 4 weeks after returning with his family from a trip to South America. About 12 weeks later he is diagnosed with iron deficiency anemia and peripheral eosinophilia (20%). Intestinal hookworm infection is detected by identifying the hookworm eggs in feces. You recommend treatment with

(A) albendazole 400 mg in a single dose

(B) mebendazole 100 mg in a single dose

(C) pyrantel pamoate 11 mg/kg per dose (maximum: 1.0 g) for 1 dose

(D) niclosamide 1 g in a single dose

(E) ivermectin 150 μg/kg in a single dose

16. A 2-year-old child returns with her parents from vacation in Southeast Asia. The child presents to your office with abdominal pain and bloody diarrhea with mucus. You diagnose infection with whipworm (Trichuris trichiura) by examination of stool for the characteristics of T trichiura eggs. Treatment of the infection should include

(A) albendazole 400 mg in a single dose

(B) mebendazole 100 mg twice daily for 3 days

(C) pyrantel pamoate 1 g in a single dose

(D) ivermectin 200 μg/kg in a single dose

(E) mebendazole 100 mg in a single dose

17. Metronidazole has both antibacterial and antiprotozoal properties. Major indications for the use of metronidazole include all but

(A) actinomycosis

(B) brain abscess secondary to chronic sinusitis

(C) giardiasis

(D) Trichomonas vaginitis

(E) liver abscess secondary to Entamoeba histolytica

18. A 4-year-old girl is going to travel with her family to West Africa where chloroquine-resistant Plasmodium falciparum is reported. Appropriate chemoprophylaxis for the child would include

(A) doxycycline

(B) atovaquone-proguanil

(C) sulfadoxine-pyrimethamine

(D) clindamycin

(E) chloroquine

ANSWERS

1. (D) Fungi are common causes of secondary infection among neutropenic patients who have received courses of broad-spectrum antibiotic therapy. Fungi can also cause primary infections. Studies have indicated that up to a third of febrile neutropenic patients who do not respond to a 1-week course of antibiotic therapy have a systemic fungal infection.

2. (B) Nephrotoxicity is the most frequent adverse event, which can result in renal tubular acidosis, hypokalemia, hypomagnesemia from its effect on the kidneys as well as anemia. Amphotericin B inhibits erythropoietin production in the kidney resulting in anemia as the cumulative dose increases. The nephrotoxicity of liposomal amphotericin is much lower than that occurring with the nonliposomal form.

3. (A) The premature neonate likely has catheterrelated fungemia caused by Candida. The infant could also have disseminated candidiasis. In both these instances a blood culture will yield Candida. Amphotericin B deoxycholate is the drug of choice for treatment of suspected fungal infections in premature infants. Renal toxicity in this age group with nonliposomal amphotericin is infrequent.

4. (B) Griseofulvin has a time-honored experience in treating Tinea capitis. It is given orally and is ineffective topically. Hepatotoxicity is an occasional problem with prolonged use. Liver enzymes should be checked every 8 weeks during use.

5. (A) Fluconazole is also effective in preventing relapse of cryptococcal meningitis in patients with AIDS. C krusei is resistant to fluconazole.

6. (C) Patients may also have transient asymptomatic elevations of liver enzymes. Rashes have been reported, and rare reports of an exfoliative dermatitis in patients with AIDS receiving fluconazole have been described.

7. (E) Itraconazole is the preferred treatment for mild to moderate pulmonary disease caused by B dermatitidis. Fluconazole can be used as an alternative treatment for pulmonary blastomycosis (Table 100-1). For children who are immunocompromised or who have evidence of disseminated disease, amphotericin B is the treatment of choice.

8. (B) Itraconazole at high doses can cause hypokalemia and pedal edema. Life-threatening ventricular tachycardias can occur when the antihistamines terfenadine or astemizole are administered with itraconazole.

TABLE 100-1 Preferred Drugs for Initial Treatment of Serious Fungal Infections

 

DISEASE

PULMONARY, LIFE
THREATENING, 
OR DISSEMINATED

MILD TO
MODERATE
PULMONARY

 

Aspergillosis

Vor*

Itr

Blastomycosis

AmB

Itr

Candidiasis

AmB

Flu

Coccidioidomycosis

AmB

Itr or Flu

Cryptococcus

AmB

Flu

Histoplasmosis

AmB

Itr

Sporotrichosis

AmB

Itr

 

*Alternative therapy for invasive aspergillosis is AmB.
Flucytosine has been used in combination with AmB (particularly for meningitis).
Abbreviations: AmB, amphotericin B; Flu, fluconazole; Itr, itraconazole; Vor, voriconazole.

9. (B) Flucytosine can be used in combination with amphotericin B for meningeal or other serious cryptococcal infections as well as for C albicans infection involving the CNS. Drug levels in the CSF are up to 75% of those found in serum (Table 100-1).

10. (E) Voriconazole is a triazole derivative of fluconazole that exhibits a wide spectrum of activity against many important fungi including Candida, Aspergillus, Cryptococcus, and Fusarium. Voriconazole was superior to amphotericin B in a randomized study in adults. A new class of antifungal agents, the echinocandins, are recommended for the treatment of candidemia in adults with neutropenia, but this new class of drugs has not yet been approved by the FDA for treatment in children younger than 12 years (Table 100-1).

11. (B) For immunocompetent individuals with isolated symptomatic pulmonary infection, fluconazole is the drug of choice for pulmonary cryptococcosis.

12. (D) In the past, griseofulvin was the drug of choice for treatment of T unguium. Topical antifungal agents are ineffective because of the inability to penetrate the nail bed. Oral terbinafine is well absorbed and penetrates the nail bed. Oral terbinafine is now the treatment of choice for onychomycosis because it has been used successfully to treat T unguium in a much shorter period of time than previous antifungal medications.

13. (A) The duration of treatment recommended for onychomycosis of the fingernails is 6 weeks and 12 weeks for toenail onychomycosis.

14. (E) Permethrin 5% cream is a safe and effective therapy for scabies. The cure rate is greater than 90%. Side effects of permethrin 5% are minimal. In infants and young children the cream is applied to the entire head, neck, and body and then removed by bathing 8-14 hours later. Prophylaxis with permethrin 5% cream is also recommended for household members.

15. (A) The advantage of albendazole over mebendazole is its activity in a single oral dose of 400 mg for treatment of hookworm infection. Mebendazole (100 mg twice daily for 3 days) and pyrantel pamoate (11 mg/kg per day not to exceed 1 g/day for 3 days) are alternative treatments for hookworm infection.

16. (B) Either mebendazole or albendazole can be administered for the treatment of whipworm infection. Both should be given for a 3-day course. Albendazole (400 mg) and ivermectin (200 μg/kg) given together each in a single dose have been effective for treatment of whipworm infection.

17. (A) Metronidazole is an important drug as part of the treatment regimen for intra-abdominal anaerobic infections and brain abscess. It is also effective therapy for the treatment of intestinal or extraintestinal (such as liver abscess) disease caused by Entamoeba histolytica.

18. (B) Travelers to areas where chloroquine-resistant Plasmodium falciparum exists can take 1 of 3 regimens that include mefloquine hydrochloride, doxycycline, or atovaquone-proguanil. Chloroquine is still the drug of choice for malaria prophylaxis in areas in which P falciparum is still susceptible or nonfalciparum malaria (P vivaxP ovaleP malariae) only exist.


SUGGESTED READING

John CC. Drug treatment of malaria. Pediatr Infect Dis J. 2003;22:649-651.

Steinbach WJ, Dvorak CC. Antifungal agents. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008: 1452.

CASE 101: A 15-YEAR-OLD ADOLESCENT GIRL WITH FEVER, SHORTNESS OF BREATH, AND AN ABNORMAL CHEST RADIOGRAPH

A 15-year-old adolescent girl comes to your office on Friday morning with her 25-year-old sister. She indicates she has not been feeling well for 1-2 months. She remembers having a fever, sore throat, and rash about 2 months ago that resolved after 2 weeks. Her older sister tells you that the adolescent was seen at the emergency department for the acute illness. She recalls that blood was drawn and in a follow-up phone call later was told that the adolescent did not have infectious mononucleosis. Since then the adolescent has had fatigue and decreased appetite and thinks she may have lost some weight. She has also been too tired to try out for the high school basketball team. Her sister has also noticed a change in her younger sister’s activity level and insisted that she come to your office today because she was short of breath.

On physical examination the adolescent girl was alert and cooperative but appeared tired. Her temperature is 100.5°F (38.1°C). A fine white exudate is present on the buccal mucosa, posterior pharynx, and tongue. Posterior cervical and axillary adenopathy are noted. The respiratory rate is 30 per minute and scattered rales are heard at both the right and left lung bases. The heart and abdominal examinations are normal.

SELECT THE ONE BEST ANSWER

1. You are concerned about the possibility of an immunodeficiency disorder in this adolescent girl. The first laboratory test to order for the evaluation for immunodeficiency should be

(A) complete blood count (CBC) with differential

(B) quantitative immunoglobulin levels

(C) T-lymphocyte subsets

(D) total hemolytic complement activity

(E) HIV enzyme immunoassay

2. Human immunodeficiency virus infection is confirmed in this adolescent girl. In her case the most likely route of acquisition of HIV would likely be

(A) injecting drug use

(B) heterosexual contact with an HIV-infected person

(C) coagulation disorder

(D) perinatal exposure

(E) needlestick injury from an unknown source

3. The illness occurring in the adolescent girl 2 months before evaluation by her primary care pediatrician was acute HIV infection. The laboratory test to diagnose acute HIV infection is

(A) HIV EIA

(B) HIV Western blot

(C) HIV rapid test

(D) lymphocyte subsets

(E) HIV RNA PCR

4. A chest radiograph reveals bilateral alveolar disease with involvement of perihilar regions. The most likely diagnosis for the pulmonary abnormalities is

(A) CMV pneumonia

(B) pulmonary candidiasis

(C) Mycobacterium avium complex pneumonia

(D) Pneumocystis jiroveci pneumonia

(E) Legionella pneumophila pneumonia

5. The major risk factor for development of P jiroveci infection in HIV-infected individuals is

(A) suppression of cell-mediated immunity measured by the number of CD4+ lymphocytes in blood

(B) impaired specific antibody production after immunization with T-cell independent antigens

(C) depressed neutrophil superoxide production

(D) diminished capability of natural killer (NK) lymphocytes to mediate antibody-dependent cell-mediated cytotoxicity of HIV-infected cells

(E) complement deficiency involving the classical complement pathway

6. A 10-month-old male infant develops fever and shock, and a blood culture drawn before the start of antibiotic therapy grows Pseudomonas aeruginosa. The infant appears malnourished and has a weight less than 2 standard deviations below the mean for sex and age. The most likely underlying reason for the gram-negative septic shock is

(A) X-linked agammaglobulinemia

(B) immunodeficiency with hyperimmunoglobulinemia M

(C) protein-calorie malnutrition

(D) leukocyte adhesion deficiency type I

(E) common variable immunodeficiency

7. Protein calorie malnutrition can result in major immunodeficiency. The immune deficit associated with malnutrition is primarily

(A) T-cell cellular immunity

(B) B-cell humoral immunity

(C) neutrophil function

(D) complement system

(E) combined T-cell cellular and B-cell humoral immunity

8. A 4-year-old girl with a severe brain injury from IVH as a newborn does not develop fever in response to a documented infection with influenza virus. The most likely reason for this finding is

(A) damage to the thermoregulatory center in the hypothalamus

(B) inability to generate production of tumor necrosis factor-alpha

(C) inability to generate production of interleukin-1-beta

(D) deficiency of interferon-gamma in the systemic circulation

(E) deficiency of interleukin-2

9. A 3-year-old child presents to your office with fever of 103°F (39.4°C), cough, and rhinorrhea during the peak of an epidemic of influenza A. The child’s mother is very concerned about the fever. You counsel her regarding the fever that

(A) the high fever can increase the replication of influenza virus

(B) fever can enhance some immunologic responses such as movement and function of certain white blood cells

(C) fever is best treated with a cooling blanket

(D) antipyretic agents will shorten the duration and contagiousness of influenza

(E) high fever is less likely to occur in children compared with adults

10. A 12-month-old boy develops septic arthritis of the left knee with a positive blood and joint fluid culture for S pneumoniae. Protection against recurrent infection with this bacterial species correlates best with

(A) recruitment of T-helper cells (CD4+ cells)

(B) anti-C-polysaccharide antibody

(C) IgG 1 and IgG 3 subclass antibody

(D) maturation of the classical pathway of the complement system

(E) type-specific IgG anticapsular antibody

11. A 16-year-old previously healthy adolescent male presents with a 2-week history of fever associated with malaise, anorexia, and weight loss. He is diagnosed with pneumonia but when three blood cultures are reported positive for S aureus, an echocardiogram is performed. The results reveal tricuspid valve endocarditis. The major risk factor for development of endocarditis in this adolescent is

(A) unrecognized congenital heart disease

(B) prior rheumatic heart disease

(C) IV drug use

(D) immunodeficiency with an underlying phagocyte function disorder

(E) HIV infection

12. A 3-week-old female infant was born to a mother with a history of IV drug abuse. The mother had serologic testing for HIV, RPR, and HBsAg during the second trimester of pregnancy. All results were negative. The infant now presents at 3 weeks of age with a diffuse vesiculobullous rash that involves the palms and soles. The diagnostic test that will most likely reveal the etiology of the rash is

(A) culture of vesicle scrapings for HSV

(B) direct fluorescent antibody staining of vesicle scraping for varicella-zoster-virus

(C) RPR and FTA-ABS tests for syphilis

(D) Gram stain and bacterial culture of vesicle fluid

(E) urine culture for CMV

13. A 10-day-old term infant girl presents to your office with eyelid swelling, erythema, and mucopurulent drainage from the left eye. A culture of the conjunctiva does not grow N gonorrhoeae or other bacterial pathogens. What important historical factor in the mother will help best in determining the etiology of the newborn’s conjunctivitis?

(A) sexual history of the parents

(B) medication history

(C) surgical history

(D) history of prior miscarriages

(E) history of contact with other children in family with conjunctivitis

14. The mother of the 10-day-old infant with conjunctivitis should also have testing to determine possible infection with

(A) HSV

(B) toxoplasmosis

(C) hepatitis B virus

(D) CMV

(E) HIV

15. The indigenous bacterial flora of the gut are important in the pathogenesis of infection caused by pathogenic bacteria. Antimicrobial therapy can result in diarrhea with alterations in the colonic microflora. Antimicrobial therapy can lead to diarrhea with the overgrowth of which of the following bacteria?

(A) Campylobacter jejuni

(B) enterotoxigenic E coli

(C) Aeromonas hydrophila

(D) Clostridium difficile

(E) Yersinia enterocolitica

16. A 7-year-old boy with newly diagnosed AML has recently completed induction chemotherapy. He develops fever, neutropenia (absolute neutrophil count of 100 cells/mm3), and shock. All of the following bacteria are likely pathogens except

(A) S pyogenes

(B) S aureus

(C) S epidermidis

(D) P aeruginosa

(E) E coli

17. An 18-year-old girl with congenital asplenia associated with congenital heart disease develops fever to 104°F (40°C) associated with a faint maculopapular rash. The child is at high risk for fulminant infection with all of the following agents except

(A) H influenzae type b

(B) N meningitidis

(C) P aeruginosa

(D) S pneumoniae

(E) Salmonella typhimurium

18. A 4-year-old boy with ALL develops fever to 103°F (39.4°C). He also has neutropenia with an absolute neutrophil count of 200 cells/mm3. An appropriate antimicrobial regimen for initial empirical therapy is

(A) aztreonam

(B) ceftriaxone

(C) cefazolin and gentamicin

(D) trimethoprim-sulfamethoxazole and vancomycin

(E) ceftazidime

19. Aspergillus can cause invasive pulmonary infection in children with underlying medical problems. Of the following patients, the one most likely to develop invasive pulmonary aspergillosis is

(A) a 19-year-old adolescent boy with ALL in relapse with fever and neutropenia

(B) an 8-year-old girl with HIV infection and pneumonia and a CD4 percentage of 20%

(C) a 12-year-old girl with cystic fibrosis, new infiltrates on chest radiographs, and hypoxia

(D) a 4-year-old boy with common variable immunodeficiency who develops pneumonia

(E) a 5-year-old girl with terminal complement component deficiency

ANSWERS

1. (A) Obtaining a CBC, differential, and platelet count provides a great deal of information; the results give information regarding leukocytosis, leukopenia (lymphopenia, neutropenia), leukocyte morphology, the presence of Howell-Jolly bodies, anemia, and thrombocytopenia.

2. (B) Among adolescents in the 13-19-year age group, the proportion of cases of HIV/AIDS in girls in 2007 was about a third that in boys (Table 101-1). The major route of transmission in adolescent girls is heterosexual transmission. Most HIV-infected adolescents are asymptomatic and not aware they are infected. In 2007 among adolescents 13-19 years of age diagnosed with AIDS, 40% were female.

3. (E) Acute HIV infection should be considered in any adolescent with a mononucleosis-like illness. Fever, fatigue, pharyngitis, lymphadenopathy, mucocutaneous ulcers, and rash are common signs and symptoms seen with acute HIV infection. Initial HIV antibody tests are often negative, which emphasizes the importance of using nucleic acid amplification tests that can detect HIV-1 RNA for diagnosis.

TABLE 101-1 Distribution of Cases of HIV/AIDS Cases Reported Among Adolescents and Young Adults by Sex and Age Groups*

 
 

AGE IN YEARS

SEX

13-19

20-24

≥25

 

Female

31%

23%

26%

Male

69%

77%

74%

 

*From 34 states with confidential name-based HIV infection reporting in 2007.
Data from U.S. Centers for Disease Control and Prevention.

4. (D) P jiroveci most commonly occurs in HIVinfected children 3-6 months of age. Nevertheless, in adolescents Pneumocystis pneumonia is still a more common AIDS-defining diagnosis than Candida, CMV, or M avium complex (MAC) disease.

5. (A) Epidemics of PCP have occurred in malnourished infants and children, as well as premature infants. With HIV infection, the risk of PCP is related to the viral-induced suppression of cellmediated immunity. The decision to administer PCP prophylaxis is based on the total CD4 lymphocyte count and percentage.

6. (C) Protein calorie malnutrition is a condition that can predispose to recurrent infections. Cellular immunity is important for protection against enteric bacteria.

7. (A) With malnutrition associated with protein/energy deficiency, there are immune deficits involving cellular immunity and T-cell function. IgA and E levels may be decreased.

8. (A) The pathogenesis of fever involves cytokinestimulation of the preoptic area of the hypothalamus (thermoregulatory center), which leads to the production of prostaglandin E2. This molecule is thought to activate thermoregulatory neurons to raise the thermostat set point. Then peripheral mechanisms are activated that lead to vasoconstriction and muscle contraction, which result in the generation of fever. Also certain areas in the cerebral cortex are stimulated to promote behavioral changes designed to help control temperature.

9. (B) There is evidence that fever is more beneficial than harmful to the host. High temperature interferes with the replication and virulence of certain pathogens. Fever represents a regulatory mechanism to reduce cytokine activation in the acute inflammatory response. Controversy exists about whether febrile episodes should be treated. A short course of an antipyretic drug has low risk for toxicity, and most of the appropriate antipyretic drugs also have analgesic properties.

10. (E) Immunity to S pneumoniae is related to the production of type-specific humoral immunity. Development of type-specific antibodies against the capsular polysaccharide correlates with immunity to that specific serotype. Children with deficiency of the classical pathway of complement such as C2 deficiency are at increased risk for invasive infections caused by S pneumoniae. IgG subclass deficiencies are not associated with an increased risk for invasive pneumococcal infections.

11. (C) In this previously healthy adolescent, IV drug use would be the most likely risk factor for development of right-sided endocarditis. Other risk factors for right-sided endocarditis include the presence of pacemakers, wires, and long-term central venous catheterization.

12. (C) The description of the rash is most characteristic of congenital syphilis, even though the RPR drawn on the mother in the second trimester was nonreactive. A history of IV drug use should raise the suspicion of syphilis as well as HIV and hepatitis B infection. Another important risk factor for vertical transmission of syphilis is lack of prenatal care.

13. (A) The most likely pathogen in this case of mucopurulent conjunctivitis is C trachomatis, a sexually transmitted disease (STD). Many men and women infected with C trachomatis are either asymptomatic or mildly symptomatic so a history of sexual activity is important to obtain. Symptoms of conjunctivitis in the newborn infant due to C trachomatis usually present within 5-14 days after birth but can be seen as late as 60 days.

14. (E) In this clinical setting, the infant most likely has infection with C trachomatis. Individuals who have an STD such as C trachomatis or N gonorrhoeae should also be evaluated for HIV infection.

15. (D) Diarrhea can occur during therapy with many different antimicrobial agents. Antimicrobialassociated diarrhea can result from either changes in small bowel peristalsis or from alteration in the normal flora found in the intestine. A good example of the latter is overgrowth in the colon of C difficile.

16. (C) Patients with fever and neutropenia can develop infections caused by coagulase-negative staphylococci such as S epidermidis. However, this is a more indolent infection, and a short delay in administration of specific antimicrobial therapy has not been shown to be detrimental to the patient’s outcome. The other bacteria listed can all cause fulminant infection resulting in death.

17. (C) Patients with asplenia are at increased risk for overwhelming life-threatening infections. The most common organism involved is S pneumoniae, but other encapsulated bacteria can cause fulminant infections. Fulminant septicemia has also been reported in asplenic patients caused by Capnocytophaga canimorsus. This species is part of the normal mouth flora of dogs.

18. (E) A number of studies have shown no differences between monotherapy and multiple drug therapy for empirical treatment of uncomplicated episodes of fever in neutropenic patients. A third- or fourthgeneration cephalosporin (ceftazidime or cefepime) or a carbapenem (imipenem-cilastin or meropenem) may also be used. The other antibiotic regimens listed above except gentamicin do not have appreciable activity against P aeruginosa.

19. (A) In children, the most common presentation of invasive pulmonary aspergillosis occurs in the setting of fever and neutropenia without any initial respiratory tract symptoms, and there is a failure to respond to broad-spectrum antibacterial therapy. Bacterial pathogens, especially S pneumoniae and H influenzae, most commonly are the etiologic agents of pneumonia in patients with common variable immunodeficiency.


SUGGESTED READING

Aggarwal M, Rein J. Acute human immunodeficiency virus syndrome in an adolescent. Pediatrics. 2003:112: e323.

Goldman AS. Back to basics: host responses to infection. Pediatr Rev. 2000;21:342-349.

Shetty AK, Maldanado YA. Epidemiology and prevention of HIV infection in children and adolescents. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008:641.

CASE 102: A 2-WEEK-OLD WITH FEVER, RASH, AND A SEIZURE

A 3000-g infant was born at 40 weeks’ gestation to a 24-year-old G1P1 white woman by normal spontaneous vaginal delivery. The infant was discharged in 2 days, and mother was breast-feeding the infant without difficulty. An office visit in the first week of life revealed that the infant was afebrile, breast-feeding well, and back to birthweight.

At 2 weeks of age the mother noticed that the infant was not breast-feeding as well. This continued for 24 hours when the mother measured the infant’s temperature at 101.1°F (38.4°C). The mother called you, and you advised her to bring the infant directly to the pediatric emergency department.

On physical examination at the emergency department, the infant is found to be sleepy but arousable. The temperature is 100.7°F (38.2°C). The infant has two papulovesicular lesions on the right arm. The oropharynx and eye examination are normal. Examination of the lungs and heart also are normal. There are no focal neurologic deficits.

SELECT THE ONE BEST ANSWER

1. The most accurate statement regarding neonatal HSV with disease localized to the skin, eyes, and mouth (SEM) is

(A) if untreated, 20% of neonates progress to disseminated or CNS disease

(B) most neonates infected with HSV in the perinatal period are born to women who are completely asymptomatic for genital HSV infection during pregnancy and at delivery

(C) women who have recurrent HSV genital infection cannot transmit the virus by an ascending infection from the genital tract

(D) treatment of a neonate with an SEM presentation includes acyclovir at a dose of 10 mg/kg every 8 hours IV for 10 days

(E) the recommended duration of treatment for HSV SEM disease is the same as for CNS disease

2. The risk of HSV infection in a neonate varies based on the type of HSV infection in the mother. The risk of neonatal infection in primary versus recurrent HSV infection in the mother is

(A) 50% versus 8%

(B) 50% versus 10%

(C) 25% versus 2%

(D) 25% versus 20%

(E) 25% versus 10%

3. You suspect congenital CMV infection in a term newborn infant with bilateral sensorineural hearing loss. Vertical transmission of CMV to an infant occurs by all except one of the following methods

(A) transplacental passage of blood-borne virus

(B) at delivery by exposure to virus in the maternal genital tract after maternal primary infection

(C) at delivery by exposure to virus in the maternal genital tract after reactivation of infection during pregnancy

(D) by ingestion of breast milk in the postnatal period

(E) asymptomatic oral shedding of CMV in postnatal period

4. In healthy children and adolescents, infectious mononucleosis is a self-limited disease. However, some children can develop serious complications from EBV. The most likely disorder associated with complicated EBV infection is

(A) primary immunodeficiency involving T lymphocytes

(B) primary immunodeficiency involving B lymphocytes

(C) primary immunodeficiency involving phagocytes

(D) primary immunodeficiency involving complement

(E) secondary immunodeficiency involving B lymphocytes

5. A 5-year-old boy with ALL develops fever of 102.2°F (39°C) and a vesicular rash involving the face, trunk, extremities, palms, and soles. Some of the vesicular lesions are deep-seated with surrounding erythema. You suspect hemorrhagic varicella, which is confirmed by DFA staining of the skin lesions. The most common life-threatening complication of varicella in immunocompromised children is

(A) encephalitis

(B) hepatitis

(C) pneumonia

(D) necrotizing fasciitis

(E) secondary bacterial infection with group A streptococcus

6. An 8-month-old male infant who recently came to the United States with his family from Mexico presents to your office with a 4-day history of fever associated cough, coryza, and conjunctivitis. On the third day of illness, a maculopapular rash began along the hairline and spread to involve the face, neck, trunk, and extremities. You strongly suspect the diagnosis of measles. The complication that causes the most morbidity in young children with this disease is

(A) encephalitis

(B) hemorrhagic shock

(C) pneumonia

(D) myocarditis

(E) hepatitis

7. An 8-year-old girl develops fever of 102°F (38.8°C), bilateral swelling of the parotid glands, and headache. You suspect mumps. The most likely complication of mumps is

(A) pancreatitis

(B) meningitis

(C) sensorineural hearing loss

(D) myocarditis

(E) glomerulonephritis

8. A 17-year-old adolescent female in her junior year of high school develops a low-grade fever of 101°F (38.3°C), a maculopapular rash that first appears on the face, and suboccipital/postauricular lymphadenopathy. You suspect rubella and confirm the diagnosis by serology. Serologic surveys of young adults indicating the percentage that are susceptible to rubella are

(A) 3%

(B) 5%

(C) 10%

(D) 15%

(E) 25%

9. A 4-year-old boy with sickle cell disease (homozygous hemoglobin SS disease) develops mild fever of 100.5°F (38°C) associated with fatigue for 2 days. On physical examination he is noted to have pallor. Laboratory results reveal a WBC count of 6800/mm3, hemoglobin 5.4 g/dL; the reticulocyte count is 0.7%; and the platelet count is 150,000/mm3. The most likely etiology of the severe anemia in this child is

(A) parvovirus B19

(B) human herpes virus type VI

(C) human herpes virus type VIII

(D) coxsackie virus A16

(E) adenovirus

10. A 13-month-old infant boy has mild nasal congestion and eyelid edema associated with erythema of the palpebral conjunctiva for 1 day. He then develops fever of 104°F (30°C) associated on the same day with a 5- to 10-minute generalized tonic-clonic seizure. The child’s parents bring him to the emergency department. After an observation period, the temperature decreased to 101°F (38.3°C) and he is alert and consolable. The most likely etiology of the seizure is

(A) adenovirus

(B) RSV

(C) influenza A

(D) Shigella sonnei (E) HHV-6

11. A 15-month-old boy is evaluated for recurrent bacterial infections (one episode of culture-proven pneumonia caused by S pneumoniae and one episode of septic arthritis caused by S aureus). On physical examination the infant is afebrile; the weight is at the 5th percentile for age, and he has hepatosplenomegaly and generalized lymphadenopathy. The most likely etiology to explain these findings is

(A) Epstein-Barr virus

(B) HIV

(C) CMV

(D) Histoplasma capsulatum infection

(E) adenovirus

12. Enteroviruses often cause a nonspecific febrile illness in young children but can also cause exanthems. All of the following exanthems have been reported to be caused by the nonpolio enteroviruses except

(A) papular-purpuric rash in a glove-and-stocking distribution

(B) papulovesicular rash

(C) papular urticaria

(D) petechial rash

(E) maculopapular rash

13. In January you are seeing large numbers of children in your office with fever and respiratory symptoms. You suspect influenza as the likely etiology. Compared with children younger than 5 years old, children older than 5 years of age are more likely to have

(A) flulike syndrome of fever, cough, headache, myalgia, malaise

(B) laryngotracheobronchitis

(C) an illness requiring hospitalization

(D) vomiting, diarrhea, abdominal pain

(E) bronchiolitis

14. A 12-month-old boy develops fever, cough, rhinorrhea for 2 days followed by the onset of inspiratory stridor. The month is October, and you suspect laryngotracheobronchitis (croup) caused by parainfluenza virus. A true statement about the epidemiology of parainfluenza virus is

(A) parainfluenza virus type IV causes epidemics of croup in the summer every year

(B) parainfluenza virus type III causes epidemics of croup in the spring of odd-numbered years

(C) parainfluenza virus type II causes epidemics of croup in the fall of even-numbered years

(D) parainfluenza virus type I causes epidemics of croup in the fall of odd-numbered years

(E) parainfluenza virus type III causes epidemics of croup in the winter of every year

15. During July a 6-year-old girl develops fever of 103°F (39.4°C) that persists for 5 days. Associated symptoms include sore throat. On physical examination the child has follicular injection of the tonsillar pillars, bilateral purulent conjunctivitis, cervical lymphadenopathy, and preauricular lymphadenopathy. The most likely etiologic agent is

(A) enterovirus

(B) C trachomatis

(C) influenza

(D) H influenzae

(E) adenovirus

16. A 4-month-old male infant is hospitalized in January with fever, cough, rhinorrhea, and bilateral wheezing associated with respiratory distress. RSV infection is confirmed by EIA performed on nasal secretions. All of the following strategies are important for reducing the risk of nosocomial transmission of RSV except

(A) handwashing

(B) use of gowns, gloves, and goggles

(C) contact precautions for infected patients

(D) droplet precautions for infected patients

(E) cohorting of infected patients

17. A 10-month-old unimmunized infant girl is seen at the emergency department in February with a 2-day history of fever of 103°F (39.4°C) associated with vomiting. The infant is admitted to the hospital with dehydration. After admission, she passes a large watery stool. The best diagnostic study to perform on the stool is

(A) antigen testing for rotavirus

(B) culture for Campylobacter jejuni (C) antigen testing for norovirus

(D) enzyme immunoassay for C difficile toxin

(E) culture for enteric adenovirus

18. A 12-year-old boy comes to your office with sudden onset of vomiting associated with fever of 101°F (38.3°C) and myalgias, headache, and chills. The patient is not dehydrated, and you recommend symptomatic treatment. The next day you learn from the school nurse that more than half of the patient’s classmates have similar symptoms and some also have diarrhea. The most likely etiology of your patient’s illness is

(A) astrovirus

(B) calicivirus

(C) hepatitis E

(D) pestivirus

(E) coronavirus

ANSWERS

1. (B) When an SEM presentation in a neonate is not promptly treated, 75% of cases progress to disseminated or CNS disease. Both primary and recurrent infections frequently are asymptomatic. The treatment of neonatal HSV infection includes acyclovir at a dose of 20 mg/kg every 8 hours IV for 14-21 days.

2. (C) The risk of transmission to an infant born to a mother who has recurrent HSV infection is significantly less than from a mother who has primary infection (2% versus 25-60%). This difference is thought to be largely related to the HSV antibody status of the mother.

3. (E) Approximately 10% of mothers seropositive for CMV shed the virus during delivery, and about 50% of infants exposed to the virus during birth are infected. Oral shedding is common in young children with rates as high as 70% in 1- to 3-year-old children in child-care centers. Spread of CMV in households and child-care centers is well documented, but oral shedding is not a method by which congenital CMV infections are thought to occur.

4. (A) EBV infection is controlled through the production of CD8 + cytotoxic T-lymphocytes, which limit primary infection and keep the pool of EBVinfected B lymphocytes in check. NK cells also play a role in the lysis of EBV-infected lymphocytes. Examples of impairment of cell-mediated immunity that result in suboptimally contained EBV infection include lymphoma, X-linked lymphoproliferative syndrome, and posttransplant lymphoproliferative disorder.

5. (C) Hemorrhage into cutaneous lesions is also a sign of severe varicella in a pediatric patient who is immunocompromised. In contrast to the vesicles of varicella seen in healthy children, the vesicles in children who are immunocompromised are larger and often umbilicated. The lesions are widely distributed and also can occur on the palms and soles. Although several of the choices represent serious complications of varicella, pneumonia is universally present among those with fatal varicella.

6. (C) Pneumonia is the most serious complication associated with measles, accounting for approximately 60% of the deaths in infants who have measles. The respiratory clinical manifestations of measles include bronchopneumonia, bronchiolitis, laryngotracheobronchitis, and lobar pneumonia. Mortality among children in the United States was 1-3 per 1000 with measles. Encephalitis occurs in 1 in 1000 cases of measles and is more common in older children and adolescents. Measles has not been endemic in the United States since 1997. Limited cases of measles have continued to occur that are imported.

7. (B) Although more than 50% of individuals with mumps parotitis (see Figure 102-1) have CSF pleocytosis, only 1-10% have symptoms of CNS infection. Aseptic meningitis is the most frequent CNS infection. Myocarditis is a rare complication of mumps. Orchitis can also be a complication that occurs in up to 35% of boys with mumps. This complication is uncommon in prepubertal males and is usually unilateral.

art

FIGURE 102-1. Mumps parotitis. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention.)


8. (C) Rubella is a mild disease characterized by a generalized erythematous maculopapular rash, generalized lymphadenopathy, and low-grade fever. The risk of acquiring rubella is low in all age groups. However, in the vaccine era, most cases occurred in young unimmunized adults in outbreaks on college campuses and in occupational settings. In March 2005, the CDC declared that rubella is no longer endemic in the United States.

9. (A) Parvovirus B19 (see Figure 102-2) can cause a transient aplastic crisis that can be severe in individuals with hemolytic disorders, hemoglobinopathies, red cell enzyme deficiencies, and autoimmune hemolytic anemias. Life-threatening anemia is common when aplastic crises develop, particularly in children who have homozygous (SS) sickle cell disease.

art

FIGURE 102-2. Parvovirus B-19. Erythema infectiosum. (Reproduced, with permission, from Lichtman MA, Beutler E, Kipps TJ, et al. Williams Hematology, 7th ed. New York: McGraw-Hill; 2006: Plate XXV-19.)


10. E) CNS manifestations are common in infants with HHV-6 infection, with seizures the most common CNS manifestation. Seizures occur during the febrile period in 10-15% of children with primary infection. The risk of seizures is greatest for children who develop primary HHV-6 infection during the second year of life.

11. (B) Children with HIV infection may present with multiple or recurrent serious bacterial infections. Combined with hepatosplenomegaly, lymphadenopathy, and failure to thrive, HIV is the most likely diagnosis to consider. EBV, CMV, and Histoplasma capsulatum can cause hepatosplenomegaly and failure to thrive but are not associated with recurrent, serious bacterial infections.

12. (A) The type of rashes associated with enterovirus infections include maculopapular, petechial, urticarial, and vesicular. The papular-purpuric glove-and-stocking distribution syndrome is classically caused by parvovirus B19.

13. (A) Unimmunized older children and adults with influenza are more likely to have an abrupt onset of illness associated with fever and chills, headaches, sore throat, myalgia, and a dry cough. The rate of hospitalization in unimmunized children younger than 2 years is comparable with the rates of hospitalization among the elderly with underlying medical conditions.

14. (D) Since 1971, when surveillance for croup began in the United States, parainfluenza virus type I has caused epidemics of croup in the fall of oddnumbered years. Compared with the other parainfluenza viruses, infection with type III occurs more often in infants. Parainfluenza virus type III is second in frequency to RSV as a cause of bronchiolitis.

15. (E) The child likely has pharyngoconjunctival fever. Outbreaks of pharyngoconjunctival fever have occurred at swimming pools and summer camps. The most common site of involvement of adenovirus is the upper respiratory tract. Infants and young children often develop upper respiratory illness with serotypes 1-3, 5, and 7. Adenovirus infections occur year round but can produce sporadic infections, most commonly in the winter, spring, and early summer.

16. (D) Nosocomial transmission of RSV in the hospital setting is an annual problem, but studies have indicated there are strategies that can be employed to decrease the risk of transmission. The major source of spread of RSV is by direct contact. Outbreaks of RSV occur in temperate climates every year during winter and early spring. Most hospitalizations for RSV occur in 2- to 6-month-old children. Besides the most recognized clinical manifestations of bronchiolitis, RSV can also cause pneumonia, upper respiratory tract infection, croup, apnea, and otitis media.

17. (A) This young child most likely has rotavirus infection. Rotavirus has an annual peak of infection and illness in the winter. Children usually experience their first rotavirus infection between 3 and 24 months of age. Infections during the first 3 months of life and reinfections among older children are more likely to be asymptomatic. Rotavirus causes gastroenteritis and is more likely to cause dehydration than other viral agents that cause gastroenteritis. Vomiting and fever may precede the diarrhea in children, ultimately requiring hospitalization.

TABLE 102-1 Factors Contributing to Caliciviruses as Causes of Outbreaks

 

FACTOR

OBSERVATION

 

Low infectious dose

Less than 102 viral particles

Asymptomatic shedding

Up to 2 wk

Stable in environment

Survives freezing, heating up to 60C, and 10 ppm chlorine

Strain diversity

Multiple genotypes

Immunity

Antibody not correlated with long-term protection

Multiple means of transmission

Fecal-oral, large droplets, environmental contamination

Data from Bresee JS, Widdowson M, Monroe SS, et al. Foodborne viral gastroenteritis: challenges and opportunities. Clin Infect Dis. 2002;35:748.

18. (B) Caliciviruses have caused outbreaks of gastroenteritis in all age groups and are associated most commonly with contamination of seafood and water. A number of characteristics of caliciviruses facilitate their causing outbreaks of gastroenteritis (Table 102-1). Outbreaks have occurred on cruise ships, child-care centers, and nursing homes. Caliciviruses can also cause sporadic gastroenteritis in children and adults in community settings. Commercial assays to detect caliciviruses are not available, but a RT-PCR assay has been used to detect viral RNA in the stool. This assay is useful for identifying caliciviruses as the cause of an outbreak of gastroenteritis and may be available through local and state departments of public health.


SUGGESTED READING

Kimberlin DW. Herpes simplex infections of the newborn. Semin Perinatol. 2007;31:19-25.

Pickering LK, Baker CJ, Kimberlin DW, Long SS. Red Book2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

CASE 103: A 15-MONTH-OLD WITH FEVER AND TACHYPNEA

A 15-month-old male infant has a 7-day history of cough and rhinorrhea. He had one previous episode of wheezing at age 4 months. His mother is concerned that he may be having difficulty breathing and is wheezing. There is also a strong family history of asthma on the paternal side. He is now brought to your office because of fever and some difficulty breathing. An older brother and uncle who live with the family have been ill with cough and sore throat. The child has received 3 H influenzae type b conjugate and three pneumococcal conjugate vaccines according to records.

On physical examination the child is sitting quietly in his mother’s arms. The temperature is 102°F (38.9°C). There is nasal flaring along with clear rhinorrhea. The respiratory rate is 48 per minute, and breath sounds are decreased when auscultating at the right posterior chest. There is no hepatosplenomegaly. A pulse oximeter is available in your office. In room air the infant’s oxygen saturation is found to be 92%.

SELECT THE ONE BEST ANSWER

1. You order a chest radiograph that reveals right middle and right lower lobe infiltrates and a large pleural effusion. A thoracentesis is performed after the child is admitted to the hospital; purulent fluid with a leukocyte count of 55,000/mmis obtained. The most likely etiology of the pneumonia and empyema is

(A) S aureus

(B) Streptococcus pyogenes

(C) Klebsiella pneumoniae

(D) H influenzae type b

(E) Neisseria meningitidis

2. A 4-month-old infant girl develops fever of 102°F (38.8°C) with acute swelling of the left anterior neck. An abscess in the anterior cervical triangle lymph node is drained and the culture grows MRSA. The isolate is susceptible to vancomycin, clindamycin, trimethoprim-sulfamethoxazole, and rifampin but resistant to erythromycin. The D-test is negative. Among the following, the antibiotic of choice for this infection is

(A) clindamycin

(B) rifampin

(C) azithromycin

(D) cefazolin

(E) meropenem

3. A previously healthy 4-month-old infant boy presents with a history of decreased bowel movements, poor feeding, and decreased activity. On physical examination the temperature is 100°F (37.8°C). The infant is alert, the pupils are sluggishly reactive, and he exhibits poor head control and hypotonia. The most likely etiology to explain these findings is

(A) hypothyroidism

(B) congenital myasthenia gravis

(C) infant botulism

(D) Guillain-Barré syndrome

(E) congenital myopathy

4. An 18-month-old girl develops a minor scalp wound and is well until 2 weeks later when she develops trismus and severe generalized muscular spasms. Her mother tells you her daughter has received no immunizations. You suspect tetanus caused by Clostridium tetani. Initial treatment considerations should include all of the following except

(A) IV metronidazole

(B) IV penicillin

(C) tetanus toxoid-containing vaccine

(D) diazepam to control muscle spasms

(E) TIG

5. A pregnant woman at 33 weeks’ gestation develops fever, headache, diarrhea, and back pain. Labor ensues and a 2-kg premature infant girl is born with respiratory distress, apnea, and shock. Pneumonia is identified by a chest radiograph. You obtain the history from the father that about 2 weeks before delivery, the mother ate some soft Mexican cheese. The infection suggested by the clinical scenario is

(A) Pseudomonas aeruginosa

(B) Listeria monocytogenes

(C) S pyogenes

(D) S aureus

(E) S pneumoniae

6. A 5-month-old infant boy with a 2-day history of rhinorrhea develops a persistent cough and an episode of apnea. Bordetella pertussis infection is confirmed by culture. The reservoir for B pertussis in this case most likely is

(A) 4-year-old sibling with cough and conjunctivitis

(B) 6-month-old cousin with rhinorrhea

(C) 13-year-old sibling with post-tussive emesis

(D) 65-year-old grandfather with a productive cough

(E) 12-month-old infant from the same child-care facility with a 3-day history of cough and rhinorrhea

7. An 8-month-old infant girl who has received three doses of H influenzae type b conjugate vaccine develops fever, irritability, and vomiting. A Gram stain of CSF reveals small gram-negative coccobacilli. The most likely etiology of the meningitis is

(A) H influenzae type b

(B) H influenzae type f

(C) E coli

(D) Salmonella choleraesuis

(E) Brucella melitensis

8. A 2-year-old boy living in the southeastern United States who attends day care has acute otitis media. You suspect infection with penicillin nonsusceptible S pneumoniae. The drug of choice for treatment of this infection is

(A) amoxicillin 80 mg/kg per day

(B) amoxicillin-clavulanate 80 mg/kg per day, amoxicillin component

(C) clindamycin 30 mg/kg per day

(D) azithromycin 10 mg/kg per day

(E) cefdinir 14 mg/kg per day

9. A 12-month-old girl develops fever and a maculopapular rash that becomes petechial 6 hours later. The child has a CSF pleocytosis, and both blood and CSF cultures grow N meningitidis serogroup C. She initially receives a single dose of ceftriaxone followed by IV penicillin G. All of the following contacts should receive chemoprophylaxis except

(A) 3-year-old sister

(B) 2-year-old nursery school contact

(C) pediatric resident who performed the spinal tap

(D) 13-year-old cousin visiting from out of state for the past week

(E) the child’s 23-year-old mother

10. An 8-year-old girl develops fever, and a blood culture yields Staphylococcus epidermidis. In which setting is this positive blood culture most likely to represent a contaminant?

(A) a 4-year-old child with leukemia who develops fever and neutropenia

(B) a 20-year-old with an audible murmur diagnosed as mitral valve prolapse

(C) a 2-year-old child with a ventriculoperitoneal shunt secondary to hydrocephalus

(D) a 3-year-old child with a central venous catheter who is receiving total parenteral nutrition because of short bowel syndrome

(E) a 28-week premature neonate receiving total parenteral nutrition

11. An 8-year-old girl has a fever of 103°F (39.4°C) for 2 days with cough, rhinorrhea, sore throat, and dyspnea. A chest radiograph reveals a small right lower lobe infiltrate. Antibiotic therapy with azithromycin is initiated, but 24 hours later, the child is evaluated at the emergency department. Findings on physical examination reveal an ill-appearing child, temperature: 104°F (40°C), respiratory rate 30/minute, blood pressure 60/25 mm Hg, hyperemic tonsils and posterior pharynx, and a generalized, erythematous, macular rash. A throat culture is obtained that reveals the colonies depicted in Figure 103-1. The most likely diagnosis is

(A) Stevens-Johnson syndrome

(B) Kawasaki disease

(C) Rocky Mountain spotted fever

(D) human monocytic ehrlichiosis

(E) streptococcal toxic shock syndrome

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FIGURE 103-1. Blood agar plate that reveals characteristic beta-hemolytic colonies characteristic of S pyogenes. Note the areas of enhanced beta-hemolysis where the agar was stabbed after the throat culture swab was plated.


12. A pregnant woman is screened for rectal and vaginal colonization with group B streptococcus (GBS) at 35 weeks’ gestation. All of the following are indications for intrapartum prophylaxis to prevent early-onset GBS disease except

(A) GBS bacteriuria during current pregnancy

(B) delivery at 36 weeks’ gestation with unknown GBS status

(C) rupture of membranes for 18 hours during labor with unknown GBS status

(D) previous pregnancy with a positive GBS screening culture

(E) previous birth of infant with invasive GBS disease

13. A 4-year-old girl has a high fever, and a blood culture is positive for E faecalis. In which clinical setting is enterococcal bacteremia most likely to occur with this young girl?

(A) child hospitalized in the pediatric intensive care unit with a central venous catheter

(B) child with first episode of a urinary tract infection

(C) child with a seizure and a lumbar puncture revealing CSF pleocytosis

(D) child with an isolated ventricular septal defect

(E) newborn infant born to a mother with chorioamnionitis

14. A 15-year-old adolescent girl develops pain in the hands and wrists 4 days after the start of her menstrual period. She then develops scattered papules on both hands while the pain in the hands and wrists improves. She then develops swelling of her left knee, which prompts medical attention. You suspect disseminated gonococcal infection. The most reliable method to diagnose this infection is by

(A) culture of blood

(B) PCR of blood

(C) culture of joint fluid

(D) gram stain smear of pharyngeal secretions

(E) culture or rRNA probe of endocervical secretions

15. A 3-year-old boy is bitten on his right lower leg by a dog in the neighborhood. Twelve hours later he develops fever to 102°F (38.8°C) and chills. The bite wound has swelling, erythema, tenderness, and a serosanguineous drainage. The most likely etiology of this wound infection is

(A) Eikenella corrodens

(B) Pasteurella multocida

(C) P aeruginosa

(D) S pyogenes

(E) Salmonella serotype Marina

16. A 4-year-old girl develops fever, vomiting, and hematochezia. A stool culture grows Salmonella enteritidis. The child recovers from the illness, but a stool culture sent 12 weeks later is still positive for S enteritidis. The organism is susceptible to ampicillin, ceftriaxone, trimethoprim-sulfamethoxazole, and gentamicin. At this point appropriate treatment would include

(A) trimethoprim-sulfamethoxazole

(B) gentamicin

(C) high-dose amoxicillin combined with probenecid

(D) no antimicrobial therapy

(E) cefixime

17. A 3-year-old girl develops fever, abdominal cramps, and mucoid bloody stools. A stool culture grows S sonnei, and the child is treated with trimethoprimsulfamethoxazole based on susceptibility testing. Two days after the onset of the girl’s symptoms, her 2-year-old brother also develops fever, vomiting, and profuse watery diarrhea. A stool culture is negative. Appropriate management of this sibling includes

(A) antimicrobial therapy with trimethoprimsulfamethoxazole

(B) diagnostic assay of stool for rotavirus antigen

(C) C difficile toxin assay on stool

(D) CBC with differential

(E) repeat stool culture for S sonnei

18. In December, a 6-month-old male infant develops fever, vomiting, and diarrhea that contains mucus and blood. He is bottle-fed infant formula. A stool culture sent grows Yersinia enterocolitica. The most likely source of the Y enterocolitica in this case is

(A) contaminated well water

(B) pork intestines (chitterlings)

(C) pasteurized milk

(D) raspberry-flavored baby food

(E) contaminated apple juice

ANSWERS

1. (A) Although all of the bacterial pathogens listed can cause pneumonia with empyema, S aureus is the most common cause among these pathogens. S pneumoniae is another major cause, but the child has been immunized. Use of the pneumococcal conjugate vaccine has resulted in a decrease in the incidence of invasive pneumococcal disease, including pneumonia/empyema.

2. (A) Clindamycin would be the most appropriate antibiotic in this case of community-associated MRSA infection after surgical drainage. There has been an increase in soft tissue infections as well as more serious invasive infections because of MRSA in most areas of the United States. Vancomycin should be reserved for more critically ill patients.

3. (C) Botulism is caused by Clostridium botulinum, a gram-positive anaerobic bacillus found in soil and agricultural products. Ingestion of honey is a risk factor for infant botulism, but in most infants, no source of the C botulinum spores can be found. Decreased frequency of bowel movements is a common symptom as are the other clinical features listed. The diagnosis can be confirmed by culture of the organism or identification of C botulinum toxin in the stool. The mainstay of management of infants with botulism is supportive care. Human botulism immune globulin intravenous (BIG-IV) is available for treatment.

4. (C) The initial goals of treatment of tetanus include neutralization of toxin, eradication of C tetani, and supportive care. Antimicrobial therapy to eradicate the organism can include metronidazole, penicillin, or tetracycline. IVIG can be considered for treatment if TIG is not available. Tetanus toxoid will not provide antibody quickly enough to be helpful.

5. (B) Listeria monocytogenes can manifest a similar clinical picture to that caused by Streptococcus agalactiae (group B streptococcus) with early-onset sepsis or late-onset meningitis. Prematurity, pneumonia, and septicemia are common in early-onset disease. Perinatal infection can result in stillbirth or neonatal death in approximately 20% of infections in pregnancy.

6. (C) There was been an increase in reported cases from 1997 to 2009 of pertussis in adolescents and adults. Up to a third of adolescents and adults with prolonged cough illness were shown to have pertussis. Neonates with pertussis are likely to have been born to young mothers with an illness characterized by cough. These findings support the current concept that older individuals are the major reservoirs of B pertussis. Conjunctivitis is not a feature of pertussis, but post-tussive emesis is. Nearly 17,000 cases were reported in 2009.

7. (B) The Gram stain that reveals gram-negative coccobacilli is consistent with H influenzae. The incidence of H influenzae type b meningitis has declined dramatically since routine immunization of young infants against H influenzae type b began. Invasive disease by non–type b encapsulated strains and nontypeable strains still does occur, and in most states, the incidence of invasive disease due to non–type b strains is higher than with type b strains. A recent vaccine shortage was announced with a small uptick of serotype b illness that was rare among fully immunized children.

8. (A) Amoxicillin is the drug of choice for treatment of acute otitis media, including infection caused by penicillin-nonsusceptible S pneumoniae. With use of this dose of amoxicillin, the concentration of the antibiotic in middle ear fluid is believed to be high enough to eradicate penicillin nonsusceptible strains of S pneumoniae. The addition of clavulanate unnecessarily broadens the antimicrobial spectrum.

9. (C) Chemoprophylaxis to prevent invasive meningococcal disease for health-care professionals is not recommended unless there is intimate exposure to a patient with invasive meningococcal disease because a measurable attack rate has not been documented among such personnel. This type of exposure would include unprotected mouth-to-mouth resuscitation, intubation, or suctioning of the patient before antimicrobial therapy was administered.

10. (C) Most coagulase-negative staphylococci (CoNS) isolated from blood cultures are common inhabitants of the skin and mucous membranes and are procedural contaminants of blood culture techniques. Risk factors for actual CoNS infection would include catheter placement, medical device insertion, or immunosuppression. CoNS are common causes of ventriculoperitoneal shunt infections, but secondary bacteremia or bacteremic seeding of the shunt does not occur. CoNS may also cause urinary tract infections, particularly in adolescent girls and young adult women. The species involved is most commonly S saprophyticus. Children with fever and neutropenia who have CoNS bacteremia most often have central venous catheters in place.

11. (E) Toxic shock syndrome (TSS) can be caused by toxin-producing S aureus or S pyogenes stains. In children a major risk factor for streptococcal TSS is concomitant varicella. Both etiologies of TSS can occur without an identifiable focus of infection (Table 103-1).

12. (D) According to CDC recommendations, all pregnant women should be screened at 35-37 weeks’ gestation for rectal and vaginal colonization for GBS. Intrapartum prophylaxis is indicated if there was a previous infant with invasive GBS disease, if the GBS screening culture is positive during the current pregnancy, or if the temperature is more than 100.4°F (38°C) with unknown GBS status. Colonization alone during a previous pregnancy is not an indication for intrapartum chemoprophylaxis unless screening results are positive in the current pregnancy.

TABLE 103-1 Features of Toxic Shock Syndrome Caused by Staphylococcus Aureus and Streptococcus Pyogenes (Gas)

 

FEATURE

STAPHYLOCOCCUS AUREUS

STREPTOCOCCUS PYOGENES

 

Prodrome

Vomiting, diarrhea

Malaise, myalgia

Physical findings

   

Rash

Diffuse macular erythroderma

Generalized erythematous macular rash

Conjunctivitis

Often present

Absent

Soft tissue infection

Uncommon

Common

Foreign body at infection site

Common

Uncommon

Necrotizing fasciitis

Yes

Yes

Can be inciting infection

   

Recurrent episodes

Yes

No

Toxin

TSST-1, enterotoxins

SPE A, SPE B

Abbreviations: TSST-1, toxic shock syndrome toxin-1; SPE, streptococcal pyrogenic exotoxin.

13. (A) The enterococcus can cause neonatal infections as well as occasional infections in older children. In older children nosocomially acquired infection is not rare. Risk factors include indwelling central venous catheters, GI disease, immunodeficiency, cardiovascular abnormalities, and hematologic malignancy. Enterococcus spp. can occasionally cause meningitis, usually in neonates, and can occasionally cause urinary tract infections.

14. (E) In patients with disseminated gonococcal infection, isolation of N gonorrhoeae from a sterile site such as blood or joint fluid occurs in less than half of the patients. However, the organism can be isolated from a mucosal site or from a sexual contact in approximately 80% of cases. Ribosomal RNA detection is in wide use and has comparable sensitivity and specificity to the culture.

15. (B) A bite by a cat or a dog that results in cellulitis within 24 hours of the bite is most likely caused by Pasteurella multocida. Regional lymphadenopathy, fever, and chills are common. Tenosynovitis, septic arthritis, or osteomyelitis can also occur, associated with deeper bites by animals. Eikenella is an occasional culprit.

16. (D) Antimicrobial therapy is not indicated for uncomplicated Salmonella gastroenteritis in most cases because the therapy does not shorten the duration of disease and may prolong carriage. Children younger than 5 years have prolonged shedding with 40% excreting Salmonella in the stool for 20 weeks after onset of illness. Antimicrobial therapy for Salmonella gastroenteritis is indicated for certain groups of patients, including infants younger than 3 months as well as patients with chronic GI disease, malignancy, hemoglobinopathy, HIV infection or other immune deficiency or severe colitis.

17. (A) Even though the stool culture is negative for bacterial pathogens, Shigella is still the most likely pathogen. The sensitivity of stool culture for diagnosing Shigella dysentery in approximately 70%. Treatment for patients with Shigella is recommended for patients with severe illness or bacteremia, dysentery, or immunodeficiency.

18. (B) Infection caused by Yersinia is caused by ingestion of contaminated foods (pork intestine, milk, and other dairy products), by contaminated surface or well water, by direct or indirect contact with animals, or refrigerated stored blood. Infections in humans are more common in cooler climates during the winter months. Most likely, a caretaker handled the chitterlings and transmitted the pathogen to the infant. Y enterocolitica has also been reported to cause mesenteric adenitis, septicemia, meningitis, and postinfectious sequelae such as reactive arthritis, erythema nodosum, and uveitis.


SUGGESTED READING

Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008.

Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med. 2005;352:1445-1453.

Pickering LK, Baker CJ, Kimberlin DW, Long SS: Red Book2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

CASE 104: A 13-YEAR-OLD ADOLESCENT BOY WITH A CHRONIC COUGH

A 13-year-old adolescent boy, who has been previously healthy, is brought to your office because he has had a persistent daytime and nighttime cough for the past 6 weeks. He had been diagnosed with pneumonia 4 weeks ago and treated with a 5-day course of azithromycin, then a 10-day course of amoxicillin-clavulanic acid, but there was little improvement. In addition, he has developed intermittent chest pain and a sensation of fever. He now has blood-tinged sputum.

On physical examination he is alert and cooperative. He is nontoxic in appearance. The temperature is 100°F (37.8°C). There are no skin lesions present. There is mild anterior and posterior cervical lymphadenopathy. The respiratory rate is 30/minute. The lung examination revealed decreased breath sounds over the left anterior and posterior chest. The examination of the heart and abdomen is normal.

SELECT THE ONE BEST ANSWER

1. A chest radiograph is obtained, which reveals increased density in the inferior segment of the left lower lobe and marked interstitial disease in the left lower and right upper lobes. The left upper lobe is partially collapsed. A fungal culture of the sputum reveals no mycelia forms on smear, but the culture grows a few colonies of Blastomyces dermatitidis. The most common extrapulmonary manifestation of blastomycosis involves the

(A) skin

(B) bone and joints

(C) genitourinary tract

(D) heart

(E) CNS

2. An 8-year-old girl from Indiana develops fever, cough, malaise, and chest pain. A chest radiograph reveals diffuse reticulonodular infiltrates with hilar adenopathy. You obtain the history that she was playing in a barn 2 weeks before the illness started. The most likely etiology of the child’s illness is

(A) B dermatitidis

(B) Histoplasma capsulatum

(C) Mycobacterium tuberculosis

(D) Paracoccidioides brasiliensis

(E) Coccidioides immitis

3. A 15-year-old girl develops a papule on the dorsum of her left hand that in a 2-week period enlarges and becomes indurated. The skin lesion then develops into a painless ulcer with formation of subcutaneous nodules and erythema involving the forearm. There is no response to antibacterial therapy. The most likely diagnosis is lymphocutaneous

(A) nocardiosis

(B) blastomycosis

(C) aspergillosis

(D) tuberculosis

(E) sporotrichosis

4. A 14-year-old girl develops fever to 102°F (38.8°C), chest pain, and rash 2 weeks after returning from visiting relatives in Phoenix, Arizona. She took a few trips to desert areas outside Phoenix while visiting. On physical examination, she has fever of 102°F (38.8°C), and erythema nodosum is present on the lower extremities. A chest radiograph reveals a small right middle lobe infiltrate. Of the following, the pneumonia is most likely caused by

(A) Aspergillus fumigatus

(B) Histoplasma capsulatum

(C) Candida glabrata

(D) Coccidioides immitis

(E) Blastomyces dermatitidis

5. Congenital candidiasis can occur both in term and premature infants. The clinical manifestations in these two groups of patients differ in all the following features except

(A) premature infants require treatment with amphotericin B

(B) premature infants are more likely to have pulmonary involvement

(C) premature infants with candidiasis more often have a positive blood culture

(D) premature infants more often have a leukemoid reaction

(E) at birth both term and preterm infants have a diffusely erythematous popular rash

6. A 7-year-old white girl has multiple hyperpigmented brown lesions with scaling that involve the upper trunk, proximal trunk, and neck. These are also a few scattered hypopigmented macular lesions on the face with fine scaling. You suspect Pityriasis versicolor. The etiologic agent of this skin disorder is

(A) Malassezia furfur

(B) Microsporum canis

(C) Trichophyton tonsurans

(D) Epidermophyton floccosum

(E) Trichophyton rubrum

7. An 8-year-old boy develops fever, headache, cough, and dyspnea. A chest radiograph reveals diffuse interstitial infiltrates. He is treated with oral antibiotics (amoxicillin-clavulanate) for 1 week without improvement. Fever and headache persist. He then becomes somnolent and confused. A spinal tap is performed that shows a high protein concentration, low glucose concentration, and pleocytosis, mostly lymphocytes. The diagnosis of cryptococcal meningitis is confirmed by cryptococcal antigen testing of the CSF. The boy likely has an underlying disorder involving

(A) humoral immunity

(B) cell-mediated immunity

(C) complement deficiency

(D) phagocytic function of neutrophils

(E) combined cell-mediated and humoral immunity

8. A 6-month-old infant boy develops progressive respiratory distress with tachypnea and intercostal retractions but no fever. Bilateral rales are heard on auscultation. The infant has hypoxia with an oxygen saturation of 89% and requires intubation. The diagnosis of P jiroveci is confirmed by a fluoresceinconjugated monoclonal antibody stain of a tracheal aspirate specimen. All of the following drugs can be used alone for treatment of P jiroveci except

(A) atovaquone

(B) clindamycin

(C) pentamidine isethionate

(D) trimetrexate-leucovorin

(E) trimethoprim-sulfamethoxazole

9. A 3-year-old girl who lives in a large urban city develops fever to 102°F (38.8°C), irritability, and drowsiness in a 2-week period. The child then develops vomiting, lethargy, and nuchal rigidity. A CT scan of the brain shows hydrocephalus and a ventriculoperitoneal shunt is placed. The CSF shows a cell count of 500/mmwith a lymphocyte predominance. The protein concentration was 85 mg/dL and the glucose level was 40 mg/dL. A chest radiograph is normal, and the Mantoux test is nonreactive. The child’s mother reveals that she and her daughter have been living in a homeless shelter for the past 6 months. The most likely diagnosis is

(A) cryptococcal meningitis

(B) neurocysticercosis

(C) Baylisascaris meningoencephalitis

(D) lymphocytic choriomeningitis

(E) tuberculous meningitis

10. A full-term newborn infant boy is born to a 23-yearold mother who has a positive Mantoux test reaction, a result obtained 1 week before delivery. The infant should be evaluated for congenital tuberculosis in all of the following circumstances except when the

(A) mother has miliary tuberculosis

(B) mother has tuberculous endometritis

(C) mother has tuberculous infection of the knee joint

(D) mother has apical scarring of the right upper lobe of the lung with a negative sputum smear for acid-fast bacilli

(E) mother has active pulmonary tuberculosis

11. A 4-year-old boy with HIV infection has a CD4 count of 80 cells/mm(3%). He has a fever of 102°F (38.8°C) that persists for 1 week and is associated with weight loss, abdominal pain, fatigue, and diarrhea. Anemia is present with a hemoglobin of 9.0 g/dL. The most likely infectious etiology to explain these findings is

(A) nontuberculous mycobacteria, disseminated

(B) Bartonella henselae, disseminated

(C) M tuberculosis, disseminated

(D) brucellosis, disseminated

(E) histoplasmosis, disseminated

12. A 3-year-old girl has a 1-month history of bilateral swelling of the submandibular lymph nodes. There is no history of fever, fatigue, or weight loss. A chest radiograph is normal and a Mantoux test result is positive at 10 mm. All of the following are consistent with nontuberculous mycobacterial lymphadenitis except

(A) age of the patient

(B) involvement of bilateral lymph nodes

(C) normal chest radiograph

(D) size of Mantoux test response

(E) lack of systemic symptoms

13. A 2-year-old boy who attends a child-care center develops diarrhea that persists for 2 weeks and is associated with malaise, anorexia, abdominal distension, and abdominal cramps. You suspect giardiasis as the etiology. All of the following methods can be used to diagnose Giardia lamblia infection except

(A) duodenal fluid specimen

(B) concentrated specimen of stool

(C) DFA test of stool

(D) IgG-specific serum antibody to Giardia by enzyme immunoassay

(E) enzyme immunoassay to detect stool antigen

14. Toxoplasmosis can cause both congenital infection and acquired infection in older children and adults. The most common physical finding in children with acquired toxoplasmosis is

(A) splenomegaly

(B) pharyngitis

(C) conjunctivitis

(D) macular rash

(E) lymphadenopathy

15. A 16-year-old sexually active adolescent female presents to your office with a 1-week history of vaginal discharge and dysuria. She also reports a recent history of dyspareunia. A pelvic examination reveals vaginal and vulvar erythema with a frothy discharge. The cervix has a “strawberry appearance,” related to friability and punctate hemorrhages. Based on these findings, you strongly suspect infection with

(A) Chlamydia trachomatis

(B) Gardnerella vaginalis

(C) Neisseria gonorrhoeae

(D) Trichomonas vaginalis

(E) Haemophilus ducreyi

16. A 3-year-old boy develops fever and malaise in a 10-day period. On physical examination he has a fever of 102°F (38.8°C) and hepatosplenomegaly. The leukocyte count is 9000/mmwith 50% eosinophils (4500/mm3). An important epidemiologic finding to support the diagnosis of visceral larva migrans (VLM) caused by Toxocara canis is

(A) recent visit to a cave

(B) recent play in a sandbox

(C) recent play in a barn

(D) family has two adult dogs as pets

(E) consumption of raw or undercooked meat

17. The different Plasmodium species that cause malaria have unique geographic distribution and resistance patterns. The following statement regarding the clinical features and epidemiology of malaria is correct

(A) P ovale infections are common only in South Africa

(B) P vivax malaria is prevalent on the Indian subcontinent and in Central and South America

(C) P malariae has the same geographic distribution as P falciparum and is more common in most areas they coinhabit

(D) relapses can occur in P malariae infection because of a persistent hepatic stage of infection

(E) most deaths worldwide from malaria occur in adolescents

18. A 4-year-old girl returns from a trip to Bangladesh with her family where they traveled for the past 3 months. She develops diarrhea that persists for 2 weeks before being brought to your office by her parents. There is a history of bloody stools associated with abdominal pain. You suspect intestinal amebiasis. An important extraintestinal complication of Entamoeba histolytica infection you should consider is

(A) ameboma

(B) liver abscess

(C) brain abscess

(D) cutaneous amebiasis

(E) genitourinary tract involvement

ANSWERS

1. (A) The skin lesions of blastomycosis usually begin as papules that evolve into verrucous, ulcerative lesions (Figure 104-1). Osteomyelitis is the third most common manifestation of disseminated blastomycosis after lung and skin involvement. The CNS can also be involved with meningitis the most common complication.

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FIGURE 104-1. Typical skin lesion of sporotrichosis involving the finger. (Reproduced, with permission, from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill; 2005: 739.)


2. (B) Areas of high incidence of histoplasmosis include the Mississippi and Ohio River Valleys. Some activities of children that can predispose to infection include playing in barns, hollow trees, caves, or bird roosts. Infection is usually selflimited in immunocompetent children, but one form of infection called progressive disseminated histoplasmosis can occur. Prolonged fever, failure to thrive, and hepatosplenomegaly can develop in infants. A chest radiograph can show diffuse reticulonodular infiltrates. This form of the disease is often fatal if untreated.

3. (E) In children, sporotrichosis is localized to the skin and subcutaneous tissue (see Figure 104-1). The disease most commonly affects the face and extremities, in particular the hands and fingers. In most cases, infection will spread to the regional lymph nodes that drain the primary site of infection. Skin lesions associated with tuberculosis include erythema nodosum; papulonecrotic tuberculids that are miliary lesions of the skin, verrucosa cutis, which is a tuberculous wart-like lesion; and scrofuloderma, which is an ulcer or sinus tract resulting from rupture of a lymph node.

4. (D) The travel history and the clinical situation suggest that the patient has coccidioidomycosis. The infection is endemic to Southern California, Arizona, western and southern Texas, and New Mexico. In children with coccidioidomycosis, an acute diffuse erythematous rash and erythema multiforme are common. The primary infection involves the lungs, and, in healthy children, symptoms improve without treatment within a few days to 1 month.

5. (C) In term infants, congenital cutaneous candidiasis is acquired from contaminated amniotic fluid. Skin findings include vesicles, pustules, or a widespread erythematous macular rash. In premature infants the skin findings may resemble a widespread erythematous dermatitis. The skin findings are associated with invasive pulmonary disease and early-onset respiratory distress. Neither form has positive blood cultures for Candida. Skin involvement with Candida can occur after birth and is more often associated with positive blood cultures in premature infants.

6. (A) Malassezia furfur also can cause a chronic folliculitis in immunocompromised persons, such as with acquired immunodeficiency syndrome. In addition, systemic Malassezia infection can cause fungemia in infants receiving parenteral nutrition that contains intralipids. Fever, apnea, and bradycardia, interstitial pneumonia, and thrombocytopenia are common associated findings.

7. (B) Primary infection occurs through inhalation of airborne particles. After inhalation, the organism disseminates from the lungs to other organs, the most important being the CNS. Dissemination of the fungus is rare in children without defects in cellmediated immunity. CD4+ lymphocytes have been shown to play an important role in containing CNS infection caused by Cryptococcus. Infection with Cryptococcus neoformans in the pediatric or adolescent age group should prompt an evaluation for HIV.

8. (B) Trimethoprim-sulfamethoxazole is the drug of choice for treatment. Clindamycin plus primaquine has been used for treatment in adults. Prednisone is recommended as adjunctive therapy for moderate to severe P jiroveci infection.

9. (E) Tuberculous meningitis is most common in children 6 months to 4 years old. Meningitis can occur within 2-6 months of the initial infection. Chest radiographs are normal in 50%, and the Mantoux test is nonreactive in 40% of children with tuberculous meningitis. A CT scan of the brain can be useful to detect basilar enhancement, communicating hydrocephalus, and signs of cerebral edema (Table 104-1). Hydrocephalus secondary to meningeal cysticercosis is rare, and cryptococcal meningitis is also not associated with hydrocephalus. Lymphocytic choriomeningitis virus can cause congenital infection characterized by chorioretinitis, hydrocephalus, and microcephaly. Intracranial calcifications are also typically present. Infection with lymphocytic choriomeningitis virus can also be acquired after contact with mice or hamsters.

10. (D) Congenital tuberculosis is rare. A pregnant woman with isolated pulmonary tuberculosis is unlikely to infect her infant until after birth. If congenital tuberculosis is suspected, a Mantoux test, chest radiograph, and lumbar puncture should be performed and antituberculous therapy started. The placenta should be sent to pathology and cultured for M tuberculosis.

TABLE 104-1 Characteristic Features of Tuberculous Meningitis in Children

 

FINDING

RESULT

 

Exposure

To an adult with tuberculosis

Age

Most common 6 mo to 4 yr

Cranial nerve involvement

III, VI, VII

Mantoux test

Nonreactive in up to 40%

Chest radiograph

Normal in up to 50%

CSF

WBC 10-500/mm3 (mononuclear)

Glucose 20-40 mg/dL, protein >400 mg/dL

CT of brain

Basilar enhancement, communicating hydrocephalus

 

Abbreviations: CSF, cerebrospinal fluid; CT, computed tomography.

11. (A) All of the bacteria listed can cause disseminated infection in children with AIDS, but infection with nontuberculous mycobacteria, particularly M avium complex (MAC), is most common. The risk of developing disseminated MAC infection is inversely related to the CD4+ count. The incidence is as high as 24% in children with CD4+ counts less than 100 cells/mm3. Manifestations of disseminated MAC infections include fever, weight loss, night sweats, abdominal pain, diarrhea, anemia, and neutropenia.

12. (B) Lymphadenitis or scrofula is the most common manifestation of nontuberculous mycobacterium (NTM) infection. Lymphadenitis caused by nontuberculous mycobacteria is usually unilateral and involves the submandibular or anterior cervical lymph nodes. For NTM lymphadenitis in healthy children, complete surgical excision is curative.

13. (D) Although EIA often provides rapid results, this method is not commercially available for Giardia. The other methods listed are more readily available, and examination of a duodenal specimen should be considered when the organism is not found on repeated stool examination but clinical suspicion is high. Infection can occur either by hand to mouth transfer of cysts from feces of an infected person or ingestion of fecally contaminated food or water. Asymptomatic infection is common. Most community-wide epidemics have occurred secondary to a contaminated water supply.

14. (E) Lymphadenopathy is frequently found in the cervical area of the neck. The classic triad of congenital toxoplasmosis is chorioretinitis, cerebral calcifications, and hydrocephalus. Humans develop infection with T gondii in several scenarios. These include consumption of raw or undercooked meat that contains cysts, accidental ingestion of oocysts from soil, contaminated food, or contact with cat feces.

15. (D) T vaginalis is a common sexually transmitted organism. In addition to the signs and symptoms described, abdominal pain can occur. This may indicate severe vaginitis, but pelvic inflammatory disease should also be considered. In males, urethritis occurs with more than half of patients having urethral discharge. Neonates can develop infection after a vaginal delivery. Symptomatic infection in the female neonate involves a self-limited vaginal discharge.

16. (B) In children, infection with T canis begins with ingestion of embryonated eggs. This occurs when children are playing in sandboxes and playgrounds contaminated with cat or dog feces. Other clinical manifestations of VLM include lower respiratory tract symptoms such as bronchospasm that mimics asthma. If the T canis larvae invade the eye, the results is ocular larval migrans (OLM). The retina can be involved with loss of vision. The raccoon roundworm, Baylisascaris procyonis, rarely can cause infection in children, can result in severe encephalitis, and can be acquired from raccoon feces in a sandbox.

17. (B) Each Plasmodium species that causes malaria has a distinct geographic distribution. P ovale occurs most often in West Africa. Malaria attributable to P vivax and P falciparum is common in Southeast Asia, Oceania, and South America. P falciparum is prevalent in Africa, Haiti, and Papua New Guinea. P malariae has the same distribution but is less common than P falciparum. Relapses may occur in P vivax and P ovale because of a persistent hepatic stage of infection.

18. (B) In approximately 10% of patients with invasive Entamoeba histolytica infection, a liver abscess develops. An ameboma is a mass of granulation tissue in the cecum or ascending colon. The clinical presentation usually includes a tender and palpable abdominal mass. Other organ system involvement is uncommon.


SUGGESTED READING

Mandell GL, Bennett JE, Dolin R. MandellDouglas and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010.

Pickering LK, Baker CJ, Kimberlin DW, Long SS. Red Book2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

CASE 105: A 4-YEAR-OLD BOY WITH FEVER AND A NECK MASS

A 4-year-old boy is brought to your office for evaluation of a right-sided neck mass. The child was well until about 10 days ago when he developed fever and a rightsided neck swelling. The swelling has increased in size over the past week and is painful. There has been no cough, sore throat, or rhinorrhea. There has not been contact with anyone who has been ill. There also has not been any history of travel.

On physical examination the child is alert, active, and nontoxic in appearance. The temperature is 102.7°F (39.3°C). There are 3 × 4 cm and 1 × 2 cm right posterior cervical triangle lymph nodes. The nodes are movable, firm, and tender to palpation. There are no skin lesions. Examination of the heart and lungs is normal. The leukocyte count is 8900/mm3, the hemoglobin is 9.5 g/dL, and the platelet count is 300,000/mm3.

SELECT THE ONE BEST ANSWER

1. In obtaining further history you find out there has been no contact with an adult who has a chronic cough or any exposure to ticks or rabbits. The mother does tell you that their family cat had kittens about 3 months ago. The most likely etiologic agent of this child’s illness is

(A) Bartonella henselae

(B) Blastomyces dermatitidis

(C) Francisella tularensis

(D) Mycobacterium tuberculosis

(E) Toxoplasma gondii

2. The diagnosis in this 4-year-old child can be confirmed most readily by

(A) culture of blood

(B) culture of lymph node specimen

(C) special stains of lymph node specimen

(D) serology

(E) an antigen skin test

3. Treatment of the infection in this 4-year-old should include

(A) surgical excision of the lymph nodes

(B) no antimicrobial therapy

(C) doxycycline by the oral route

(D) cefazolin

(E) parenteral gentamicin

4. Endoscopy is performed on a 10-year-old girl with persistent epigastric abdominal pain and vomiting. A duodenal ulcer is found. Infection with Helicobacter pylori is confirmed by culture and histologic examination of duodenal biopsy samples. Treatment for this girl should include which of the following?

(A) omeprazole

(B) omeprazole and metronidazole

(C) clarithromycin and lansoprazole

(D) amoxicillin, clarithromycin, omeprazole, and bismuth subsalicylate

(E) amoxicillin, clarithromycin, and omeprazole

5. A 5-year-old boy returns from Mexico with family after visiting with relatives that lived in a rural area. He has a fever of 103°F (39.4°C), anorexia, and decreased activity 2 weeks after returning home. His mother reports that he does not want to walk. On physical examination there is limitation of movement, swelling, and tenderness of the left knee joint. He also has splenomegaly. A definitive diagnosis can be made by

(A) culture of blood

(B) enzyme immunoassay on acute serum

(C) PCR of serum

(D) urine for antigen detection

(E) serum antibody by enzyme immunoassay

6. A 14-year-old boy develops severe conjunctivitis with pain followed by the development of enlarged painful preauricular lymph nodes. He reveals that 1 week ago he went hunting with his father and killed a number of squirrels. Which of the following should be considered in the differential diagnosis of the adolescent’s illness?

(A) Coccidioides immitis

(B) Francisella tularensis

(C) Bartonella quintana

(D) Mycobacterium tuberculosis

(E) Anaplasma phagocytophilum

7. Kingella kingae can be a normal inhabitant of the oropharynx of humans. The most common clinical infection caused by K kingae in children is

(A) endocarditis

(B) intervertebral diskitis

(C) occult bacteremia

(D) pneumonia

(E) septic arthritis

8. Legionella pneumophila can rarely cause community-acquired pneumonia in healthy children, and infection usually resolves without treatment. However, Legionella pneumophila is likely to cause severe and fatal disease in children with

(A) neoplasm receiving chemotherapy

(B) chronic persistent asthma

(C) X-linked agammaglobulinemia

(D) IgA deficiency

(E) cyanotic congenital heart disease

9. A 7-year-old girl from North Carolina develops fever to 102°F (38.8°C) in July associated with severe headache and myalgias. On the fifth day of fever the child develops a macular blanching rash that starts on the wrists, ankles, and forearms (Figure 105-1). The rash then spreads centrally over the next 24 hours, and scattered petechiae are noted. Laboratory evaluation reveals a leukocyte count of 12,000/mm3, hemoglobin of 12.0 g/dL, and platelet count of 100,000/mm3. The serum sodium is 130 mEq/L. The etiologic agent of this child’s illness is

(A) Epstein-Barr virus

(B) Neisseria meningitidis

(C) Rickettsia akari

(D) R rickettsii

(E) Anaplasma phagocytophilum

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FIGURE 105-1. See color plates.


10. The treatment of choice for this infection in this 7-year-old girl is

(A) azithromycin

(B) chloramphenicol

(C) doxycycline

(D) rifampin

(E) ceftriaxone

11. An 8-year-old boy has a fever of 102°F (38.8°C) associated with headache, anorexia, and vomiting. He remembers being bitten by a tick 9 days before his illness. On physical examination, he is alert. The temperature is 102°F (38.8°C), and a blanching macular rash involving the trunk is present. The leukocyte count is 3500/mm3; the platelet count is 120,000/mm3, the hemoglobin 12 g/dL, and the aspartate aminotransferase (AST) is 110 U/L. The most likely diagnosis is

(A) babesiosis

(B) ehrlichiosis

(C) rickettsialpox

(D) Rocky Mountain spotted fever

(E) leptospirosis

12. The treatment of choice for this infection in this 8-year-old boy is

(A) azithromycin

(B) chloramphenicol

(C) cefepime

(D) gentamicin

(E) doxycycline

13. A 9-day-old male term infant develops a watery eye discharge that becomes purulent. The conjunctiva of the right eye becomes injected and the eyelid is swollen. A DFA test of a conjunctival specimen confirms the diagnosis of C trachomatis infection. Treatment with systemic oral antibiotic therapy is recommended because

(A) there is often coinfection with N gonorrhoeae (B) topical ophthalmic therapy does not eliminate nasopharyngeal carriage

(C) there are no topical ophthalmic antibiotics active against C trachomatis

(D) resistance develops rapidly when ophthalmic antibiotics are used

(E) adherence with ophthalmic antibiotic therapy is less than with oral antibiotic therapy

14. A 5-year-old boy has an illness that includes a 2-week history of cough, sore throat, and fever. The coughing persists, and bilateral rales are heard on auscultation of the lungs. A chest radiograph reveals bilateral infiltrates. The most likely etiology of the following choices for this pneumonia is

(A) Chlamydia pneumoniae

(B) Chlamydia trachomatis

(C) influenza A

(D) Epstein-Barr virus

(E) Histoplasma capsulatum

15. Mycoplasma pneumoniae is a well known to cause lower respiratory tract disease, primarily in schoolage children and young adults. Severe and fatal pneumonia caused by M pneumoniae has been described in children with the following disorder

(A) hypogammaglobulinemia

(B) asthma

(C) cystic fibrosis

(D) prematurity

(E) chronic kidney disease

16. Appropriate antimicrobial therapy for a 5-year-old child with pneumonia caused by M pneumoniae or C pneumoniae is

(A) azithromycin

(B) ciprofloxacin

(C) doxycycline

(D) ceftriaxone

(E) meropenem

17. A 6-year-old boy develops fever, headache, vomiting, and muscle pain. You obtain a history from his mother that he handled a dead rat in the alley of the family’s apartment 2 weeks ago. On physical examination the child has a fever of 102°F (38.8°C) and a maculopapular rash involving the extremities, including the palms and soles. There is no evidence of any bite wound. The causative agent of this child’s illness is likely

(A) Ehrlichia chaffeensis

(B) R rickettsia

(C) Spirillum minus

(D) Streptobacillus moniliformis

(E) Leptospira interrogans

18. The treatment of choice for the infection in the 6-year-old boy just described should include

(A) doxycycline

(B) erythromycin

(C) aztreonam

(D) vancomycin

(E) penicillin

ANSWERS

1. (A) The most common clinical presentation of cat-scratch disease is unilateral regional lymphadenitis. The lymphadenitis usually involves nodes that drain the site of inoculation, but in up to 20% of cases additional lymph node groups are involved (see Figure 105-2). At a particular site of lymphadenitis, multiple nodes are involved about half the time. The most common site is the axilla followed by cervical, submandibular, and inguinal nodes. Most patients with catscratch disease are afebrile. However, systemic catscratch disease can occur in which the presentation includes prolonged fever of 1-3 weeks, malaise, myalgias, and arthralgias. Weight loss, abdominal pain, generalized lymphadenopathy, hepatomegaly, and splenomegaly can occur. Ultrasound of the liver or spleen can identify multiple microabscesses. Encephalopathy is the most serious complication of catscratch disease, occurring in up to 5% of patients.

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FIGURE 105-2. Characteristic regional (axillary) lymphadenopathy in a patient with cat-scratch disease. (Reproduced, with permission, from Fauci AS, Kasper DL, Braunwald E, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill; 2008: Fig. 153-1.)


2. (D) Serology is the method of choice for diagnosis. Both IgG and IgM antibodies to B henselae can be measured. Most patients with catscratch disease have high IgG antibodies at presentation. The IgM test lacks sensitivity. If lymph node tissue is available, the organism may sometimes be seen with the Warthin-Starry silver impregnation stain, but this stain is not specific for B henselae.

3. (B) Surgical excision of lymph nodes is unnecessary. Antimicrobial therapy may be beneficial for severely ill patients with systemic catscratch disease and is recommended for immunocompromised patients. There are two other clinical syndromes of B henselae and B quintana infections reported in immunocompromised patients. Bacillary angiomatosis is a vascular proliferative disorder that involves the skin and subcutaneous tissues and occurs in immunocompromised individuals. Bacillary peliosis occurs primarily in patients with AIDS and is characterized by reticuloendothelial lesions in the liver primarily that can also involve the spleen, abdominal lymph nodes, and bone marrow. The lesions of these two diseases respond to treatment with erythromycin, doxycycline, or azithromycin.

4. (E) Treatment is recommended only for patients who have a history of, or active peptic ulcer disease, gastric mucosa-associated lymphoid tissue-type lymphoma (MALToma), or early gastric cancer. The most effective regimen in children includes a 2-week, 3-agent therapy that consists of a protein pump inhibitor such as omeprazole or lansoprazole, clarithromycin, and amoxicillin.

5. (A) The child likely has brucellosis with osteoarticular involvement. Childhood brucellosis most often affects the large peripheral joints, including the knees, hips, and ankles. A definitive diagnosis is established by recovery of Brucella species from blood, bone marrow, or other tissues. If brucellosis is suspected, the clinical microbiology laboratory personnel should be informed so blood cultures can be incubated for 4 weeks. A serum agglutination test (SAT) and EIA are also available for diagnosis. It is recommended to send the SAT first and measure antibody titers in serum specimens collected at least 2 weeks apart.

6. (B) The adolescent has a clinical form of tularemia called oculoglandular syndrome that results from conjunctival infection and is acquired from contaminated fingers. F tularensis can be transmitted by direct contact with infected animals, through tick bites, and also by contaminated food or water. The most common clinical manifestation is the ulceroglandular syndrome. This disease manifests as swollen, tender lymph nodes in the inguinal, cervical, or axillary regions that are preceded by painful maculopapular lesions at the portal of entry that develop into an ulcerated lesion (Table 105-1).

7. (E) Osteoarticular infection is the most common clinical infection caused by K kingae in children. Studies have shown that inoculating of joint fluid directly into BACTEC aerobic blood culture bottles increases the likelihood of isolating the bacteria. Most infections occur in children younger than 5 years of age. K kingae is a common cause of septic arthritis in young children in Israel but has been reported less frequently in the United States.

TABLE 105-1 Clinical Manifestations of Tularemia

 

CLINICAL SYNDROME

COMMENT

 

Ulceroglandular

Most common form; adenitis ± ulcer

Oculoglandular

Nodular conjunctivitis; enlarged painful preauricular nodes

Oropharyngeal

Pseudomembrane-simulating diphtheria; fever; associated with ingestion of contaminated meat, milk, or water

Typhoidal tularemia

High fever; signs of sepsis; hepatosplenomegaly common; ingestion of contaminated food; can have necrotic lesions in bowel

Gastrointestinal

Ingestion of contaminated food; persistent diarrhea and abdominal or back pain

 

8. (A) The most important clinical infection caused by L pneumophila in both children and adults is pneumonia. Infections in immunocompromised children such as among those in receipt of anticancer therapy represent the most severe form of the disease in pediatrics. At the other end of the spectrum, Legionella is responsible for 1-5% of community-acquired pneumonia in healthy children and the infection is self-limited. Severe disease with pneumonia and septicemia can also occur in neonates.

9. (D) The child’s clinical presentation is most consistent with Rocky Mountain spotted fever. One must have a high index of suspicion because the signs and symptoms during the prodrome are nonspecific. Other findings in children include irritability, severe abdominal pain, conjunctivitis, preseptal edema, and splenomegaly. The rash of Rocky Mountain spotted fever is absent until the third to fifth day of illness. The rash also typically involves the palms and soles and begins on the wrist (see Figure 105-3). The rash is the hallmark feature of the disease but may not occur in up to 20% of cases. North Carolina is the most frequent geographic locale for this misnamed disease.

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FIGURE 105-3. Rocky mountain spotted fever. These erythematous lesions will evolve into a petechial rash that will spread centrally. (Reproduced, with permission, from Knoop KJ, Stack LB, Storrow AS, et al. Atlas of Emergency Medicine, 3rd ed. New York: McGraw-Hill; 2010:372. Photo contributor: Daniel Noltkamper, MD.)


10. (C) Doxycycline is the drug of choice, even in children younger than 8 years. Tetracycline staining of teeth is dose related and unlikely to occur with a single therapeutic course; doxycycline is less likely than other tetracyclines to stain teeth; and use of the alternative antibiotic chloramphenicol has significant potential toxicity. In addition a retrospective study indicates that chloramphenicol may be less effective than doxycycline for treatment of Rocky Mountain spotted fever.

11. (B) In children most cases of ehrlichiosis have been associated with E chaffeensis, which causes human monocytic ehrlichiosis. Most human monocytic ehrlichiosis infections occur in people from southeastern and south central United States, but cases of ehrlichiosis have been reported in 48 states. A closely related infection with similar clinical manifestations and course of illness is human granulocytic anaplasmosis, caused by Anaplasma phagocytophilum. Pediatric cases have a male predominance, and the peak incidence occurs from May to August. The most common symptoms reported in children include fever, myalgia, and rash. Lymphopenia, thrombocytopenia, and increased serum AST are common.

12. (E) Treatment with doxycycline should continue until at least 3 days after defervescence for a minimum of 5-10 days.

13. (B) The risk that a neonate will acquire C trachomatis is 50% if the mother has a chlamydial infection. The risk for neonatal conjunctivitis is 25-50% and for pneumonia is 5-20%. Pneumonia caused by C trachomatis occurs at 2-10 weeks of age. A staccato cough, tachypnea, and rales are characteristic. Wheezing is typically absent. A chest radiograph reveals bilateral interstitial infiltrates and hyperinflation. A diagnostic clue may be the presence of peripheral blood eosinophilia (>400 cells/mm3).

14. (A) Chlamydia pneumoniae causes communityacquired pneumonia, prolonged cough illness, and acute bronchitis in children. The organism has been implicated as the cause in 5-10% of community acquired pneumonias in children. The illness tends to have a subacute presentation that is indistinguishable from that caused by Mycoplasma pneumoniae. Cough is often prolonged with persistence for 2-6 weeks, and the illness can have a biphasic course. Diagnosis can be confirmed by serologic testing, with the microimmunofluorescent antibody test the most sensitive and specific test available.

15. (A) In patients with an underlying immunodeficiency (particularly hypogammaglobulinemia), sickle cell disease, Down syndrome, and chronic pulmonary and cardiac disorders, severe pneumonia with pleural effusion can occur. Infection with M pneumoniae has been best described as an influenza-like illness with gradual onset. Many extrapulmonary manifestations have been ascribed to M pneumoniae. The detection of M pneumoniae DNA by PCR has suggested a role for it in extrapulmonary manifestations such as encephalitis, transverse myelitis, pleural effusion, and bacteremia. M pneumoniae has also been implicated as a cause of Stevens-Johnson syndrome.

16. (A) The newer macrolide and azalide antibiotics are as effective as erythromycin in achieving clinical and microbiologic cure in children with communityacquired pneumonia caused by M pneumoniae. Doxycycline is also effective and can be used for children 8 years and older.

17. (D) Rat bite fever in the United States is mainly caused by S moniliformis. Nonsuppurative migratory polyarthritis or arthralgias occur in 50% of patients. Generalized adenopathy also occurs. Rat bite fever caused by the spirochete S minus manifests with fever and ulceration at the site of the bite. Regional lymphadenitis and lymphadenopathy are associated with the illness. S minus infection occurs primarily in Asia.

18. (E) Penicillin is the drug of choice for rat bite fever caused by either organism. Alternative drugs include ampicillin, cefuroxime, and cefotaxime. Doxycycline can be used in penicillin-allergic patients who are 8 years of age or older.


SUGGESTED READING

Pickering LK, Baker CJ, Kimberlin DW, Long SS. Red Book2009

Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009. Schutze GE, Buckingham SC, Marshall GS, et al. Human monocytic ehrlichiosis in children Pediatr Infect Dis J. 2007; 26:475-479.

CASE 106: A 2-YEAR-OLD GIRL WITH ABDOMINAL PAIN AND FEVER

A 2-year-old girl presents to the children’s hospital emergency department with abdominal pain and fever. The child was well until 5 days ago when she developed fever. The next day abdominal pain began. The abdominal pain persisted and was then associated with intermittent vomiting. The child was otherwise healthy with no previous hospitalizations, operations, or serious medical illnesses. One month previously, she received a 10-day course of amoxicillin for otitis media.

On physical examination the child is ill-appearing and seems to be in pain. Her temperature is 104°F (40°C). There are no skin lesions. Examination of the lungs and heart is normal. There is mild abdominal distention and diffuse abdominal tenderness. A leukocyte count is 28,000/mmwith 60% PMNS, 15% basophils, and 25% lymphocytes. The hemoglobin is 9.8 g/dL, and the platelet count is 18,000/mm3.

SELECT THE ONE BEST ANSWER

1. In this 2-year-old previously healthy child, an abdominal ultrasound is performed that demonstrates free fluid in the abdomen. You suspect primary peritonitis. The most likely etiologic agent in this setting is

(A) E coli

(B) N meningitidis

(C) S aureus

(D) S pneumoniae

(E) Candida albicans

2. The most common underlying condition associated with primary peritonitis caused by S pneumoniae is

(A) B-cell immunodeficiency

(B) HIV infection

(C) complement deficiency

(D) nephrotic syndrome

(E) common variable immunodeficiency

3. A 3-year-old girl presents with a 1-week history of a mucopurulent vaginal discharge. She has a fever to 103°F (39.4°C) and diffuse abdominal pain. An abdominal ultrasound reveals ascites. The most likely cause of these symptoms is primary peritonitis. The most likely pathogen is this setting is

(A) Chlamydia trachomatis

(B) Haemophilus influenzae

(C) Candida tropicalis

(D) S aureus

(E) Neisseria gonorrhoeae

4. The most common complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis. The most common organism responsible for peritonitis in this setting is

(A) Candida albicans

(B) Mycobacterium tuberculosis

(C) Pseudomonas aeruginosa

(D) Staphylococcus epidermidis

(E) Enterococcus faecalis

5. During January, a 12-month-old male infant has a fever of 104°F (40°C). The physical examination is normal and the leukocyte count is 20,000/mm3. All of the following are characteristics of occult bacteremia caused by S pneumoniae except

(A) age 3-36 months

(B) fever 39°C (102.2°F) or higher

(C) WBC count more than 15,000/μL

(D) occurrence in winter season

(E) absence of clinical signs of focal infection

6. In a 2-month-old infant the most likely cause of bacteremia without focality is

(A) Neisseria meningitidis

(B) Streptococcus agalactiae (group B streptococcus)

(C) Streptococcus pyogenes

(D) S aureus

(E) E coli

7. A 21/2-year-old boy has a fever of 103°F (39.4°C) that persists for 6 days. His mother reports that he has become increasingly cranky. He has red eyes and a rash. On physical examination there is fever of 102°F (38.8°C), the child appears fussy, and he has a generalized erythematous maculopapular rash. His blood pressure is normal. He also has bilateral bulbar conjunctivitis with red cracked lips. There is also mild swelling of the hands and feet. The correct therapy for this child would include

(A) IVIG

(B) IV penicillin and clindamycin

(C) IV corticosteroid therapy

(D) oral nonsteroidal anti-inflammatory drug

(E) IV acyclovir

8. A 4-year-old girl has bullous erythema multiforme over the extensor surface of the extremities that then spreads over the trunk. There is bilateral bulbar conjunctivitis, and the lips are swollen, denuded, and bleeding. You suspect Stevens-Johnson syndrome. The infectious agent most clearly established as a cause of this disorder is

(A) herpes simplex virus

(B) M pneumoniae

(C) adenovirus

(D) S pyogenes

(E) H capsulatum

9. A 10-year-old boy has daily documented fever of 100.4°F (38.0°C) or higher for 14 days. All of the following infectious causes should be considered if there is history of travel outside of the United States except

(A) dengue fever

(B) brucellosis

(C) malaria

(D) Salmonella serotype Typhi (typhoid fever)

(E) catscratch disease

10. Children with fever of unknown origin (FUO) have infection as the etiology in more than a third of the cases. The etiology of an FUO in children may be an uncommon presentation of a common infection. This would include all except

(A) endocarditis

(B) pneumonia

(C) sinusitis

(D) urinary tract infection

(E) infectious mononucleosis

11. In children with FUO the likelihood of establishing a diagnosis is low in patients with a normal laboratory value for

(A) amylase

(B) erythrocyte sedimentation rate (ESR)

(C) ferritin

(D) platelet count

(E) reticulocyte count

12. Some children have episodic fevers with fever-free intervals. All of the following are examples of this pattern of recurrent fevers except

(A) cyclic neutropenia

(B) hyper-IgD syndrome

(C) tumor necrosis receptor–associated periodic fever syndrome

(D) Kikuchi-Fujimoto disease

(E) periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA syndrome)

13. Systemic infections are the most common causes of generalized lymphadenopathy. All of the following organisms have a characteristic association with generalized lymphadenopathy except

(A) Ehrlichia chaffeensis

(B) Epstein-Barr virus

(C) human herpes virus type VI

(D) Yersinia enterocolitica

(E) HIV

14. A 7-year-old girl develops migratory arthritis that first involved the left knee and then the right elbow. There is no history of antecedent illness. On physical examination the child is febrile with temperature of 102°F (38.8°C). The right elbow is red, swollen, and tender with movement. The lung and cardiovascular examinations are normal. The ESR is 60 mm/hour. A throat culture reveals the organism depicted in Figure 106-1. The most likely diagnosis of the following choices is

(A) septic arthritis

(B) reactive arthritis

(C) serum sickness

(D) systemic lupus erythematosus

(E) acute rheumatic fever

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FIGURE 106-1. See color plates.


15. A 33-week-gestation newborn infant boy is born to a 19-year-old mother who has not received prenatal care. The mother admits that she used cocaine during the pregnancy. At birth, the infant has a generalized maculopapular rash, splenomegaly, and a slightly distended abdomen. The infant has anemia (hemoglobin of 11.0 g/dL), and urinalysis reveals 3+ protein. The CSF is normal, as is an eye examination. An HIV enzyme immunoassay and nontreponemal test for syphilis (RPR) are negative on the infant. The most likely diagnosis is

(A) HIV infection

(B) congenital CMV

(C) congenital syphilis

(D) congenital toxoplasmosis

(E) congenital rubella syndrome

16. A 10-year-old girl has a fever of 102°F (38.8°C) and a swollen, tender left knee joint 4 weeks after returning to school in the fall. There is also pain and limitation of movement of the joint. She visited relatives in Northern California in July about 3 months ago. Neither she nor her parents recall an illness when visiting in California. You suspect arthritis, a manifestation of late disseminated Lyme disease. The diagnostic test of choice to confirm the diagnosis is

(A) culture of joint fluid for Borrelia burgdorferi

(B) EIA on serum for B burgdorferi IgG antibody

(C) PCR on serum to detect B burgdorferi DNA

(D) urine antigen detection for B burgdorferi

(E) culture of blood for B burgdorferi

17. Of the following, the most appropriate antibiotic for treatment of Lyme arthritis in the 10-year-old girl is

(A) azithromycin

(B) ceftriaxone

(C) amoxicillin

(D) trimethoprim-sulfamethoxazole

(E) doxycycline

ANSWERS

1. (D) S pneumoniae is the most common cause of primary peritonitis in children with no underlying immune or anatomic defect. Less common causes include other gram-positive organisms (S aureus, group B streptococcus) and a variety of gramnegative organisms such as E coli and Klebsiella species. N meningitidis and N gonorrhoeae primary peritonitis has also been reported (Table 106-1).

TABLE 106-1 Classification and Etiology of Peritonitis in Children

 

CLASSIFICATION

SETTING

ETIOLOGIC AGENTS

 

Primary

Intact gastrointestinal tract

1. Bacteremia

2. Nephrotic syndrome/cirrhosis

3. VP shunt/CAPD

4. Vaginitis

5. Tuberculosis

1. Spn, S aureus, GBS

2. Spn, enteric GNB

3. S aureus, CONS

4. N gonorrhoeae

5. M tuberculosis

Secondary

Defect or rupture of gastrointestinal tract

1. Ruptured appendix, perforation of small or large bowel

2. Perforation of stomach

1. Enteric GNB, enterococcus, and anaerobes

2. Upper respiratory tract and aerobic bowel flora, Candida spp.

   

Abbreviations: CAPD, continuous ambulatory peritoneal dialysis; CoNS, coagulase negative staphylococci; GBS, Group B streptococcus; GNB, gram-negative bacilli; Spn, Streptococcus pneumoniae; VP, ventriculoperitoneal.

2. (D) The serum opsonizing activity of children with nephrotic syndrome is decreased. Children with nephrotic syndrome are at greatest risk for pneumococcal sepsis and peritonitis when in relapse and spilling large amounts of protein, which includes factor B of the alternative complement pathway. Children with nephrotic syndrome can also have low serum IgG levels.

3. (E) Prepubertal children with gonococcal vaginitis can develop peritonitis. The diagnosis can be confirmed by culture of the vagina for N gonorrhoeae. In this circumstance an evaluation for sexual abuse must be undertaken.

4. (D) Gram-positive organisms including S epidermidis and S aureus account for 50% of episodes. Gram-negative organisms account for 20% and fungal peritonitis occurs in 2% (Table 106-1). The classic triad of peritonitis in CAPD is fever, abdominal pain, and cloudy peritoneal dialysis fluid.

5. (D) There is no one historical item or diagnostic test that will identify all children with occult bacteremia. Fever higher than 103.1°F (39.5°C), age 3-36 months, and a leukocyte count more than 15,000/mmincrease the risk of occult bacteremia. The most common etiology of occult bacteremia is S pneumoniaeH influenzae type b was the second most common cause but has been virtually eliminated with the routine immunization of infants with H influenzae type b conjugate vaccine. N meningitidis infection can also cause occult bacteremia.

6. (B) Late-onset disease caused by S agalactiae should be considered as a cause of bacteremia without focality in infants younger than 3 months of age. Meningitis is the most serious complication that can complicate bacteremia, but osteomyelitis, arthritis, cellulitis, or adenitis can occur. Some of these infections without focality have occurred in very low birthweight infants after a prolonged hospitalization. This clinical manifestation of group B streptococcus has been termed very late-onset infection.

7. (A) The child fulfills the “classic” diagnostic criteria for Kawasaki disease with fever persisting at least 5 days plus the presence of at least 4 of 5 designated clinical criteria. These include bilateral bulbar conjunctival injection, changes of the lips and oral cavity, erythema and swelling of the hands and feet, and an erythematous rash (see Figure 106-2). One feature the child did not have was one or more enlarged lymph nodes larger than 1.5 cm in diameter.

In the presence of four or more criteria, the diagnosis of Kawasaki disease can be made on day 4 of illness. The diagnosis should be considered in a young child with fever 5 days or longer and any of the principal clinical features of the disease. An algorithm has been developed by the American Heart Association (AHA) and American Academy of Pediatrics (AAP) to aid clinicians in deciding which patients with fever and fewer than four classic criteria should undergo echocardiography and receive salicylate and IVIG treatment for Kawasaki disease. This includes a combination of assessing whether the patient’s characteristics are consistent with Kawasaki disease and assessing laboratory tests including CRP and ESR.

Treatment of Kawasaki disease includes IGIV 2 g/kg given as a single infusion plus an antiinflammatory dose of aspirin, 80-100 mg/kg per day in four divided doses. Retreatment with IGIV is recommended for patients with persistent fever for 48 hours after the initial infusion or recurrence of fever after an initial period of being afebrile for 48 hours or less.

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FIGURE 106-2. Kawasaki disease. Cherry-red lips with hemorrhagic fissures, in a young boy with prolonged high fever. This child also had a generalized morbilliform eruption, injected conjunctivae, and a “strawberry” tongue (not shown). Note erythema and edema of finger tips. (Reproduced, with permission, from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 6th ed. New York: McGraw-Hill; 2009: Fig. 14-44.)


8. (B) Many infectious agents are associated with the development of erythema multiforme minor (involvement of no more than one mucosal surface). However, M pneumoniae is the most convincingly demonstrated cause of erythema multiforme and Stevens-Johnson syndrome.

9. (E) Brucellosis is prevalent in the Mediterranean basin and the Indian subcontinent as well as Mexico and Central and South America. Malaria occurs in tropical climates, and salmonellosis in the form of typhoid fever usually is related to travel in a developing country in the 6 weeks before illness onset. Bartonella henselae causing catscratch disease occurs sporadically throughout the United States. B bacilliformis occurs in a restricted geographic region in the Andes Mountains in western South America. The acute form is a febrile illness with high mortality and is called Oroya fever. This is a bacteremic illness resulting in severe hemolytic anemia and transient immune suppression.

10. (A) The definition of FUO includes a minimum of 14 days of daily temperature of 100.9°F (38.3°C) or higher with no apparent cause, after performance of repeated physical examinations and screening laboratory tests. Infections account for more than a third of cases of FUO, and in general are common infections with an uncommon presentation. In a recent series of children with FUO, Epstein-Barr virus infection, vertebral and pelvic osteomyelitis, catscratch disease and urinary tract infection were the most common infections described.

11. (B) The likelihood of establishing a diagnosis in a child with FUO is low in patients with a normal ESR and hemoglobin value.

12. (D) Other disorders causing periodic, recurrent, or episodic fevers include relapsing fever caused by Borrelia recurrentis and familial Mediterranean fever. Kikuchi-Fujimoto disease is a histiocytic necrotizing lymphadenitis and is in the differential diagnosis of regional or generalized lymphadenopathy that may present as an FUO but not as a periodic fever syndrome.

13. (D) Many infectious and noninfectious diseases cause generalized lymphadenopathy. Both Salmonella typhi and Y enterocolitica can cause mesenteric lymphadenitis. S typhi can cause hepatosplenomegaly and generalized lymphadenopathy, although the lymphadenopathy of Y enterocolitica is seldom generalized. Generalized lymphadenopathy can occur in association with E chaffeensis, which causes human monocytic ehrlichiosis, a tick-borne disease.

14. (E) The 7-year-old fulfills the Jones criteria for the diagnosis of acute rheumatic fever with one major criterion, polyarthritis, found in approximately 75% of cases and 2 minor criteria (fever and accelerated ESR) along with supporting evidence of antecedent group A streptococcus infection. Figure 106-1 shows a Gram stain of a broth culture obtained from a beta-hemolytic colony from a blood agar plate revealing gram-positive cocci in chains identified as S pyogenes (group A streptococcus). Other major criteria include carditis (50-60% of cases), chorea (10-15% of cases), erythema marginatum (<3% of cases), and subcutaneous nodules (≤1% of cases).

15. (C) The neonate described above with rash and splenomegaly also has nephrotic syndrome and anemia. Nephrotic syndrome occurs in infants with congenital syphilis and is caused by immune complex disease. The negative RPR may be secondary to the prozone phenomenon. This results from excess antibody concentration that inhibits the formation of the antigen-antibody complex that is needed for flocculation. Diluting the same serum and retesting will result is a positive test. The clinical laboratory should be alerted to this possibility. A specific treponemal test such as the FTA-ABS or TP-PA tests should also be positive. Toxoplasmosis is less likely with the normal eye and CSF examinations, and HIV is less likely with the negative HIV EIA. Infants with symptomatic congenital CMV infection will often have neurologic sequelae, including microcephaly, hypotonia, hearing loss, and seizures.

16. (B) The EIA used to detect antibodies against B burgdorferi is usually negative in patients with early localized disease, such as a single erythema migrans lesion. Some patients who are treated early with an antimicrobial agent never develop antibodies against B burgdorferi. Most patients with early disseminated Lyme disease and all patients with late disseminated disease (arthritis is the most common manifestation) have a strong IgG antibody response to B burgdorferi.

17. (E) The antibiotic of choice for late disseminated disease manifesting as Lyme arthritis is doxycycline for children 8 years of age or older or amoxicillin for children younger than 8 years of age. The recommended duration of therapy is 28 days, compared with 14-21 days for early localized disease. Meningitis, or other CNS disease and carditis, with third-degree heart block should be treated with ceftriaxone for 14-28 days.


SUGGESTED READING

Long SS, Edwards KM. Prolonged, recurrent, and periodic fever syndromes. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Infectious Disease. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008:126.

Shapiro ED. Lyme disease. Pediatr Rev. 1998;19:147-154.