Prophylaxis refers to the administration of antibiotics not to treat an existing illness but rather to prevent disease from occurring.
Pediatrics is considered a preventative health care specialty, and there is great interest in the specific times when medications are given for the prevention of infection. In general, prophylaxis involves administration of antimicrobials for a brief and specific time period. This chapter discusses some major prophylaxis issues in pediatrics.
Acute rheumatic fever is the result of a preceding Streptococcus pyogenes (group A streptococcus) infection. Acute rheumatic fever can occur only after an upper respiratory tract infection. It is thought that postinfection antistreptococcal antibodies generated by the host cross-react with antigens in the brain, heart, and synovial tissue.
Because antistreptococcal antibodies can cross-react with any number of organ systems, there are a myriad of presentations of rheumatic fever. It is for this reason that the Jones criteria have been devised for diagnosis.
The diagnosis of acute rheumatic fever (ARF) is made using the Jones criteria. These criteria are divided into major and minor criteria. The diagnosis of
ARF is made when a patient has two major criteria or one major and two minor criteria.
Jones Criteria: Major Criteria
· Carditis. Cardiac involvement in rheumatic fever can affect all areas of the heart, including the myocardium, pericardium, and endocardium. Involvement of the valves is a classic finding in rheumatic heart disease, whereas inflammation of other areas of the heart is more variable. Most cases of valvular disease in rheumatic heart disease involve the mitral or aortic valve. Initial manifestations typically result in valvular insufficiency, with valvular stenosis developing over several decades after initial infection (Fig. 20.1).
· Arthritis. The arthritis of rheumatic fever is frequently migratory, with initially affected joints having resolution of arthritis without deformity as subsequent joints become inflamed. A classic finding of the arthritis of rheumatic fever is the dramatic response to aspirin therapy.
· Chorea. Patients with chorea have uncontrollable writhing movements, often accompanied by extreme emotional liability and the inability to sit still. The one major exception to the Jones criteria in the diagnosis of ARF is Sydenham's chorea, which occurs in about 15% of patients and alone may make the diagnosis of acute rheumatic fever. Because the onset may be several months after the initial pharyngitis, serologic evidence of the proceeding streptococcal infection may have disappeared.
· Erythema marginatum. This is the rash of acute rheumatic fever described as serpiginous macular lesions, primarily on the trunk and extremities.
· Subcutaneous nodules. These rare manifestations of acute rheumatic fever are usually associated with severe carditis and are most commonly located on extensor surfaces of tendons.
Jones Criteria: Minor Criteria
· Laboratory evidence includes elevated acute-phase reactants (sedimentation rate, C-reactive protein) and prolonged P-R intervals on electrocardiogram
The diagnosis of acute rheumatic fever also requires evidence of antecedent group A streptococcal infection, which includes a positive throat culture, positive rapid antigen test, or elevated or rising streptococcal antibody titers.
FIG. 20.1. Chest x-ray showing cardiomegaly and pulmonary edema in child with acute rheumatic fever.
The clinical presentation of pediatric acute rheumatic fever may vary with age. Recent reports have stated that children younger than 5 years of age are more likely to present with arthritis and rash and less likely to have chorea. Carditis may be more severe in younger children with resultant chronic cardiac disease.
Prophylaxis of Rheumatic Fever
Prophylaxis of acute rheumatic fever is given in patients after the diagnosis by Jones criteria. The purpose of prophylaxis is to decrease subsequent group A streptococcal infection, which would result in another antibody response with resultant exacerbation of rheumatic disease. There are three chemoprophylaxis regimens of acute rheumatic fever:
Duration of Prophylaxis
The duration of prophylaxis for rheumatic fever is often debated. Rheumatic fever with carditis and residual heart disease requires prophylaxis for at least 10 years since the last episode of carditis and at least until 40 years of age. Some experts recommend lifelong prophylaxis to protect an already affected heart. In patients with rheumatic fever with carditis but without residual valvular disease, it is recommended that the duration of prophylaxis is 10 years or into adulthood, whichever is longer. For patients with rheumatic fever without carditis, the duration is 5 years or until 21 years of age, whichever is longer.
Anatomic or functional asplenia may increase the risk for sudden sepsis with encapsulated organisms. Children with complex congenital heart disease frequently have accompanying asplenia. Patients with sickle cell anemia are considered functionally asplenic secondary to repeated splenic infarctions. Streptococcus pneumoniae is the most common infection in these children, although Haemophilus influenzae,Neisseria meningitidis, and even Salmonella species are also seen.
Asplenic patients who develop invasive bacterial disease can present initially with fever. There is often rapid progression to septic shock. Petechiae and purpura fulminans, usually seen in meningococcal disease, is not uncommon in asplenic patients with pneumococcal sepsis.
Antibiotic prophylaxis against pneumococcal infections is considered standard of care for all children with asplenia. Oral penicillin V, 125 mg twice daily for children 5 years of age or younger and 250 mg given orally twice a day for children older than 5 years is recommended. In addition to antimicrobial prophylaxis, pneumococcal conjugate and/or polysaccharide vaccines, are indicated. Children with asplenia should also receive the meningococcal polysaccharide vaccine at age 2 years or older. In patients with asplenia, prophylaxis until at least 5 years of age is indicated. Many physicians continue lifelong prophylaxis because the risk for sudden sepsis is decreased but not eliminated. Prophylaxis does not completely eliminate the risk, however, and febrile episodes in patients
with asplenia should always be aggressively evaluated and often presumptively treated.
One of the most feared infectious diseases in pediatrics is bacterial meningitis (see Chapter 11). There is the concern that the index case may cause subsequent colonization and infection in a close contact. The two organisms that cause bacterial meningitis in which prophylaxis is indicated are N. meningitis and H. influenzae.
Chemoprophylaxis for families of a child with N. meningitis is recommended for children who have had close contact with the index case; this includes household contacts and childcare contacts during the previous 7 days. Individuals who have direct exposure to the patient's secretions, such as a boyfriend or girlfriend or caretakers who have participated in mouth-to-mouth resuscitation or deep suctioning, are also candidates for prophylaxis.
Antibiotic Regimens for Prophylaxis of Meningococcal Disease
· Rifampin, 10 mg/kg (max. 600 mg) in children older than 1 month (given twice a day for 2 days)
· Ceftriaxone, 125 mg given intramuscularly for children 12 years of age and younger; 250 mg given intramuscularly for children older than 12 years
· Ciprofloxacin, 500 mg orally in a single dose for patients older than 18 years
In the case of H. influenzae type B meningitis, the risk for secondary disease among unimmunized household contacts younger than 4 years of age is the primary concern. Recommendations for chemoprophylaxis are slightly different from those for N. meningitidis because it centers on protecting household contacts who have not been fully immunized and thus are vulnerable to invasive disease.
If there is a contact in the home of the index case younger than 4 years of age who is incompletely immunized, all household contacts, including the index case, should receive prophylaxis. One can see that this strategy is focused on protecting
the vulnerable patient within the household. If a member of the household is immunocompromised, all occupants receive prophylaxis regardless of the immunization history. Rifampin is not to be given to pregnant women. The prophylaxis regimen is rifampin given once a day in dose of 20 mg/kg up to a maximum of 600 mg. This should be given for 4 days total.
Prevention of Perinatal Group B Streptococcal Disease
Streptococcus agalactiae, or group B streptococcus (GBS), is a major cause of morbidity and mortality in pediatrics. Up to one half of adult women may harbor GBS in their genital tract; antibiotic treatment will not permanently reduce this colonization in adults. At the time of delivery, the bacteria may then colonize the skin of the newborn infant. Although a good percentage of newborns born to colonized mothers themselves become colonized, only a small percentage of these neonates develop invasive disease. Risk factors for invasive GBS disease include premature delivery at less than 37 weeks' gestation, maternal temperature greater than 38°C (100.4°F), and prolonged rupture of membranes greater than 18 hours.
GBS disease is divided into two groups: early onset (first week of life) and late onset (up to 3 months of age). Early-onset disease usually presents within the first 24 hours of life with fever, respiratory distress, and sepsis. It is against early-onset disease that prophylaxis regimen is likely to be most effective.
Maternal treatment before delivery has not been found to decrease maternal colonization; therefore, efforts have focused on treatment of the mother at the time of delivery. The theory behind this strategy is that treatment will temporarily decrease colonization in the mother and decrease subsequent colonization and invasive disease in the newborn.
Intensive efforts have been made to determine the best preventative strategy for perinatal GBS disease. Considerable debate exists about whether prophylaxis should be given to all colonized women or just colonized women who exhibited specific risk factors for neonatal invasive disease. In 2002, the Centers for Disease Control and Prevention revised previous recommendations.
New Recommendations for Prevention of Neonatal Group B Streptococcal Disease
All pregnant women should be screened for vaginal and rectal GBS colonization at 35 to 37 weeks' gestation. For women who have positive cultures, intrapartum antibiotics are given. Women who have negative cultures do not require antibiotic prophylaxis, even if there are risk factors for neonatal GBS infection. The recommended regimen is as follows:
Intrapartum prophylaxis for perinatal GBS infection:
· Penicillin G, 5 million units intravenously ×1, then 2.5 million units every 4 hours
· Cefazolin, 2 g intravenously ×1, then 1 g intravenously every 8 hours
· Clindamycin, 900 mg intravenously every 8 hours
· Erythromycin, 500 mg intravenously every 6 hours
Antibiotic prophylaxis should always use the most narrow spectrum antibiotic possible because there have been reports of increasingEscherichia coli resistance to ampicillin, which may be the result of an increasing number of women getting prophylaxis.
Intrapartum prophylaxis is also indicated in the following situations:
1. A mother who had a previous infant with invasive GBS disease
2. GBS bacteriuria during current pregnancy
3. A woman whose GBS status is unknown and has any of the following:
1. Premature delivery at less than 37 weeks' gestation
2. Prolonged rupture of membranes greater than 18 hours
3. Maternal temperature of greater than 38°C (100.4°F)
Mothers who have positive vaginal and rectal cultures during the current pregnancy and have a planned cesarean section without labor or rupture of membranes do not require intrapartum prophylaxis.
Care of the Newborn after Maternal Prophylaxis
A major issue following maternal prophylaxis is what to do with the newborn. Certainly, an ill-appearing neonate requires a full diagnostic workup and empiric antibiotic therapy. There is ongoing concern about the well-appearing newborn, especially one whose mother has received prophylaxis with antibiotics and thus may have a decrease in the yield of positive blood cultures. Current recommendations suggest that any child born to a mother with suspected chorioamnionitis (i.e., a
fever of greater than 39°C [100.4°F] and two or more clinical or laboratory findings suggesting amniotic fluid infection) requires diagnostic evaluation and empiric antibiotic therapy. All newborns who appear clinically ill should have a lumbar puncture performed. A healthy newborn more than 38 weeks' gestation whose mother received more than 4 hours of prophylaxis may be monitored without laboratory evaluation and discharged after 24 to 48 hours.
Well-appearing premature neonates less than 35 weeks' gestation who have had maternal prophylaxis for more than 4 hours may have a limited evaluation, defined as complete blood count and blood cultures, and then be observed for 48 hours. Newborns more than 35 weeks' gestation whose mothers received less than 4 hours of prophylaxis should have a similar limited evaluation and observation.
The revised guidelines do not cover every conceivable situation faced by a pediatrician or neonatologist. Care must often be individualized based on the history of GBS cultures, a prior history of GBS disease, and the clinical and laboratory evaluation of the particular neonate. Nearly all cases of early-onset GBS disease present in the first days of life; children at risk for invasive disease should certainly be observed for at least 48 hours after delivery.
Madan A, Adams MM, Phillip AG. Frequency and timing of symptoms in infants screen for sepsis: effectiveness of a sepsis-screening pathway. Clin Pediatr 2003;42(1):11–18.
Ottolini MC, Lungren K, Mirkinson LJ, et al. Utility of complete blood count and blood culture screening to diagnose neonatal sepsis in the asymptomatic at risk newborn. Pediatr Infect Dis J 2003;22(5):430–434.
Schrag S, Gorwitz R, Fultz-Butts K, et al. Prevention of perinatal group B streptococcal disease. Revised Guidelines from CDC. MMWR Morb Mortal Wkly Rep 2002;51(RR-11):1–22.
Tani L, Veasy G, LuAnn M, et al. Rheumatic Fever in children younger than 5 years: in presentation different. Pediatrics2003;112(5):1065–1068.
Authors: Janner, Donald
Title: Clinical Guide to Pediatric Infectious Disease, A, 1st Edition
Copyright ÂŠ2005 Lippincott Williams & Wilkins
> Back of Book > Appendix > Color Plates
COLOR PLATE 3.2. Scalp vesicles in a 2-week-old infant representing mucocutaneous herpes infection. (See black and white image.)
COLOR PLATE 7.1. Purpura fulminans in child with overwhelming Neisseria meningitidis infection. (See black and white image.)
COLOR PLATE 9.2. Chronic cervical adenitis seen in atypical mycobacterial infection. (See black and white image.)
COLOR PLATE 16.1. Cellulitis, edema, and bullae formation in child with necrotizing fasciitis. (See black and white image.)