THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

29. Infectious Disease - Joyce E. Broyles, PharmD, BCNSP

29-1. General Principles of Infectious Disease

Introduction

Several infectious disease topics are addressed in other chapters of this review, including common colds in Chapter 27, HIV (human immunodeficiency virus) and acquired immune deficiency syndrome (AIDS) in Chapter 31, and otitis media in Chapter 33. For additional information about specific anti-infective agents, see Chapter 30.

Diagnosis

Diagnosis of most infectious diseases consists of isolation and identification of microorganisms, assessment of patient signs and symptoms, and analysis of other laboratory data.

Isolation of organisms

To identify the causative agent of a disease, samples should be taken from appropriate body sites prior to the initiation of anti-infective therapy. Organisms isolated from body sites that normally are sterile (blood, urine, and spinal fluid) yield higher predictive value than do organisms isolated from body sites that normally are bacteriologically colonized (skin or fecal material).

Identification of organisms

To determine the infectious organism's cell morphology and to guide empiric therapy, one must Gram stain body sites for organisms as soon as possible. After the species of organism has been determined, one should expose it to standardized concentrations of antibiotics to determine the concentrations that inhibit growth. The lowest concentration that prevents microbial growth after 18-24 hours is called the minimum inhibitory concentration (MIC). The three breakpoint concentrations of antibiotics are susceptible, intermediate, and resistant. An antibiotic's breakpoint concentration is determined by considering (1) tissue concentrations with normal dosing and (2) the organism's population distribution. The breakpoint concentration determines whether the antibiotic can be used for therapy.

Physical signs and symptoms of infection (such as fever, redness, swelling, pain, and cough) must be considered both for initial diagnosis and for assessment of antibiotic effectiveness.

Laboratory tests

In the initial stage of infection, the patient's neutrophil count may increase above normal, and immature neutrophil forms (bands) may appear; therefore, a white blood cell (WBC) count should be taken. Later in the course of illness, the neutrophil count may fall to below normal levels.

Inflammatory markers, such as C-reactive protein, erythrocyte sedimentation rate, and tumor necrosis factor, may increase during infection.

Laboratory tests may not be reliable in patients who are elderly, malnourished, neonatal, or severely infected.

Treatment Strategies

Anti-infective agents should be used only when a significant infection has been diagnosed, when one is strongly suspected, or when prophylactic therapy is indicated.

In situations where multiple organisms could be the infecting agent (e.g., pneumonia), empiric therapy should cover the majority of possible organisms, with de-escalation of antimicrobial therapy when the causative agent is discovered.

Prophylactic therapy

Anti-infective therapy is aimed at preventing infection. Prophylactic therapy commonly is used after exposure to infection (e.g., tuberculosis) or before surgical intervention in areas of high bacterial inoculum (e.g., bowel surgery).

Empiric therapy is directed toward all common pathogens associated with a disease state.

Culture-guided therapy, which usually is narrower spectrum than empiric therapy, covers only the specific organism that is sensitive to the therapy. Culture-guided therapy is preferred because it is more cost-effective and because it decreases bacterial resistance from unnecessary antibiotic exposure.

Choice of Anti-infective Agent

To determine optimal anti-infective therapy or to review the appropriateness of other decisions, a clinician must answer several questions:

• Is an antibiotic indicated on the basis of the clinical findings?

• Have appropriate specimens been obtained, examined, and sent for culture?

• What organisms most likely are causing the infection?

• If several antibiotics are available to treat the likely or known organism, which agent is best for the patient? (Patient allergies and concurrent disease states should be considered.)

• Is an antibiotic combination appropriate? (A combination of drugs should be given only when clinical experience has shown such therapy to be more effective than single-agent therapy in a particular setting. Such multiple agent regimens can increase the risk of toxic drug effects; occasionally, they may result in drug antagonism and loss of effectiveness. However, some combinations of anti-infective agents have demonstrated increased effectiveness that is greater than their individual effectiveness combined, a phenomenon known as synergy. An example of synergy is the combination of aminoglycosides with cell wall inhibitors, such as penicillin, in many Gram-positive organisms.)

• What is the best route of administration? (This decision will depend on the overall plan for the patient. Oral therapy is preferred for outpatient therapy; many intravenous anti-infectives have oral forms with similar pharmacokinetic profiles.)

• What is the appropriate dose and dose interval? (Regimen design should take into account patient size, renal or hepatic function, the disease state to be treated, and pharmacodynamic considerations of the agents used.)

• Will initial therapy need modification after culture data are returned?

• What is the optimal duration of therapy, and is the development of resistance during prolonged therapy likely to occur?

Lack of Therapeutic Effectiveness

When anti-infective therapy fails, careful analysis of possible causes should be made prior to changing the regimen. Factors associated with therapeutic failure include misdiagnosis of the infection, improper drug regimen, inappropriate choice of antibiotic agent, and resistance of the infecting agent, as well as situations in which antibiotic therapy may not be effective without additional interventions (e.g., surgical drainage).

29-2. Common Bacterial, Fungal, and Viral Infections

Meningitis

Meningitis is defined as an inflammation of the meninges that is identified by an abnormal number of white blood cells in the cerebrospinal fluid (CSF).

Causative agents

A wide variety of organisms is associated with this disease, including many Gram-positive and Gram-negative organisms.

Clinical presentation

Patients may present with fever, headache, photophobia, neck rigidity, diarrhea, vomiting, and altered mental status. Infants may present with a bulging anterior fontanel.

Diagnostic criteria

Analysis of the cerebrospinal fluid may be diagnostic of the infective agent. Bacterial agents are associated with a large increase in systemic WBCs, presence of WBCs in the CSF, increased CSF protein, and decreased CSF glucose. Fungal and viral agents exhibit smaller increases in CSF WBCs, smaller increases in CSF protein, and limited decreases in CSF glucose.

Treatment

Empiric treatment is usually determined by the age of the patient. Because of limited antibiotic penetration by many agents, the highest safe antibiotic doses are generally used.

Table 29-1 summarizes empiric therapy for meningitis.

Endocarditis

Endocarditis is an infection of the endocardium, the membrane lining the heart chamber and valves.

Causative agents

Most patients have previous damage to the heart (e.g., artificial valve placement) prior to infection. The most common organisms are Streptococcus and Staphylococcus species.

Clinical presentation

Patients present with low-grade fever, fatigue, and weakness. A diagnostic finding is the presence of splinter hemorrhages and petechiae.

Diagnostic criteria

There are no specific laboratory tests for this infection. Most patients present with an elevated erythrocyte sedimentation rate or C-reactive protein. Visualization of the vegetations on the surface of the heart is often diagnostic of the disease.

Treatment

According to American Heart Association guidelines, treatment varies depending on the causative organism and whether or not prosthetic devices are present (which would require longer therapy, if present).

Table 29-2 describes therapy for endocarditis.

Acute or Chronic Bronchitis

Bronchitis is an inflammation of the bronchioles, often associated with bronchopneumonia. Chronic bronchitis is mainly associated with heavy smoking.

Causative agents

Viral infections account for half of all cases. Mycoplasma pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Chlamydia pneumoniae are common bacterial pathogens.

Clinical presentation

Patients present with a history of acute productive cough, a low-grade fever, and a clear chest x-ray.

Diagnostic criteria

Sputum cultures typically are not useful in diagnosis because of multiple etiologies; therefore, most physicians prescribe anti-infectives on the basis of physical findings.

Treatment

Treatment is controversial for most acute illnesses because of the large percentage of viral cases. Chronic cases are treated, but bacterial resistance can easily

[Table 29-1. Empiric Treatment of Meningitis]

[Table 29-2. Therapy for Endocarditis]

develop from the use of multiple antibiotic treatments.

Table 29-3 describes treatment for acute and chronic bronchitis.

Pneumonia

Pneumonia is an inflammation of the lung parenchyma characterized by consolidation of the affected part, as well as filling of the alveolar air spaces with exudates, inflammatory cells, and fibrin. Distribution may be lobar, segmental, or lobular. If pneumonia is associated with bronchitis (see the previous discussion of bronchitis), it is termed bronchopneumonia.

Causative agents

Multiple bacterial etiologies are possible, depending on predisposing conditions (

Table 29-4).

[Table 29-3. Treatment of Acute and Chronic Bronchitis]

Clinical presentation

Typically, the onset of illness is abrupt or subacute, with fever, chills, dyspnea, and productive cough predominating. On physical examination, the patient is tachypneic and tachycardic, frequently with chest wall retractions and grunting respirations. The complete blood count usually reflects a leukocytosis with a predominance of polymorphonuclear cells.

Diagnostic criteria

Sputum culture may be useful in identifying some pathogens. However, difficulty in obtaining a deep sputum culture and problems in culturing some organisms (e.g., Legionella) make positive identification of the organism difficult.

Treatment

Treatment varies by age group.

Tuberculosis

Tuberculosis is a communicable infectious disease caused by Mycobacterium tuberculosis. It can produce silent, latent infection as well as active infection. Although infection of any tissue or organ with M. tuberculosis is possible, the usual site of infection is pulmonary.

[Table 29-4. Empiric Treatment of Pneumonia]

Clinical presentation

Tuberculosis can present with generalized symptoms of weight loss, fever, and night sweats, along with persistent cough productive of sputum. In the absence of other symptoms, latent disease is defined by a positive PPD (purified protein derivative) test.

Diagnostic criteria

Diagnosis often is made by a combination of chest x-ray (which often shows patchy or nodular infiltrates in the apical areas of the upper lobes or the superior segment of the lower lobes) and positive PPD skin test. Patients with severe HIV disease may not react to the standard PPD skin test. Sputum or lung biopsy may be acid-fast stained to reveal the organism. Because of the extended time period needed to grow the organism, sensitivities to anti-infective agents may take weeks to months to determine.

Treatment

See

Table 29-5 for a summary of treatments.

Infectious Diarrhea

Diarrhea is defined as an increase in frequency or liquidity of stool (or both) compared to a patient's normal stool.

[Table 29-5. Treatment of Tuberculosis]

Causative agents

Many disease states, drugs, and infectious organisms have been associated with diarrhea.

Clinical presentation

The patient may present with several of the following symptoms: fever, chills, nausea, vomiting, and abdominal cramping.

Diagnostic criteria

Etiology often is determined by patient history and physical examination. Because of the nature of the disease, cultures often are not diagnostic, except for determination of carrier states.

Treatment

Supportive care (hydration, antipyretics, and antiemetics) is useful. Antimotility agents are discouraged because of the potential to cause toxic megacolon. Antibacterial therapy is reserved for severe presentations or for patients with risk factors.

Table 29-6 provides an overview of treatments.

Skin and Soft Tissue Infections

Bacterial infection of the skin can be classified as direct infection of the skin (cellulitis) or secondary infection of a wound or incision.

Causative agents

Cellulitis usually is infection caused by a single organism. The most common organisms are Streptococcus pyogenes and Staphylococcus aureus. Secondary infections may be polymicrobial, including both anaerobic and aerobic organisms.

Clinical presentation

Skin and soft tissue infections are characterized by erythema and edema of the skin.

[Table 29-6. Treatment of Infectious Diarrhea]

[

Table 29-7. Treatment of Skin and Soft Tissue Infections]

Diagnostic criteria

Diagnosis is usually made from physical examination. Cultures usually are not diagnostic.

Treatment

Treatment is empiric, based on likely organisms (Table 29-7).

Urinary Tract Infections

Urinary tract infections (UTIs) represent a wide variety of clinical syndromes, including urethritis, cystitis, prostatitis, and pyelonephritis.

Causative agents

The most common agents are Gram-negative facultatively anaerobic rods (coliforms). Hospitalized, catheterized patients also may acquire Pseudomonas and Staphylococcus species.

Clinical presentation

Lower urinary tract infections tend to present with dysuria, urgency, frequency, nocturia, and suprapubic heaviness or pain. Fever is rare. Upper urinary tract infections tend to present with flank pain and fever.

Diagnostic criteria

Key to the diagnosis of UTIs is the ability to demonstrate significant numbers of organisms present in an appropriately drawn urine sample. In general, higher numbers of organisms (>105 cells/mL) are needed to diagnose UTIs in females than in males (>103 cells/mL), because more organisms are able to ascend the shorter female urethra. In addition, the presence of WBCs in the urine sample may be a significant clue for infection.

Treatment

A variety of antibacterials may be useful for the treatment of urinary tract infections (

Table 29-8), including

[Table 29-8. Treatment of Urinary Tract Infections]

fluoroquinolones, cephalosporins, trimethoprim-sulfamethoxazole (TMP-SMX), and doxycycline. Fluoroquinolones are especially useful for the treatment of prostatitis. Length of therapy varies according to the severity of disease.

Bacterial Venereal Diseases (Gonorrhea and Syphilis)

Venereal diseases are diseases that can be transmitted via sexual intercourse. This section covers only the major bacterial venereal diseases, which are gonorrhea and syphilis. Viral venereal diseases (e.g., herpes and hepatitis) will follow in this chapter or other chapters (for HIV, see Chapter 31).

Causative agents

Syphilis is caused by an infection with the spirochete Treponema pallidum, whereas gonorrhea is caused by the Gram-negative coccus Neisseria gonorrhoeae.

Clinical presentation

Primary syphilis presents as painless lesions or chancres appearing at the site of infection around 21 days after exposure. The lesions persist for about 8 weeks before disappearing spontaneously.

Secondary syphilis develops 2-6 weeks after the onset of the primary stage and is characterized by a variety of rashes and flu-like symptoms. These symptoms disappear without treatment within 4-10 weeks. Untreated patients will develop symptoms of tertiary syphilis within 2-25 years after infection. These symptoms include general paresis, nerve deafness, progressive dementia, and aortic insufficiency.

Gonorrhea, in contrast, presents as a urethritis within 2-3 days of exposure. Dysuria, urinary frequency, and purulent discharge are common. The majority of infected patients become asymptomatic without treatment within 6 months. About 15% of infected women will develop pelvic inflammatory disease, which can be an indirect cause of future infertility.

Diagnostic criteria

Because T. pallidum cannot be grown in culture, dark-field or indirect fluorescent antibody microscopic examination is used in conjunction with serologic testing for diagnosis. The most common tests used are the Venereal Disease Research Laboratory (VDRL) test and the rapid plasma reagin (RPR) test. Gonorrhea is diagnosed by Gram stain and culture of infected secretions. Alternative methods of diagnosis include enzyme immunoassay and DNA (deoxyribonucleic acid) probes. Patients testing positive for any sexually transmitted disease should be screened for the presence of other venereal diseases.

Treatment

Because of the significant both diseases can potentially cause significant morbidity in infants born to infected mothers, diagnosis and treatment of pregnant women is of concern. The two organisms differ sharply in resistance to anti-infective agents. T. pallidum is sensitive to penicillin and has not developed any significant resistance. N. gonorrhoeae has developed significant resistance not only to penicillin but also to fluoroquinolones, leaving third-generation cephalosporins as the major treatment modality (

Table 29-9). Patients diagnosed with gonorrhea should also receive therapy against chlamydia infection (usually doxycycline 100 mg bid for 7 days or azithromycin 1 g once). All sexual partners must also be treated.

[Table 29-9. Treatment of Gonorrhea and Syphilis]

Sepsis

Sepsis has been defined by the American College of Chest Physicians as the systemic inflammatory response syndrome (SIRS) produced in response to infection. SIRS has been defined as requiring two of the following criteria: temperature > 38°C or < 36°C; heart rate > 90 bpm; respiratory rate >20 breaths/min or PaCo2 <32 torr; WBC >12,000 cells/mm3 or <4,000 cells/mm3; or >10% immature (band) forms.

Causative agents

Sepsis may be caused by a variety of organisms, including Gram-negative and Gram-positive organisms, as well as fungi. Most cases occur in a hospital setting and reflect the institution's organisms and resistance patterns.

Clinical presentation

In the early phase, the patient may have fever or hypothermia, rigors, chills, tachycardia, tachypnea, hyperglycemia, and lethargy. The condition progresses to hypotension, hypoglycemia, myocardial depression, oliguria, leukopenia, and pulmonary edema, leading to multisystem organ failure.

Diagnostic criteria

In addition to physical signs and symptoms, cultures of blood, urine, and sputum may yield clues for antibacterial therapy.

Treatment

Local organisms and sensitivities will determine anti-infective therapy. Initial therapy should be broad, covering all likely organisms, until culture results are obtained. The Medical Letter suggests the following regimens for life-threatening sepsis in adults: cefotaxime, ceftriaxone, cefepime, ticarcillin-clavulanic acid, piperacillin-tazobactam, meropenem, or imipenem with an aminoglycoside (tobramycin, gentamicin, or amikacin). If Gram-positive organisms are suspected, vancomycin or linezolid may be added to the regimen.

Tick-Borne Systemic Febrile Syndromes (Lyme Disease, Rocky Mountain Spotted Fever, Ehrlichiosis, and Tularemia)

Tick-borne illnesses are similar in transmission and natural history. The organisms responsible for these infections are Rickettsia, known for their intracellular growth in host cells. As such, they cannot be grown in culture media, and serologic tests are used for diagnosis. Patients present with fever, rash, and flu-like symptoms, as well as a history of tick exposure.

Treatment

See

Table 29-10 for treatment options.

Systemic Fungal Infections

Fungal infections fall into two categories: primary (able to cause infection in both healthy and immunocompromised patients) and opportunistic (able to cause infection only in immunocompromised patients). Many fungal infections have a pulmonary focus because of the aerosol spread of mold spores. The incidence of fungal infection is rising as a result of increased use of antibacterial agents and the increase in immunocompromised patients.

Clinical presentation

Patients present with a gradual onset of general malaise, fever, and weakness, which are unrelieved by antibacterial therapy. Pulmonary infection usually presents with pneumonia-like symptoms.

[Table 29-10. Treatment of Tick-Borne Systemic Febrile Syndromes]

[

Table 29-11. Treatment of Systemic Fungal Infections]

Diagnostic criteria

Diagnosis is made from patient history; cultures (usually blood, sputum, and biopsy of lesions); and serologic tests.

Treatment

Treatment often is empiric until the organism is isolated (Table 29-11). Because of the relatively slow growth of most fungi and the lack of commercial testing against antifungal agents, patient response is used to determine resistance to therapy.

Viral Infections (Hepatitis, Influenza, and the Herpes Simplex Family)

Antiviral therapy is not curative in viral infections but decreases the level of virus so that a patient's immune system can handle the infection.

Hepatitis

Hepatitis is a general term referring to a generalized inflammation of the liver. Etiologies may be viral or chemical.

Causative agents

Five viruses (hepatitis types A-E) have been identified as causative agents for hepatitis. Syndromes may be either acute or chronic.

Clinical presentation

Patients present with a history of anorexia, nausea, fatigue, and malaise, which usually progresses to fever, right upper quadrant pain, dark urine, light-colored stools, and worsening of systemic symptoms. Some patients have no symptoms and little hepatic damage.

Diagnostic criteria

In addition to physical signs, laboratory tests are remarkable for elevations in AST (aspartate aminotransferase), ALT (alanine aminotransferase), and serum bilirubin.

Treatment

Treatment depends on the viral strain and type of presentation (

Table 29-12). Standard therapies have not been established for hepatitis A, D, or E.

Influenza

Influenza is an acute respiratory viral infection.

Causative agents

Three viruses, influenza A, B, and C, are responsible for most infections.

Clinical presentation

Patients present with sudden onset of chills, fever, severe prostration, headache, muscle aches, and a

[Table 29-12. Treatment of Hepatitis]

cough that usually is dry. The primary viral infection may be followed by secondary bacterial infections.

Diagnostic criteria

Diagnosis is from patient physical signs and symptoms.

Therapy

Therapy may be either prophylaxis or treatment and is determined by viral strain in the community (

Table 29-13). Currently, no therapies exist for influenza C infections.

Herpes simplex family (herpes, cytomegalovirus, chickenpox or shingles)

The herpes simplex family is responsible for three serious viral infections: herpes genital infections, cytomegalovirus (CMV) infections in the immunocompromised, and varicella zoster infections (chickenpox and shingles).

Causative agents

Each disease is caused by a slightly different herpes virus.

Clinical presentation

Clinical presentation varies by disease:

• Genital herpes presents with flu-like symptoms of fever, headache, malaise, and myalgias, in addition to development of painful pustular or ulcerative lesions on the external genitalia.

• CMV usually presents as retinitis, colitis, or esophagitis.

• Varicella zoster presents with flu-like symptoms with a pustular rash located on body dermatomes.

Diagnostic criteria

Diagnosis is mostly from signs and symptoms, although tissue samples may be examined for the presence of the virus using immunofluorescence.

[Table 29-13. Treatment of Influenza]

[

Table 29-14. Treatment of Herpes Virus Infections]

Treatment

Treatment depends on viral and disease state. Treatment is summarized in Table 29-14.

29-3. Key Points

• The hallmark of initial anti-infective therapy is to target the specific organisms associated with the disease.

• Conversely, after the identification of the organism causing the disease, anti-infective therapy should be narrowed to cover that specific organism.

• Therapy should reflect not only the best anti-infective agent for the organism but also aspects of the patient's condition (e.g., renal function and concurrent disease states).

• Combination anti-infective therapy should be reserved for documented clinical efficacy, therapeutic failure of monotherapy, and polymicrobial infection.

• Clinical signs of infection should be followed to determine patient response to therapy.

• Empiric therapy of meningitis is age specific, reflecting the age-specific nature of the common pathogens.

• Endocarditis therapy is specific to the organism isolated. The presence of a prosthetic valve increases the time of therapy.

• Many cases of bronchitis are viral in etiology, making routine antibiotic therapy controversial.

• Empiric pneumonia therapy reflects coverage of both age-related organisms and organisms associated with patient-specific risk factors.

• Diarrhea therapy mainly should be supportive, with careful use of anti-infectives and antimotility agents.

• Diagnosis of urinary tract infections varies by numbers of organisms found in the urine. Higher numbers (>105 cells/mL) are needed to diagnose UTIs in females than in males (>103 cells/mL) because of the higher numbers of organisms able to ascend the shorter female urethra.

• A frequently overlooked aspect of the treatment of bacterial venereal diseases is the treatment of sexual partners.

• Initial therapy of sepsis should be broad in scope, covering all likely organisms, until results of cultures are obtained.

• Because of the long doubling time of most fungi and the difficulty in obtaining sensitivity to specific antifungal agents, patient response is used to determine resistance to therapy.

• Antiviral therapy is not curative but decreases the level of virus so that a patient's immune system can handle the infection.

29-4. Questions

1.

The lowest concentration of anti-infective that prevents microbial growth is called the

A. minimum bactericidal concentration.

B. minimum bacteriostatic concentration.

C. minimum inhibitory concentration.

D. minimum inhibiting concentration.

E. minimum Schillings concentration.

 

2.

Laboratory markers of infections, such as C-reactive protein, white blood cell count, and erythrocyte sedimentation rate, may not be accurate in which patient populations?

I. Elderly patients

II. Patients with chronic obstructive pulmonary disease

III. Malnourished patients

A. I only

B. II only

C. I and III only

D. II and III only

E. I, II, and III

 

3.

The hallmark of empiric therapy is

A. coverage of the most common pathogen associated with the infection.

B. coverage of the common pathogens associated with the infection.

C. coverage of all possible pathogens associated with the infection.

D. coverage of polymicrobial pathogens associated with the infection.

E. coverage of all viral organisms associated with the infection.

 

4.

When two anti-infective therapies together produce a greater effect than the effects of each used alone, this phenomenon is termed

A. commensalism.

B. synergy.

C. antagonism.

D. additive.

E. interacting.

 

5.

Analysis of the cerebrospinal fluid may give valuable clues to the identity of the pathogen in meningitis. Given the following results, what would be indicative of a fungal infection?

I. Increase in WBCs

II. Decreased glucose

III. Increased protein

A. I only

B. II only

C. I and III only

D. II and III only

E. I, II, and III

 

6.

Empiric therapy for meningitis for patients up to 1 month of age includes

A. vancomycin and ampicillin.

B. aminoglycoside and ampicillin.

C. ceftriaxone and vancomycin.

D. vancomycin and aminoglycoside.

E. ampicillin and ceftriaxone.

 

7.

When treating penicillin-allergic patients for endocarditis, ______may be used for therapy.

A. vancomycin

B. erythromycin

C. cefazolin

D. meropenem

E. nafcillin

 

8.

Patients presenting with acute bronchitis without risk factors should be treated empirically with

A. supportive care.

B. clarithromycin.

C. cefuroxime.

D. ciprofloxacin.

E. erythromycin.

 

9.

The most common organisms associated with community-acquired pneumonia in adults are

A. Chlamydia pneumoniae, Mycoplasma pneumoniae, and Haemophilus influenzae.

B. Streptococcus pneumoniae, Haemophilus influenzae, and Chlamydia pneumoniae.

C. Mycoplasma pneumoniae, Chlamydia pneumoniae, and Streptococcus pneumoniae.

D. Mycoplasma pneumoniae, Streptococcus pneumoniae, and Haemophilus influenzae.

E. Chlamydia pneumoniae, Staphylococcus aureus, and Haemophilus influenzae.

 

10.

Empiric therapy for patients with hospital-acquired pneumonia should include

A. tobramycin and gentamicin.

B. cefotaxime and cefepime.

C. vancomycin and gentamicin.

D. gentamicin and cefepime.

E. cefepime and vancomycin.

 

11.

Treatment of latent tuberculosis infections in which isoniazid-resistant strains of Mycobacterium tuberculosis are predominant should include

A. rifabutin and pyrazinamide.

B. rifampin and pyrazinamide.

C. isoniazid, rifampin, and pyrazinamide.

D. isoniazid, rifabutin, and pyrazinamide.

E. ethambutol and rifampin.

 

12.

The use of antimotility agents in infectious diarrhea is

A. discouraged because of the potential to cause toxic megacolon.

B. encouraged because of increased cure rates.

C. discouraged because of increased reinfections.

D. encouraged because of decreased reinfections.

E. discouraged because of lack of efficacy.

 

13.

Cellulitis usually is associated with

A. Staphylococcus aureus.

B. Streptococcus bovis.

C. Peptostreptococcus boydii.

D. Escherichia coli.

E. Klebsiella pneumoniae.

 

14.

The best empiric regimen to treat prostate infection is

A. ciprofloxacin for 10 days.

B. TMP-SMX for 10 days.

C. ciprofloxacin and TMP-SMX for 10 days.

D. ciprofloxacin for 4-6 weeks.

E. TMP-SMX for 4-6 weeks.

 

15.

Tertiary syphilis in adults should be treated with

A. benzathine penicillin 2.4 million units × 1 day.

B. penicillin 50,000 units/kg q12h × 10-21 days.

C. penicillin 4 million units q4h × 10-14 days.

D. benzathine penicillin 2.4 million units q week × 3 weeks.

E. penicillin 150,000 units/kg q12h × 10-21 days.

 

16.

Candida albicans infections may be treated with

A. itraconazole.

B. amphotericin B.

C. voriconazole.

D. caspofungin.

E. ketoconazole.

 

17.

The antiviral agent with the widest spectrum of activity against influenza is

A. zanamivir.

B. rimantadine.

C. amantadine.

D. oseltamivir.

E. acyclovir.

 

18.

Herpes infections resistant to acyclovir may be treated with

A. famciclovir.

B. valacyclovir.

C. foscarnet.

D. ganciclovir.

E. high-dose acyclovir.

 

19.

In the list that follows, the only organism that can be cultured easily is

A. Treponema pallidum.

B. Mycobacterium tuberculosis.

C. Rickettsia rickettsii.

D. Ehrlichia phagocytophila.

E. Francisella tularensis.

 

20.

Anti-infective therapy always should be used to treat infectious diarrhea caused by which organism?

A. Escherichia coli

B. Vibrio cholerae

C. Staphylococcus aureus

D. Salmonella

E. Bacillus cereus

 

21.

J. B. is an 18-year-old white female who just gave birth to her first child. Because she presented without any prenatal care or history, a full prenatal panel of tests was taken, including a vaginal swab. Two days after giving birth, she complained of a purulent vaginal discharge and a low-grade fever. Blood cultures were negative, but the vaginal swab revealed the presence of Gram-negative cocci. WBCs were elevated at 13,000 cells/mm3. What is J. B.'s probable infection?

A. Herpes simplex

B. Gonorrhea

C. Syphilis

D. Urinary tract infection

E. Food poisoning

 

22.

What should be done for J. B. and her baby?

A. Both mother and child should be treated.

B. Neither mother nor child should be treated.

C. The child should be treated, but the mother should not.

D. The mother should be treated, but the child should not.

E. Mother, child, and partner should be treated.

 

23.

L. B. is a 45-year-old white female presenting to the emergency department with a fever of 103°F, flank pain, dysuria, urgency, and frequency. Her laboratory tests are significant for an increased WBC count of 18,000 cells/mm3and 3% immature forms (bands). Her urinalysis revealed >105 cells/mL of Gram-negative rods. What does L. B. have?

A. Herpes simplex

B. Gonorrhea

C. Syphilis

D. Urinary tract infection

E. Food poisoning

 

24.

What therapy would be useful for L. B.?

A. Oral quinolone

B. IV quinolone

C. Oral penicillin

D. IV carbapenem

E. IV vancomycin

 

29-5. Answers

1.

C. The minimum inhibitory concentration determines the level of anti-infective to which dosing regimens may be set.

 

2.

C. Elderly and malnourished patients may not be able to respond with appropriate laboratory markers of infections because of limited reserves or deletion of inflammatory factors.

 

3.

B. Coverage of common pathogens associated with the infection increases the probability of curing the infection without increasing anti-infective exposure to other organisms, which increases the possibility of resistance.

 

4.

B. Synergy is the correct term.

 

5.

E. Although fungal CNS infections show relatively slight changes in WBCs, protein, and glucose compared to bacterial infections, the trend is similar.

 

6.

B. This regimen covers the most likely organisms for meningitis in this age group: Gram-negative enterics (e.g., Escherichia coli), group B streptococci, and Listeria monocytogenes.

 

7.

A. Vancomycin covers all Gram-positive organisms associated with endocarditis, with no cross-sensitivity to penicillin.

 

8.

A. Because half of bronchitis infections are caused by a viral etiology, antibacterial therapy for low-risk patients should not be attempted, with the exception of severe presentation.

 

9.

D. Chlamydia pneumoniae is not a pathogen associated with adult pneumonia.

 

10.

D. Empiric therapy for hospital-acquired pneumonia should have an aminoglycoside and one other Gram-negative agent, such as cefepime. Vancomycin can be added if methicillin-resistant Staphylococcus aureus is suspected.

 

11.

B. Latent infections are usually treated with isoniazid alone. In the case of isoniazid-resistant tuberculosis, rifampin and pyrazinamide are effective at treating latent infections. The three-drug regimens are used to treat active disease.

 

12.

A. Use of such agents increases the chance of intestinal perforation and increases the length of symptoms.

 

13.

A. Most cellulitis infections are associated with Staphylococcus aureus and Streptococcus pyogenes.

 

14.

D. Prostate infections are difficult to treat, requiring 4-6 weeks of therapy. Although TMP-SMX is a reasonable choice for treating most prostate infections, ciprofloxacin is preferred because of its ability to concentrate in prostate fluid.

 

15.

C. Because of the organism load of tertiary syphilis, high doses of penicillin G are needed for clinical cure. Responses B and E are congenital syphilis doses for neonates.

 

16.

B. Voriconazole and caspofungin have activity against Candida but have not yet been tested in a variety of settings. Ketoconazole and itraconazole should not be used for serious Candida infections. Amphotericin B and fluconazole are currently recommended for Candida.

 

17.

D. Oseltamivir may be used for either treatment or prophylaxis against both influenza A and influenza B.

 

18.

C. Foscarnet has activity against acyclovir-resistant herpes.

 

19.

B. Mycobacterium tuberculosis, although very slow growing, can be grown on culture media. The remaining organisms cannot be grown without the use of cell culture techniques, forcing the clinician to rely on serum testing and direct staining for identification of the organism.

 

20.

B. Staphylococcus and Bacillus diarrheas are an intoxication not caused by a living organism. Both Salmonella and E. coli diarrheas should be treated only if severe or if signs of systemic infection are present. Vibrio cholerae causes a severe diarrhea requiring anti-infective treatment.

 

21.

B. Given the lack of prenatal care, J.B.'s physical signs and symptoms, and the presence of Gram-negative cocci, J. B. most likely has gonorrhea.

 

22.

E. Mother, partner, and child should be treated. J. B. and her partner should receive ceftriaxone 125 mg IM × 1 dose and treatment for concurrent chlamydia infection (doxycycline 100 mg bid × 7 days). The child should receive cefotaxime 25 mg/kg q12h × 7 days. Both mother and child should be screened for additional sexually transmitted diseases.

 

23.

D. Given the clinical presentation and laboratory test results, L. B. has a severe urinary tract infection. The presence of systemic symptoms (fever and chills) suggests an upper urinary tract infection or pyelonephritis.

 

24.

B. Given the severity of disease, parenteral therapy would be reasonable for initial therapy. Because the Gram stain of the urine revealed Gram-negative rods, either a quinolone or extended-spectrum penicillin in combination with an aminoglycoside would be reasonable empiric therapy until the organism is identified and sensitivities obtained.

 

29-6. References

Many general references will provide basic information concerning anti-infective therapy. The Medical Letter (www.medletter.com) publishes a good yearly review of antibacterial and antiviral therapies in brief. A list of recent practice guidelines in areas of infectious disease follows.

Meningitis

Tunkel AR, Hartman BL, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-84.

Endocarditis

Baddour LM, Wilson WR, Bayer AS, et al. Complications: A statement for healthcare professionals from the Committee Infective Endocarditis: Diagnosis, Antimicrobial Therapy, and Management of Complications. Circulation. 2005;111: e394-434.

Pneumonia

American Thoracic Society and the Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2004;171:388-416.

Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the management of community-acquired pneumonia in adults: Infectious Diseases Society of America. Clin Infect Dis. 2000;31: 347-82.

Tuberculosis

Horsburgh CR, Feldman S, Ridzon R. Practice guidelines for the treatment of tuberculosis. Clin Infect Dis. 2000;31:633-39.

Infectious diarrhea

Diagnosis and management of food-borne illnesses: A primer for physicians. MMWR Recomm Rep. 2001;50(RR-2):1-69.

Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32:331-51.

Soft tissue infections

Lipsky BA, Berendt BA, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2004;39:885-910.

Urinary tract infections

Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women: Infectious Diseases Society of America (IDSA). Clin Infect Dis. 1999;29:745-58.

Bacterial venereal diseases (gonorrhea and syphilis)

Centers for Disease Control and Prevention. Diseases characterized by genital ulcers: Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep. 2002;51(RR-6):11-25.

Centers for Disease Control and Prevention. Diseases characterized by urethritis and cervicitis. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep. 2002;51(RR-6):30-42.

Centers for Disease Control and Prevention. Vaccine preventable STDs. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep. 2002; 51(RR-6):59-64.

Sepsis

American College of Chest Physicians-Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864-74.

O'Grady NP, Barie PS, Bartlett JG, et al. Practice guidelines for evaluating new fever in critically ill adult patients. Crit Care Med. 1998;26:1042-59.

Tick-borne systemic febrile syndromes

Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme disease. Clin Infect Dis. 2000;31(suppl 1):1-14.

Systemic fungal infections

Chapman SW, Bradsher RW, Campbell GD, et al. Practice guidelines for the management of patients with blastomycosis. Clin Infect Dis. 2000; 30:679-83.

Pappas PG, Rex JH, Sobel JD, et al. Guidelines for the treatment of candidiasis. Clin Infect Dis. 2004; 38:161-89.

Saag MS, Graybill RJ, Larsen RA, et al. Practice guidelines for the management of cryptococcal disease. Clin Infect Dis. 2000;30:710-18.

Stevens DA, Kan VL, Judson MA, et al. Practice guidelines for diseases caused by Aspergillus. Clin Infect Dis. 2000;30:696-709.

Viral infections (hepatitis, influenza, and the herpes simplex family)

Association for Genitourinary Medicine, Medical Society for the Study of Venereal Disease. 2002 National Guideline for the Management of Genital Herpes. London: AGUM, MSSVD; 2002.

Association for Genitourinary Medicine, Medical Society for the Study of Venereal Disease. 2002 National Guideline on the Management of the Viral Hepatitides A, B, and C. London: AGUM, MSSVD; 2002.

Bridges CB, Fukuda K, Uyeki TM, et al. Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2002;51 (RR-03):1-31.