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Harrison’s Manual of Medicine



Epidemiology and Pathogenesis
Extrapulmonary Infection

The pneumococcus (Streptococcus pneumoniae) is a gram-positive encapsulated coccus that colonizes the oropharynx and causes serious illness, including pneumonia, meningitis, and otitis media.
Pneumococci colonize the oropharynx of 5–10% of healthy adults and 20–40% of children. After colonization, protection is afforded by nonspecific immune mechanisms until type-specific antibody is produced. Otitis media, a common childhood illness, develops when inflamed mucosal surfaces impede clearance of the organisms from the inner ear. Pneumococci cause 40–50% of otitis media cases in which a causative agent is identified. Any perturbation in the normal defenses of the lower respiratory tract (e.g., depressed cough, alcohol intoxication, impaired ciliary activity, viral infection) may allow infection of the lungs with pneumococci. Impaired production of specific antibody by any mechanism (e.g., multiple myeloma, HIV infection) also predisposes to infection. Once a pneumococcal infection has been initiated, the absence of a spleen predisposes to fulminant disease. Certain populations, including Native Americans and Alaskans, appear to be unusually susceptible to invasive pneumococcal disease; this increased susceptibility probably has a genetic basis. Pneumococcal pneumonia occurs at an annual rate of 20 cases per 100,000 young adults and 280 cases per 100,000 individuals >70 years of age. Epidemic pneumococcal pneumonia may occur in crowded living conditions such as prisons or military barracks but does not generally occur in schools or workplaces. Of all cases of pneumococcal pneumonia, ~25% result in bacteremia. Bacteremia, with or without pneumonia, leads to pneumococcal infection at other sites, such as the joints, the meninges, or the cardiac valves.
Pts frequently present with a preexisting respiratory illness that has worsened. Often the temperature rises to 38.9–39.4°C (102–103°F) and sputum production becomes prominent. The “classic” presentation with coryza, followed by the abrupt onset of a shaking chill and fever and cough productive of blood-tinged sputum, is not common. In the elderly the onset may be insidious. On physical exam, pts usually appear ill and anxious. Dullness to percussion is frequently found, and tubular breath sounds and fine crepitant rales may be heard. Without treatment, high fever and cough persist for 7–10 d, with subsequent defervescence. Most pts defervesce within 12–36 h of the initiation of therapy, but some take up to 4 d. The physical exam yields normal findings within 2–4 weeks, but the CXR may remain abnormal for 8–18 weeks. Pleural effusions, which are found in up to 50% of cases, are usually sterile, but empyema may occur in 2% of treated cases. Empyema can cause extensive pleural scarring if the fluid is not drained. Other complications include abdominal distention, herpes labialis, and abnormal LFTs or frank jaundice. Rarely, pts develop pericarditis, arthritis (esp. in children), endocarditis (see below), and paralytic ileus.
Gram’s stain of sputum shows large numbers of PMNs and slightly elongated gram-positive cocci in pairs and chains. Culture is less sensitive than Gram’s stain. Blood cultures are positive in ~25% of pts. The WBC count is usually >12,000/µL but may be low in overwhelming infection. In pts with asplenia or multiple myeloma and rarely in immunocompetent hosts, pneumococci may be seen in Wright’s-stained buffy coat. CXR shows homogeneous density in an involved lobe or segment in one-fourth of cases, but abnormalities may be multilobar or atypical, especially with underlying pulmonary disease.
MENINGITIS   The pneumococcus is the leading cause of bacterial meningitis in adults (except during outbreaks due to the meningococcus). Because of the success of the Haemophilus influenzae vaccine, the pneumococcus is now the leading cause in children (except for neonates) as well. Pneumococcal meningitis may present as a primary disease; as a complication of pneumonia; by extension from otitis, mastoiditis, or sinusitis; or subsequent to a skull fracture with CSF leak. The CSF is a secondary site of infection in pneumococcal endocarditis. Pts present with sudden onset of fever, headache, and stiff neck, with progression to obtundation over 24–48 h in the absence of treatment. Physical exam reveals an acutely ill pt with nuchal rigidity. LP should be performed immediately except in cases with papilledema or focal neurologic findings. If LP is deferred for any reason, treatment should be started immediately. CSF findings include increased pressure, cloudiness, pleocytosis with a predominance of PMNs, increased protein level, and decreased glucose level. The Gram’s stain is usually positive for bacteria. Although these methods have fallen out of favor, latex agglutination or counterimmunoelectrophoresis is positive in 80% of culture-positive cases and may be positive when culture is negative (e.g., in the presence of antibiotics). With appropriate therapy, 70% of pts recover.
ENDOCARDITIS   Endocarditis is a rare complication of pneumococcal pneumonia. The clinical picture is one of acute bacterial endocarditis with fever, splenomegaly, loud murmurs, metastatic infections, and rapid destruction of previously normal heart valves (particularly the aortic valve), sometimes with the development of CHF. Blood cultures are uniformly positive in the absence of antibiotics.
PERITONITIS   Pneumococcal peritonitis is a rare complication of transient pneumococcal bacteremia. Infection via the vagina and fallopian tubes may account for an increased incidence among adolescent girls and among women using intrauterine devices. The disease is also associated with cirrhosis, carcinoma of the liver, and nephrotic syndrome. Diagnosis is based on an elevated cell count and a positive culture of ascitic fluid. Blood cultures are often positive.

In the past, pneumococcal infection was uniformly susceptible to penicillin. During the past several years, however, resistance to penicillin as well as to many other antibiotics has emerged; by 1997 in the U.S., ~20% of isolates were intermediately susceptible to penicillin and 15% were resistant. Susceptibility testing should thus be routinely performed on all pneumococcal isolates, and empirical treatment should be guided by local patterns of susceptibility and the type of infection being treated. Susceptibility of a pneumococcal isolate varies with the site infected due to pharmacokinetic considerations.
Pneumonia Pts with pneumococcal pneumonia may be treated as outpatients if they are at low risk (as determined by PORT score, according to the criteria described by the Pneumonia Outcomes Research Team, HPIM- 15, Chap. 255). However, if the physician is in doubt about the severity of illness, the social circumstances, or the likelihood of compliance with the prescribed antibiotic regimen, it may be best to hospitalize the pt, at least briefly.
For outpatient treatment, amoxicillin (500 mg PO q6h) is effective in all cases except those caused by the most highly penicillin-resistant isolates. One of the newer fluoroquinolones in an accepted dosage for pneumonia is likely to be highly effective (e.g., levofloxacin, 500 mg PO qd). Clindamycin (300 mg PO q8h) is active against >90% of strains that are susceptible or intermediately susceptible to penicillin. Doxycycline, azithromycin, or clarithromycin will be effective in 85–90% of cases. For inpatient therapy, an empirical regimen active against resistant pneumococci should be considered. This regimen can consist of cefotaxime (1–2 g IV q6–8h), ceftriaxone (1–2 g IV qd), or ampicillin (1–2 g IV q6h). A quinolone or azithromycin can be given parenterally or orally (with resistance at 10–15% and 1–2%, respectively). Vancomycin (1 g IV q12h) is uniformly effective against pneumococci and should be used as initial therapy if there is reason to suspect infection with a strain resistant to the drugs listed above. The optimal duration of therapy has not been established by controlled trial, but 3–5 days of observed therapy with IV antibiotics followed by oral antibiotics for a total duration of 5 afebrile days appears reasonable.
All pleural effusions should be aspirated for diagnosis and as a guide to therapy. Drainage by chest tube is indicated if pleural fluid has a pH of <7.1, contains frank pus, or contains bacteria visible on Gram’s stain. Complete drainage should be confirmed by CT. Empyema complicates ~2% of pneumonia cases.
Meningitis Because this pneumococcal infection is the most life-threatening, empirical therapy should include vancomycin (1 g IV q12h) and a third-generation cephalosporin—either ceftriaxone (1–2 g IV q12h) or cefotaxime (2 g IV q6h)—pending the availability of susceptibility data. For isolates shown to be penicillin susceptible, treatment may continue with penicillin (4 million units IV q4h). For isolates with intermediate susceptibility to penicillin but susceptibility to the third-generation cephalosporins, vancomycin may be discontinued. The total duration of therapy is 10–14 days. The use of adjunctive glucocorticoids remains controversial. Pts with pneumococcal meningitis should be cared for initially in an ICU.
Endocarditis Treatment with vancomycin (1 g IV q12h) should be begun pending susceptibility information. Treatment may continue with a b- lactam antibiotic should the isolate prove susceptible. Pts with pneumococcal endocarditis should be cared for initially in an ICU. Surgical intervention may be mandated by valvular injury or myocardial abscess.

The 23-valent pneumococcal vaccine (0.5 mL IM) should be given to all persons >65 years of age; those with cardiac, pulmonary, hepatic, or renal disease; those with diabetes, malignancy, asplenia, CSF leak, or HIV infection; and those >2 years of age with sickle cell disease. Revaccination is recommended after 5 years (esp. in persons over age 65 and in splenectomized pts).
A multivalent pneumococcal polysaccharide-protein conjugate vaccine was licensed in February 2000 for use in children.

For a more detailed discussion, see Musher DM: Pneumococcal Infections, Chap. 138, p. 882, in HPIM-15.


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