Chapter 128. Pneumococcal Infections (Part 9) Inpatient Therapy Pneumococcal pneumonia is readily treatable with β-lactam antibiotics. The conventional dosages shown in Table 128-5 are acceptable against intermediately resistant strains and against many or most fully resistant isolates. Recommended agents include ceftriaxone and cefotaxime. Ampicillin is also widely used, usually in the form of ampicillin/sulbactam. The likely efficacy of newer quinolones such as moxifloxacin, macrolides such as azithromycin, and clindamycin is discussed above. On the basis of in vitro considerations, vancomycin is likely to be uniformly effective against pneumococci; this drug or a quinolone should be used together with a third-generation cephalosporin for initial therapy in a patient who is likely to be infected with a highly antibiotic-resistant strain. Patients who have had a severe allergic reaction to penicillins or cephalosporins may be treated with a carbapenem (e.g., imipenem-cilastatin), a quinolone, or vancomycin. The failure of a patient to respond promptly should at least prompt consideration of drug resistance. Evidence for loculated infections (such as empyema) and/or other causes of fever should be sought and addressed appropriately. Duration of Therapy The optimal duration of treatment for pneumococcal pneumonia is uncertain. Pneumococci begin to disappear from the sputum within several hours after the first dose of an effective antibiotic, and a single dose of procaine penicillin, which produces an effective antimicrobial level for 24 h, was curative in otherwise-healthy young adults in an era when all isolates were susceptible. Early in the antibiotic era, most physicians treated pneumococcal pneumonia for 5–7 days. In the absence of data suggesting a need for longer treatment, younger physicians tend to treat the infection for 10–14 days. In the opinion of this author, a few days of close observation and parenteral therapy followed by an oral antibiotic—with the entire course of treatment continuing for no more than 5 days after the patient becomes afebrile—may be the best approach for treating pneumococcal pneumonia, even in the presence of bacteremia. Cases with a second focus of infection (e.g., empyema or septic arthritis) require longer therapy. Meningitis (Table 128-6) Pneumococcal meningitis should be treated initially with ceftriaxone plus vancomycin. Equivalent doses of cefotaxime or cefepime may be used in place of ceftriaxone. The cephalosporin will be effective against most— but not all—isolates and will readily penetrate the blood-brain barrier; all isolates will be susceptible to vancomycin, but this drug has a somewhat unpredictable capacity to cross the blood-brain barrier. If the isolate is shown to be susceptible or intermediately resistant, treatment can be continued with ceftriaxone, and vancomycin can be discontinued. If the organism is resistant, treatment with both drugs should be continued. A very few studies of experimental animals suggest benefits of the addition of rifampin, but in vitro studies indicate antagonism between this drug and ceftriaxone or vancomycin; in the absence of data to support the practice in humans, this author does not recommend that rifampin be added. Imipenem may be used in place of the cephalosporin in patients who have had life-threatening allergic reactions to β-lactam antibiotics. The total duration of therapy for pneumococcal meningitis is 10 days. A recent study demonstrated clear benefit from the addition of glucocorticoids (Chap. 376). Table 128-6 Treatment of Pneumococcal Meningitis Circumstance Appropriate Course a Diagnosis of pneumococcal meningitis; Treat with ceftriaxone, 2 g q12h, plus vancomycin, 500 mg q6h, until antibiotic antibiotic susceptibility unknown susceptibility of organism is known. Susceptibility results available Continue treat ment with ceftriaxone alone if organism is susceptible or intermediate; continue both ceftriaxone and vancomycin if organism is resistant. Life- threatening penicillin allergy Treat with imipenem, 500 mg q6h, rather than a β-lactam antibiotic. a Treatment should be administered for 5– 7 days after defervescence or for a total of 10 days. Endocarditis Pneumococcal endocarditis is associated with rapid destruction of heart valves. Pending results of susceptibility studies, treatment should be initiated with ceftriaxone or cefotaxime; if the prevalence of highly resistant strains increases, it might be prudent to add vancomycin until results of susceptibility studies are available. In vitro, aminoglycosides are somewhat synergistic and rifampin or quinolones are antagonistic with β-lactams against pneumococci; there is no clear evidence from in vivo studies that adding any of these antibiotics to the regimen is beneficial. Other Therapeutic Modalities Addition of drotrecogin, an activated protein C preparation, may be beneficial in treating patients with severe pneumococcal sepsis. Glucocorticoids and agents that block the action of TNF-α, IL-1, or platelet-activating factor have conferred no benefit. . Chapter 128. Pneumococcal Infections (Part 9) Inpatient Therapy Pneumococcal pneumonia is readily treatable with β-lactam antibiotics. The conventional dosages shown in Table 128- 5. pneumococcal pneumonia, even in the presence of bacteremia. Cases with a second focus of infection (e.g., empyema or septic arthritis) require longer therapy. Meningitis (Table 128- 6) Pneumococcal. duration of therapy for pneumococcal meningitis is 10 days. A recent study demonstrated clear benefit from the addition of glucocorticoids (Chap. 376). Table 128- 6 Treatment of Pneumococcal Meningitis