Treatment of Pneumococcal Meningitis
Sources: American Academy of Pediatrics. Committee on Infectious Diseases. Pediatrics 1997;99:289-299; Quagliarello VJ, Scheld WM. N Engl J Med 1997;336:708-717.
The committee on infectious diseases of the American Academy of Pediatrics has published recommendations for the treatment of children with serious infection caused by Streptococcus pneumoniae. Only the recommendations relative to the treatment of meningitis will be summarized here. The recommendations of Quagliarello and Scheld are similar but less detailed. It should be noted that, while the drug dosages and information about concomitant corticosteroid therapy differ with regard to the treatment of adults, the basic principles outlined apply to this group as well.
The need for new recommendations for treatment of these infections is the result of the increasing antimicrobial resistance of the pneumococcus. In 1994, isolates from 25% of patients with invasive pneumococcal disease in Atlanta were nonsusceptible to penicillin, with 7% being fully resistant; 9% were nonsusceptible to cefotaxime, with 4% being fully resistant (Hoffmann J, et al. N Engl J Med 1995;333:481-486). Resistance to vancomycin has not yet been reported.
The use of terminology such as "nonsusceptible" is based on current recommendations. Nonsusceptible isolates include both those with intermediate susceptibility and those that are resistant. Pneumococci with an MIC less than 0.06 mcg/mL to penicillin are considered susceptible, while those with an MIC greater than 0.1 mcg/mL are considered nonsusceptible. Among the nonsusceptible, those whose MIC is 0.1-1.0 mcg/mL are intermediate, while those with an MIC greater than 2 mcg/mL are resistant. The comparable MICs for ceftriaxone are less than 0.5 (susceptible), 1 (nonsusceptible-intermediate), and greater than 2 mcg/mL (nonsusceptible-resistant).
Children with pneumococcal meningitis (or possible pneumococcal meningitis) should initially receive vancomycin plus either cefotaxime or ceftriaxone. For those with a history of significant immediate allergic hypersensitivity to beta-lactam antibiotics, consideration should be given to administration of vancomycin plus rifampin. If the pneumococcal isolate proves to be susceptible to penicillin, the child should be treated with penicillin alone or with continuation of the cephalosporin. If the isolate is nonsusceptible to penicillin, but susceptible to cefotaxime or ceftriaxone, vancomycin should be discontinued and the cephalosporin continued. Finally, if the isolate is nonsusceptible to penicillin and to cefotaxime or ceftriaxone, the cephalosporin should be discontinued, and rifampin should be added to the vancomycin if the organism is susceptible to rifampin.
The addition of rifampin to the regimen or its substitution for vancomycin should be considered if: 1) the organism is susceptible to rifampin and the clinical status has worsened after 24-48 hours despite administration of vancomycin plus ceftriaxone or cefotaxime; 2) there is no evidence of bacteriologic improvement on CSF obtained at that time; or 3) the isolate has an MIC greater than 4 mcg/mL to the cephalosporin.
The effectiveness of adjunctive corticosteroid therapy in children (or adults) with pneumococcal meningitis remains unproven. If dexamethasone is given, it should be started shortly before or at the time of initiation of antibiotic therapy. While animal models suggest that dexamethasone administration may diminish the penetration of both vancomycin and ceftriaxone into the CSF, observations in children suggest that this is not important (Gaillard JL, et al. Antimicrob Agents Chemother 1994;38:1209-1210). Patients given dexamethasone should be considered candidates for repeat lumbar puncture after 24-48 hours of therapy, as should those with lack of clinical improvement.
The antibiotic recommendations of Quagliarello and Scheld are similar to those of the committee. They recommend that antibiotic therapy be continued for 10-14 days. These recommendations can only be considered tentative, given the dynamic situation with regard to evolving antimicrobial resistance patterns among the pneumococci. What will happen when these organisms become resistant to vancomycin?
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