Bactericidal activity of cefotaxime, desacetylcefotaxime, rifampin, and various combinations tested at cerebrospinal fluid levels against penicillin-resistant Streptococcus pneumoniae

Penicillin resistance is increasingly prevalent amongst clinical isolates of Streptococcus pneumoniae. Recently, isolates resistant to the extended-spectrum cephalosporins have also begun to emerge, and combination therapy may be necessary for infection with such organisms. We have studied the activity of cefotaxime, ceftriaxone, ceftazidime, rifampin, chloramphenicol, and vancomycin against 10 S. pneumoniae strains with penicillin minimum inhibitory concentrations (MICs) ranging from 0.03-8 μg/ml. The bactericidal activity of cefotaxime, desacetylcefotaxime, rifampin, and combinations of these agents (cerebrospinal fluid levels) against these isolates was determined. Elevated MICs to penicillin were associated with generally twofold lower cefotaxime MICs. All strains remained susceptible to vancomycin and rifampin. The bactericidal activity of cefotaxime with or without desacetylcefotaxime was reduced by the addition of rifampin. Pneumococcal isolates with penicillin MICs of ≤1 μg/ml were slowly killed by cefotaxime alone or with desacetycefotaxime. At present, there is little evidence to support the addition of rifampin to cefotaxime for therapy of meningitis.