In vitro susceptibility of Streptococcus pneumoniae strains to nine beta-lactam antibiotics and the killing kinetics of cephalosporins alone and in combination with vancomycin or gentamicin.

Minimum inhibitory concentrations (MICs) of a total of 68 Streptococcus (S.) pneumoniae strains (21 susceptible, 23 intermediate, and 24 resistant to penicillin) were tested for 9 beta-lactam antibiotics such as penicillin, cefpirome, cefotaxime, ceftriaxone, cefuroxime, ceftazidime, cefpodoxime, cefodizime, and amoxycillin. MICs to penicillin, cefotaxime, cefpirome, and ceftriaxone were also tested on Muller-Hinton blood agar supplemented with 50% human serum. Killing kinetics of 0.5, 2, and 4 times the MIC of cefpirome and cefotaxime and synergistic bactericidal activity of combinations of cephalosporins with vancomycin or gentamicin were investigated. The synergism studies were conducted with drug concentrations half of the MICs. On the basis of MIC50 values cefpirome, cefotaxime, ceftriaxone, and cefpodoxime were 8, 4, 2, and 2 times more active than penicillin, while on the basis of MIC90 values they were 8, 8, 4, and 2 times superior to penicillin for the penicillin-resistant S. pneumoniae. Cefuroxime, cefodizime, and amoxycillin showed an identical or a 2-fold higher MIC50 or MIC90 than penicillin for the same group of isolates. Ceftazidime showed the lowest activity against S. pneumoniae. MIC50 and MIC90 values for ceftriaxone increased 4-fold when human serum was added to the test medium. Cefpirome was the only drug with MIC50 for the penicillin-resistant S. pneumoniae below the new resistance breakpoint of the NCCLS (> or = 2 mg/liter), while these values for cefotaxime and ceftriaxone were identical to or 2-fold higher than the resistance breakpoint. The MIC50 and MIC90 of the other drugs tested exceeded the breakpoint 2 to 16 times. The combination of vancomycin with cefpirome or cefotaxime showed a higher killing activity to two penicillin-resistant strains tested than 2- and 4-fold concentrations of the MICs of the two cephalosporins alone.