In vitro killing of penicillin-susceptible, -intermediate, and -resistant strains of Streptococcus pneumoniae by cefotaxime, ceftriaxone, and ceftizoxime: a comparison of bactericidal and inhibitory activity with achievable CSF levels.

This study assessed total microbial killing of 30 penicillin-susceptible, -intermediate, and -resistant strains of Streptococcus pneumoniae by cefotaxime, ceftriaxone, and ceftizoxime and compared these values with MICs for each strain against each agent as determined by three different methods/media. The results confirm the appropriateness of recent NCCLS recommendations for MIC interpretive criteria for third generation cephalosporins in which < or = 0.25 microgram/ml = susceptible and > or = 2.0 micrograms/ml = resistant when these agents are used to treat pneumococcal meningitis and data from total microbial killing studies suggests that most isolates with MICs of 0.5 and 1.0 mcg/ml would respond to high dose therapy with all three agents. The study also confirmed the recently described two- to four-fold decrease in activity of ceftizoxime against S. pneumoniae as compared with either cefotaxime or ceftriaxone; but noted that current NCCLS MIC interpretive criteria for the therapy of meningitis remain valid for all three agents. Finally, the study found that MICs determined by the E test or by microdilution broth methods using supplemented Todd Hewitt broth predict susceptibility as well as the NCCLS reference method. The actual selection among these agents for the therapy of pneumococcal meningitis should also consider other parameters including protein binding, age groups of clinical use, maximum potency against all clinically relevant pathogens, and cost.