IN-VITRO KILLING OF PENICILLIN-SUSCEPTIBLE, PENICILLIN-INTERMEDIATE, AND PENICILLIN-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-susceptib le, -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 di fferent methods/media. The results confirm the appropriateness of rece nt NCCLS recommendations for MIC interpretive criteria for third gener ation cephalosporins in which less than or equal to 0.25 mu g/ml = sus ceptible and greater than or equal to 2.0 mu g/ml = resistant when the se agents are used to treat pneumococcal meningitis and data from tota l 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 ag ents. The study also confirmed the recently described two- to four-fol d decrease in activity of ceftizoxime against S. pneumoniae as compare d with either cefotaxime or ceftriaxone; but noted that current NCCLS MIC interpretive criteria for the therapy of meningitis remain valid f or all three agents. Finally, the study found that MICs determined by the E test or by microdilution broth methods using supplemented Todd H ewitt broth predict susceptibility as well as the NCCLS reference meth od. The actual selection among these agents for the therapy of pneumoc occal meningitis should also consider other parameters including prote in binding, age groups of clinical use, maximum potency against all cl inically relevant pathogens, and cost.