Pharmacokinetics and bacteriological effect of ceftazidime in experimental Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli meningitis

The pharmacokinetics and bacteriological effect of ceftazidime were evaluated in rabbits experimentally infected with Streptococcus pneumoniae, Haemophilus influenzae type b, and Escherichia coli K1. The mean penetration of ceftazidime into cerebrospinal fluid after single-dose or constant-infusion administration ranged from 7.8 to 14.9%. The median cerebrospinal fluid bactericidal titers were 1:64 against S. pneumoniae and H. influenzae and 1:128 against E. coli. The bacterial colony counts in cerebrospinal fluid were reduced by 58% to 100% (-2.3 to -3.9 log10 CFU/ml) in 3 h and by 100% (-3.2 to -5.1 log10 CFU/ml) in 9 h of constant infusion, whereas in untreated infected animals, bacterial counts increased from +1.4 to +2.1 log10 CFU/ml in 9 h. These data on ceftazidime compare favorably with those on penicillin, chloramphenicol, netilmicin, and moxalactam in this experimental meningitis model.