Pharmacokinetics and therapeutic efficacy of imipenem, ceftazidime, and ceftriaxone in experimental meningitis due to an ampicillin- and chloramphenicol-resistant strain of Haemophilus influenzae type b.

The pharmacokinetics and therapeutic efficacy of imipenem, ceftazidime, and ceftriaxone were compared with those of ampicillin and chloramphenicol in rabbits with experimental meningitis due to an ampicillin- and chloramphenicol-resistant strain of Haemophilus influenzae type b. The mean bacterial colony counts in cerebrospinal fluid were reduced by 49% (-1.85 log10 CFU/ml), 92% (-3.37 log10 CFU/ml), and 92% (-4.30 log10 CFU/ml) after a single dose of imipenem, ceftazidime, and ceftriaxone, respectively. The median peak cerebrospinal fluid bactericidal titers against this multiply resistant strain of H. influenzae were 1:4 for thienamycin, 1:16 for ceftazidime, and 1:256 for ceftriaxone. By contrast, no bactericidal activity was observed in cerebrospinal fluid and the mean concentrations of H. influenzae were either unchanged or slightly increased in animals treated with ampicillin or chloramphenicol.