Pharmacokinetics and Bacteriologic Efficacy of Moxalactam, Cefotaxime, Cefoperazone, and Rocephin in Experimental Bacterial Meningitis

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Abstract
The pharmacokinetics and bacteriologic efficacy of four β-lactam antibiotics were studied in the serum and cerebrospinal fluid (CSF) of rabbits using two test strains, Escherichia coli type Kl and group B Streptococcus type III, and 24 gram-positive isolates. Although moxalactam, cefotaxime, cefoperazone, and rocephin are active in vitro against gram-negative bacilli, the gram-positive bacteria Listeria monocytogenes and Streptococcus faecalis were resistant to all four drugs; group B streptococci were resistant to moxalactam. In rabbit CSF, moxalactam had the greatest concentration and penetration, but rocephin had the longest half-life and duration of bactericidal activity. These two drugs were most effective in the CSF of E. coli K1-infected rabbits. Except for moxalactam, the four drugs were comparable to ampicillin in reducing counts of group B Streptococcus type III in CSF. Drug accumulation in CSF and appreciable bacterial killing were observed in E. coli K1-infected animals given moxalactam either periodically or by constant infusion.