Efficacy of Cefotaxime and Latamoxef for Escherichia coli Bacteremia and Meningitis in Newborn Rats

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Abstract
We have evaluated the efficacy of cefotaxime and latamoxef against a Kl Escherichia coli strain in vitro and in vivo. In vitro, the minimal inhibitory concentrations (MICs) were close to the minimal bactericidal concentrations (MBCs) for both antibiotics (≤2dilutions). However, with an inoculum of 107 CFU/ml, MIC and MBC were significantly greater than those with inocula of 103 and 105. In vivo study with an infant rat model of bacteremia and meningitis revealed that (1) both cefotaxime and latamoxef penetrated well into the cerebrospinal fluid (CSF), (2) both drugs were bactericidal in blood and CSF, (3) both were effective in prevention of the development of meningitis in bacteremic animals, and (4) the mortality rates were significantly less in the treated than in the control group (p < 0.001). However, even with cefotaxime or latamoxef treatment, the mortality was significantly greater (p < 0.001) in rats whose bacterial counts before therapy were ≥106 CFU/ml of blood. These findings suggest that the effects of cefotaxime and latamoxef may be directly correlated with the size of the bacterial population exposed to these agents and that this variable may be an important factor to influence the therapeutic outcome.