Efficacy of Cefotaxime and Latamoxef for <i>Escherichia coli </i>Bacteremia and Meningitis in Newborn Rats

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.

Efficacy of cefmenoxime in experimental Escherichia coli bacteremia and meningitis

“…The overall mortality in recipients of cefmenoxime was not significantly different from that of recipients of cefotaxime or ampicillin (Table 3). It has been shown previously that the in vitro and in vivo effects of cefotaxime are dependent on the size of bacterial populations (6). This inoculum effect for cefotaxime was again confirmed in this experiment (Table 3).…”

“…d Drug levels were derived from results of previous experiments (6). e Drug levels were derived from results of previous experiments (5).…”

“…It has been shown previously that experimental Escherichia coli bacteremia and meningitis induced in the newborn rat is suitable for evaluating in vivo efficacies of various antimicrobial agents, particular in terms of rates of bacterial clearance from blood and cerebrospinal fluid (CSF) and of mortality (4)(5)(6). In these studies, it has been shown the activity of armpicillin against E. coli Kl is limited (4,5), but that of cefotaxime is excellent.…”

The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat.

“…Briefly, outbred, pathogen-free, pregnant Sprague-Dawley rats with timed conception were purchased from Charles River Breeding Laboratories (Wilmington, MA); the rats delivered in our vivarium 5-7 d after arrival. Each adult rat and her pups (average litter size of 10 with range of [8][9][10][11][12][13][14][15][16] for the unencapsulated mutant and 5.0 x 106 to 1.0 X I0' CFU for the rough mutants (strains XYL and 2513). 24 h after inoculation, blood and CSF specimens were obtained as described previously (4,(12)(13)(14)(15)(16)(17) for quantitative cultures.…”

“…Hematogenous infection of meninges can be reliably established without the need for administration ofadjuvant or direct inoculation ofbacteria into CSF (4,(12)(13)(14)(15)(16)(17). With development of techniques for atraumatic collection of blood and CSF specimens, we have used this model to determine whether or not the K1 capsule and/or 0-LPS antigen are critical determinants in the development of E. coli meningitis.…”