Pharmacokinetic-pharmacodynamic analysis of the influence of inoculum size on the selection of resistance in Escherichia coli by a quinolone in a mouse thigh bacterial infection model.Report as inadecuate




Pharmacokinetic-pharmacodynamic analysis of the influence of inoculum size on the selection of resistance in Escherichia coli by a quinolone in a mouse thigh bacterial infection model. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Physiologie et Toxicologie Expérimentales

Abstract : Maintaining quinolone concentrations outside the mutant selection window MSW between the MIC and mutant prevention concentration MPC was suggested by in vitro and in vivo studies to prevent the selection of resistant mutants. However, selection also may depend on the presence of resistant bacterial mutants at the start of treatment, which is highly dependent on the initial inoculum size. In this study, a mouse thigh bacterial infection model was used to test the influence of different exposures to marbofloxacin on the selection of resistant bacteria after infection with a low 105 CFU or high 108 CFU initial inoculum of Escherichia coli. The inoculum size was shown to influence the exposure to marbofloxacin and the values of pharmacokinetic-pharmacodynamic indices. When the abilities of the indices time within the MSW TMSW, area under the concentration-time curve of 0 to 24 h divided by the MIC, and the maximum concentration of drug in plasma divided by the MIC to predict the selection of resistant bacteria were compared, only TMSW appeared to be a good predictor of the prevention of resistance for values less than 30%. When the TMSW was higher than 34%, the selection of resistant bacteria occurred less often in thighs initially infected with the low inoculum 11-24; 46% than in those infected with the high inoculum 30-36; 80%, suggesting that the selection of resistant mutants depends on both the TMSW and inoculum size. The relevance of these results merits further investigation to test different strategies of antibiotic therapy depending on the expected bacterial burden at the infectious site.





Author: Aude A Ferran - Anne-Sylvie Kesteman - Pierre-Louis Toutain - Alain Bousquet-Mélou -

Source: https://hal.archives-ouvertes.fr/



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