Prediction of in-vivo efficacy by in-vitro early bactericidal activity with oral beta-lactams, in a dose-ranging immunocompetent mouse sepsis model, using strains of Streptococcus pneumoniae with decreasing susceptibilities to penicillin

Journal of Chemotherapy
E Pérez-TralleroL Aguilar

Abstract

Killing curves and a sepsis model were performed with Streptococcus pneumoniae strains (MICs of penicillin = 0.01, 1, 2 and 4 mg/L) to assess the in vivo effect of in vitro early bactericidal activity. Optimal bactericidal concentration (OBC) was defined as the minimal concentration needed to obtain the maximal bactericidal activity during the sampling time for colony counting in killing curves. Animals were treated with amoxycillin, cefuroxime or cefpodoxime every 8 h for 48 h, with doses ranging from 2.5 to 50 mg/kg. ED100 (minimal antibiotic dose obtaining a 100% survival) was used as efficacy endpoint. Cmax/MIC, AUC/MIC and deltaT >MIC did not accurately predict efficacy against the most resistant strains, deltaT >OBC being the most predictive efficacy parameter indicating the in vivo effect of early bactericidal activity. Lower deltaT >OBC values for amoxycilin vs oral cehalosporins were needed for efficacy. The higher early bactericidal activity of amoxycillin may explain its higher in vivo efficacy.

References

Sep 1, 1992·The Journal of Antimicrobial Chemotherapy·J LiñaresR Martín
Jul 1, 1990·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·A Dalhoff, U Ullmann
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Jan 1, 1981·Reviews of Infectious Diseases·H Mattie
Aug 1, 1998·The Journal of Antimicrobial Chemotherapy·E Pérez-TralleroM Gomariz

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Citations

Nov 25, 2004·Antimicrobial Agents and Chemotherapy·Marco R OggioniGianni Pozzi

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