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JAC Advance Access published online on February 21, 2006

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl041
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received September 29, 2005
Revised January 25, 2006
Accepted January 30, 2006

Original article

Urine bactericidal activity against resistant Escherichia coli in an in vitro pharmacodynamic model simulating urine concentrations obtained after 2000/125 mg sustained-release co-amoxiclav and 400 mg norfloxacin administration

Luis Alou 1, Lorenzo Aguilar 1, David Sevillano 1, María-José Giménez 1, Fabio Cafini 1, Eva Valero 1, María-Teresa Relaño 1, and José Prieto 1 *

1 Microbiology Department, School of Medicine, Universidad Complutense, Avda. Complutense s/n, 28040 Madrid, Spain

* To whom correspondence should be addressed.
José Prieto, E-mail: jprieto{at}med.ucm.es


   Abstract

Objectives: To explore the urine bactericidal activity of co-amoxiclav and norfloxacin against Escherichia coli in an in vitro pharmacodynamic model simulating the human urinary concentrations observed after administration of a single oral dose of 2000/125 mg sustained-release co-amoxiclav and 400 mg norfloxacin.

Methods: Six E. coli isolates exhibiting amoxicillin/clavulanic acid MICs of 4/2 (two strains), 8/4, 16/8, 32/16 and 64/32 mg/L and norfloxacin MICs of ≤0.25 mg/L (three strains), 32, 64 and 256 mg/L were used. Colony counts were determined over 12 h and differences between the bacterial counts of initial inocula and the bacterial counts at each sampling time-point were calculated.

Results: With co-amoxiclav, bactericidal activity (>3 log10 reduction) was obtained against the susceptible (MIC ≤ 8/4 mg/L) and intermediate (MIC = 16/8 mg/L) strains from 3 to 12 h, and from 3 to 10 h against the resistant strains (MIC ≥ 32/16 mg/L), which exhibited a 2 log10 reduction at 12 h. With norfloxacin, bactericidal activity was obtained against the susceptible strains from 4 to 12 h and from 8 to 12 h against the resistant strain with an MIC of 32 mg/L. Regrowth, with respect to initial inocula, occurred from 8 h onwards with the strain with MIC = 64 mg/L and from 3 h onwards with the strain with MIC = 256 mg/L.

Conclusions: While regrowth occurs after exposure of high norfloxacin-resistant E. coli to urine physiological concentrations of norfloxacin, this study suggests that clavulanic acid can be given twice daily (to protect amoxicillin activity) with respect to uncomplicated cystitis due to E. coli exhibiting amoxicillin/clavulanic acid MICs up to 64/32 mg/L.

Keywords: pharmacodynamic modelling; E. coli; urine bactericidal activity; amoxicillin; clavulanic acid.
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D. Sevillano, L. Aguilar, L. Alou, M.-J. Gimenez, M. Torrico, N. Gonzalez, F. Cafini, M.-T. Relano, P. Coronel, and J. Prieto
Urine Bactericidal Activity against Escherichia coli Isolates Exhibiting Different Resistance Phenotypes/Genotypes in an In Vitro Pharmacodynamic Model Simulating Urine Concentrations Obtained after Oral Administration of a 400-Milligram Single Dose of Cefditoren-Pivoxil
Antimicrob. Agents Chemother., March 1, 2008; 52(3): 1184 - 1186.
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