Document Detail

Ex vivo pharmacodynamics of amoxicillin-clavulanate against beta-lactamase-producing Escherichia coli in a yucatan miniature pig model that mimics human pharmacokinetics.
MedLine Citation:
PMID:  12435677     Owner:  NLM     Status:  MEDLINE    
The objective of the present study was to investigate the potential bactericidal activity of amoxicillin-clavulanate against beta-lactamase-producing Escherichia coli strains and to elucidate the extent to which enzyme production affects the activity. Six adult Yucatan miniature pigs received a single intravenous dose of 1.1 g of amoxicillin-clavulanate as an intravenous infusion over 30 min. The pharmacokinetic parameters were determined for the serum samples and compared to the published data for humans (2.2-g intravenous dose). The parameters were comparable for the two species, and therefore, the miniature pig constitutes a good model for pharmacodynamic study of amoxicillin-clavulanate. Therefore, the model was used in an ex vivo pharmacodynamic study of amoxicillin-clavulanate against four strains of Escherichia coli producing beta-lactamases at different levels. The E. coli strains were cultured with serial dilutions (1:2 to 1:256) of the serum samples from the pharmacokinetic study, and the number of surviving bacteria was determined after 1, 3, and 6 h of exposure. Amoxicillin-clavulanate at concentrations less than the MIC and the minimal bactericidal concentration had marked bactericidal potency against the strain that produced low levels of penicillinase. For high-level or intermediate-level beta-lactamase-producing strains, the existence of a clavulanate concentration threshold of 1.5 to 2 micro g/ml, below which there was no bactericidal activity, was demonstrated. The index of surviving bacteria showed the existence of mixed concentration- and time-dependent actions of amoxicillin (in the presence of clavulanate) which varied as a function of the magnitude of beta-lactamase production by the test strains. This study shows the effectiveness of amoxicillin-clavulanate against low- and intermediate-level penicillinase-producing strains of E. coli. These findings are to be confirmed in a miniature pig experimental infection model.
Stéphane Bronner; Valérie Murbach; Jean-Daniel Peter; Dominique Levêque; Hassan Elkhaïli; Yves Salmon; Nathalie Dhoyen; Henri Monteil; Gary Woodnutt; François Jehl
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  46     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-18     Completed Date:  2003-05-01     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3782-9     Citation Subset:  IM    
Laboratoire d'Antibiologie, Institut de Bactériologie, Université Louis Pasteur, Hôpitaux Universitaires de Strasbourg, France.
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MeSH Terms
Amoxicillin-Potassium Clavulanate Combination / blood,  pharmacokinetics,  pharmacology*
Area Under Curve
Escherichia coli / drug effects*,  metabolism
Infusions, Intravenous
Metabolic Clearance Rate
Microbial Sensitivity Tests
Models, Biological*
Swine, Miniature
beta-Lactamases / biosynthesis*
Reg. No./Substance:
74469-00-4/Amoxicillin-Potassium Clavulanate Combination; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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