title: In vitro assessment of the effect of clavulanic acid at concentrations achieved in human serum on the bactericidal activity of amoxicillin at physiological concentrations against Staphylococcus aureus: implications for dosage regimens.
abstract: The effects on Staphylococcus aureus viability and beta-lactamase activity of concentrations that simulated those in human serum after a combined dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro pharmacodynamic model. Six hours of preexposure to concentrations of the amoxicillin-clavulanic acid combination that were higher than the amoxicillin-clavulanic acid MIC led to a reduction of the initial inoculum of >90% and to a significant decrease of beta-lactamase activity versus those of the control even from 6 h, when concentrations were subinhibitory. The postantibiotic effect and post-beta-lactamase inhibitor effect contributed to these results.
authors.affiliation: Medical Department, SmithKline Beecham Pharmaceuticals, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Aguilar
authors.forename: M
authors.initials: M
authors.lastname: Martín
authors.forename: I P
authors.initials: IP
authors.lastname: Balcabao
authors.forename: M L
authors.initials: ML
authors.lastname: Gómez-Lus
authors.forename: R
authors.initials: R
authors.lastname: Dal-Ré
authors.forename: J
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000658:Amoxicillin / Q000097:blood / Q000494:pharmacology*; D019980:Amoxicillin-Potassium Clavulanate Combination; D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology*; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010406:Penicillins / Q000097:blood / Q000494:pharmacology*; D015610:Serum Bactericidal Test; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D010406:Penicillins; D019818:Clavulanic Acid; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D001618:beta-Lactamases