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.
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.
Aguilar
L
L
Medical Department, SmithKline Beecham Pharmaceuticals, Madrid, Spain.
Martín
M
M
Balcabao
I P
IP
Gómez-Lus
M L
ML
Dal-Ré
R
R
Prieto
J
J
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
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D010406:Penicillins; D019818:Clavulanic Acid; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D001618:beta-Lactamases