Beta-lactamase evaluation of the amoxycillin-clavulanate association.
The capability of potassium clavulanate to protect amoxycillin from destruction by three partially purified beta-lactamases (from E. cloacae, B. cereus 569/H9 and E. coli R-TEM) was evaluated. The enzymatic inhibition was determined spectrophotometrically by assessing the ability of either amoxycillin or potassium clavulanate or their combination (at a 7:1 ratio by weight) to prevent the hydrolysis of a chromogenic substrate (nitrocefin) after different pre-incubation times, thus determining the IC50 and Ki values. Potassium clavulanate significantly reduced the IC50 values of amoxycillin for B. cereus and TEM enzymes by a factor ranging from 500 to 1200, by inhibiting these beta-lactamases at concentrations ranging from 4 to 0.008 microM. However, clavulanic acid was quite ineffective against type I enzymes (from E. cloacae), while amoxycillin was found to be sufficiently stable (IC50 of 0.8-1.4 microM).
Novelli
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A
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Reali
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EF
Fallani
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Periti
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P
D000658:Amoxicillin / Q000378:metabolism / Q000494:pharmacology*; D001409:Bacillus cereus / Q000201:enzymology; D002969:Clavulanic Acids / Q000378:metabolism / Q000494:pharmacology*; D004754:Enterobacter / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*
D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D000658:Amoxicillin; D001618:beta-Lactamases