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Int J Antimicrob Agents. 2002 Jan;19(1):75-8.

Experimental application of the median-effect principle for in vitro quantification of the combined inhibitory activities of clavulanic acid and imipenem against IRT-4 beta-lactamase.

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Laboratoire Universitaire de Thérapeutique, Service de Médecine Interne B, Hôpital Carémeau, rue du Professeur-Debré, 30029 Cédex, Nîmes, France.


Inhibitor-resistant TEM beta-lactamases (IRT) have been identified in Enterobacteriaceae which, however, remained susceptible to cephalosporins. We evaluated the combined inhibitory activity of clavulanic acid and imipenem at ratios of 1:1 and 1:3 against IRT-4, using the median effect principle of Chou and Talalay. The combination of the two drugs, which produced a nearly additive effect, meant their concentrations could be lowered 1.3-4.9-fold, while maintaining a 50% inhibitory effect against the IRT-4 in comparison with each drug alone. From a therapeutic point of view, such a combination is not efficient but this method of Chou and Talalay, used for the first time to assay combined inhibitory activity of beta-lactamase inhibitors, could be used to evaluate new molecules and/or strategies to inactivate beta-lactamase.

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