INHIBITORY ACTIVITY OF VARIOUS CONCENTRAT IONS OF CLAVULANIC ACID, TAZOBACTAM AND SULBACTAM AGAINST 117 BETA-LACTAMASE-PRODUCING ENTEROBACTERIACEAE STRAINS

Enzymatic inactivation (betalactamases) is the most frequent type of r esistance to betalactam antibiotics, be it natural or acquired, at lea st among gram-negative species. The choice of betalactamase inhibitor can be important, given the factors that influence the degree of syner gy (diffusion across the bacterial wall, stability of the inhibitor, n ature of the betalactamase and the amount produced, etc.). In this stu dy, we compared the activities of three inhibitors (clavulanic acid, t azobactam and sulbactam) at 2, 4 and 8 mg/l, in combination with ampic illin, amoxycillin, ticarcillin and piperacillin against 117 Enterobac teriaceae strains (Escherichia coli, E. hermannii, Klebsiella pneumoni ae, K. oxytoca, Citrobacter diversus, C. freundii, Proteus vulgaris, P . mirabilis, P. rettgeri, P. stuartii, Morganella morganii and Serrati a marcescens). All the strains were resistant to amoxicillin and produ ced various types of betalactamases : chromosome- and/or plasmid-borne penicillinases (TEM), cefuroximases, extended broad-spectrum betalact amases (EBS) and inhibitor-resistant betalactamases (TRI). In vitro an tibacterial activity (MIC) and the synergistic effect (MIC ratio in th e presence and absence of the inhibitor, SR) varied according to the b acterial species, the type of enzyme (chromosome- or plasmid-borne), t he amount produced and the concentration of the inhibitor. With the st rains in the low-level resistance group, with the exception of piperac illin, the SR varied little between the inhibitors (from 20 to 85), co ntrary to the high-level penicillinase phenotype (200 to 400 for clavu lanic acid and tazobactam, but only 15 for sulbactam). With the ticarc illin-resistant strains of the cephalosporinase phenotype, the SR vari ed according to the combination, from 65 to 340 with ticarcillin + cla vulanic acid or tazobactam, and from 6 to 25 with sulbactam. In contra st, it was low with the amino-penicillins (ampicillin and amoxycillin) for the combinations with clavulanic acid. With the EBS-producing str ains, the SR was very high (several hundred), regardless of the inhibi tor. Finally, all three inhibitors had very little activity against TR I-phenotype E. coli.