In-vitro susceptibility of Klebsiella oxytoca strains to 13 beta-lactams in the presence and absence of beta-lactamase inhibitors.

The susceptibility of Klebsiella oxytoca isolates was tested by an agar diffusion method (167 strains collected in six countries) and an agar dilution method (38 strains). Multivariate analysis of inhibition zone diameters by principal component analysis clearly individualised four susceptibility patterns, including the phenotype of strains overproducing beta-lactamase and resistant to penicillins, first-generation cephalosporins, cefuroxime and aztreonam, but susceptible to ceftazidime. This phenotype was different from that conferred by plasmid-mediated extended-spectrum beta-lactamases; strains expressing these enzymes were also resistant to ceftazidime and cefotaxime. The bla(oxy) gene from K. oxytoca was introduced into Escherichia coli and K. oxytoca recipients and conferred increased resistance to beta-lactams in the recipient cells. Clavulanic acid was effective in association with piperacillin (MIC decreased 36-fold), ceftriaxone (35-fold) and aztreonam (19-fold) against overproducing strains, in spite of a relatively high IC50 (0.3 microM). Sulbactam (IC50, 400 microM) was ineffective in this context when combined with piperacillin (MIC decreased 1.5-fold), ceftriaxone (1.6-fold) and aztreonam (1.6-fold). The inhibitory activity of tazobactam (IC50, 8.2 microM) was heterogeneous depending on the strain and the beta-lactam with which it was combined. When combined with piperacillin or ceftriaxone little potentiation in antibiotic activity occurred (MIC decreased 3.9-fold and 4.5-fold, respectively); however, tazobactam plus aztreonam resulted in a 50-fold decrease in MIC of antibiotic.