Factors determining resistance to beta-lactam combined with beta-lactamase inhibitors in Escherichia coli.

The influence of inoculum size, beta-lactamase hyperproduction (multicopy plasmid) and modifications in the outer membrane protein profile on the susceptibility of Escherichia coli to combinations of amoxycillin/clavulanate, amoxycillin/sulbactam, amoxycillin/tazobactam and piperacillin/tazobactam were studied. For all combinations the bacterial susceptibility was affected by factors determining an increase in beta-lactamase (inoculum size or hyperproduction). Clavulanic acid was the most efficient beta-lactamase inhibitor. The absence of the outer membrane proteins, OmpF and OmpC, did not significantly affect susceptibility to the combinations per se but when combined with the presence of beta-lactamase high MICs were observed. Seven out of eight amoxycillin/clavulanate resistant clinical isolates of E. coli had beta-lactamase hyperproduction and a decrease or absence of OmpF.