Contribution of efflux to cefuroxime resistance in clinical isolates of Escherichia coli.

Retrospective data showed that resistance to cefuroxime among clinical blood culture isolates of Escherichia coli (2.67%) was more common than resistance to cefotaxime (0.59%) and ceftazidime (1.48%). 30 clinical isolates of E. coli with various degrees of resistance to cefuroxime were selected for the present studies. Antibiotic susceptibility to beta-lactam antibiotics was determined with the disc-diffusion method and for cefuroxime also with the E-test. The ability to grow in the presence of organic solvents was determined as a phenotypical measure of efflux. The organic solvent tolerance (OST) was graded on a scale from 1 to 5. Antibiotic susceptibility to cefuroxime, cefotaxime, ceftazidime and loracarbef was also determined in the presence of a known efflux pump inhibitor, MC-207,110. The strains that were organic solvent tolerant had significantly higher minimal inhibitory concentration (MIC) values for cefuroxime than the other E. coli strains (median 24 mg/l, range 4 to >256 mg/l vs median 4 mg/l, range 2-64 mg/l) and significantly lower cefuroxime zone diameters (p<0.02). In the strains with most pronounced organic solvent tolerance, i.e. the cyclohexane-tolerant strains, the cefuroxime MIC values were decreased 2-fold (p<0.03) and the zone diameters increased (p<0.02) by the addition of an efflux pump inhibitor, MC-207,110. The findings supported the hypothesis that efflux contributes to cefuroxime resistance in E. coli.