Extended broad-spectrum β-lactamases conferring transferable resistance to newer β-lactam agents in enterobacteriaceae: Hospital prevalence and susceptibility patterns

Abstract

Before 1985 at the Pitie-Salpetriere Hospital in Paris (2, 400 beds), resistance to cefotaxime in clinical isolates of Enterobacteriaceae involved only species producing inducible class βlactamase. Between November 1985 and April 1987, however, 62 isolates (57 of Klebsiella pneumoniae and five of Escherichia colii showed decreased susceptibility to cefotaxime(mean MIC, 8-16μg/mL). The transferabilityof cefotaxime resistance in E. coli KI2 was demonstrated for 15 of 16selected isolates. By isoelectric focusing using iodometric detection with 20 mg of ceftriaxone/100 mL and determination of substrate and inhibition profiles, three p-lactamases mediating cefotaxime resistance were identified as SHV-2(isoelectric point [pI] 7.6), CTX-I (pI 6.3), and “SHV-2-type” or SHV-3 (pI 6.98). The three p-lactamases hydrolyzed penicillins and cephalosporins (including cefotaxime and ceftriaxone) and weretherefore designated “extended broad-spectrum p-lactamases” (EBS-Bla). The enzymes conferred to derivatives a high levelof resistance to amoxicillin, ticarcillin, piperacillin, and cephalothin and a decreaseddegreeof susceptibility(i.e., MICs increasedby 10-to 800-fold)to cefotaxime, ceftriaxone, ceftazidime, and aztreonam. These p-lactamases did not affect the activity of cephamycins (cefoxitin, cefotetan, moxalactam) or imipenern. Synergy between clavulanate or sulbactam (2Ilg/mL) and amoxicillin was greater against derivatives producing EBS-Bla than against those producing TEM-I, TEM-2, or SHV-I; this synergywas greater with clavulanate than with sulbactam against derivativesproducing SHV-2and the SHV-2-type enzyme but wassimilar with clavulanate and sulbactam against those producing CTX-l. A double-disk synergy test performed with cefotaxime and Augmentin disks (placed 30 mm apart, center to center) seemed a useful and specific test for the detection of strains producing EBS-Bla. © 1988 by The University of Chicago.