Emergence of Resistance to β-Lactam Agents in Enterobacteriaceae Species with Group I β-Lactamases in Spain

Abstract

ABSTRACT

The contribution of induction and stable derepression of chromosomal group I β-lactamases to β-lactam antibiotics resistance was studied in clinical isolates of Enterobacteriaceae, collected from patients treated with these antibiotics. Multiple isolates of the same species from the same patient were characterized by different typing methods. Sonicated extracts of cells were assayed for chromosomal and plasmid-mediated β-lactamases by isoelectric focusing and cloxacillin inhibition studies. The specific β-lactamase activity, basal and induced with cefoxitin, was determined to differentiate strains with inducible or derepressed production of the enzyme. Induction of β-lactamases was performed in each strain against the β-lactams used in the therapy of each patient. Older penicillins resulted in a moderate to strong increase in β-lactamase activity, whereas the results obtained with first-generation cephalosporins were species dependent. Expanded-spectrum cephalosporins were weak inducers of β-lactamases. Indeed, the use of cefotaxime for treatment preceded the appearance of strains that produced chromosomal group I β-lactamases constitutively. These strains showed a remarkable reduction in sensitivity to ureidopenicillins, carboxipenicillins, expanded-spectrum cephalosporins, and monobactams, but not to carbapenems.