Emergence of resistance to beta-lactam agents in enterobacteriaceae species with group I beta-lactamases in Spain.

The contribution of induction and stable derepression of chromosomal group I beta-lactamases to beta-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 beta-lactamases by isoelectric focusing and cloxacillin inhibition studies. The specific beta-lactamase activity, basal and induced with cefoxitin, was determined to differentiate strains with inducible or derepressed production of the enzyme. Induction of beta-lactamases was performed in each strain against the beta-lactams used in the therapy of each patient. Older penicillins resulted in a moderate to strong increase in beta-lactamase activity, whereas the results obtained with first-generation cephalosporins were species dependent. Expanded-spectrum cephalosporins were weak inducers of beta-lactamases. Indeed, the use of cefotaxime for treatment preceded the appearance of strains that produced chromosomal group I beta-lactamases constitutively. These strains showed a remarkable reduction in sensitivity to ureidopenicillins, carboxipenicillins, expanded-spectrum cephalosporins, and monobactams, but not to carbapenems.

Emergence of resistance to beta-lactam agents in Pseudomonas aeruginosa with group I beta-lactamases in Spain.

The contribution of induction and stable derepression of chromosomal class I beta-lactamases to beta-lactam antibiotic resistance was studied in clinical isolates of Pseudomonas aeruginosa collected from patients treated with beta-lactam antibiotics. Multiple isolates from the same patient were characterized by O-serotyping as a primary screen, combined with pyocin typing. Sonicated extracts of cells were assayed for chromosomal and plasmid-mediated beta-lactamases by isoelectric focusing and cloxacillin inhibition studies. The specific beta-lactamase activity, basal and induced, with cefoxitin was determined to differentiate strains with inducible or derepressed production of the enzyme. Beta-lactamase induction was performed in each strain against the beta-lactam agents used in the therapy of each patient. The observations showed that induction against older penicillins such as penicillin, amoxicillin, and amoxicillin/clavulanate resulted in a moderate to strong increase in beta-lactamase activity, whereas the results obtained with first-generation cephalosporins varied with the beta-lactam agent tested. Third-generation cephalosporins were weak inducers of beta-lactamases, and their use as therapy preceded the appearance of strains that produce chromosomal group I beta-lactamases constitutively. These strains showed a remarkable reduction in sensitivity to ureidopenicillins, carboxipenicillins, third-generation cephalosporins, and monobactams, but not to carbapenems.

In vitro activity of biapenem against beta-lactamase producing Enterobacteriaceae.

The activity of biapenem was compared with that of imipenem and cefotaxime against 108 strains of beta-lactamase producing Enterobacteriaceae. Biapenem and imipenem were very active, inhibiting 90% of the strains at a concentration of 0.5 microgram/ml. Both carbapenems were very active against plasmidic beta-lactamase producers, with MIC90s below 1 microgram/ml. However, the MIC90 of biapenem for cephalosporinase producers was 1 microgram/ml. Against strains producing extended-spectrum beta-lactamases, biapenem exhibited better activity against TEM-type producers (MIC90 0.25 microgram/ml) than against SHV-type producers (MIC90 0.5 microgram/ml). Overall, the in vitro antibacterial activity of biapenem is similar to that of imipenem.