Emergence of resistance in gram-negative bacteria during therapy with expanded-spectrum cephalosporins

To assess the clinical importance of emergence of beta-lactam resistance caused by stable derepression of chromosomal beta-lactamases, sequential cultures from patients treated with expanded-spectrum cephalosporins were monitored for the persistence of bacteria possessing these enzymes. Antibiotic susceptibilities and beta-lactamase production before and after cefoxitin induction were determined in sequential isolates of individual bacterial strains. Of 49 strains isolated from 44 patients, 25 strains (51%) were eradicated by cephalosporin therapy, 17 strains (35%) persisted with unchanged susceptibility in sequential cultures, and 7 strains (14%) from 7 patients developed multiple beta-lactam resistance during cephalosporin therapy. In 6 of the 7 strains, resistance was associated with stable derepression of beta-lactamases. In the patient group whose strains developed resistance, subsequent use of non-beta-lactam antibiotics was more frequent and mortality was higher.