Markedly different rates and resistance profiles exhibited by seven commonly used and newer β-lactams on the selection of resistant variants of Enterobacter cloacae

Seven beta-lactam antibiotics (cefepime, cefoperazone, ceftazidime, ceftriaxone, cefamandole, imipenem and meropenem) were tested for their potential to select resistance in standard and clinical strains of Enterobacter cloacae (n = 9). The strains were subcultured daily with the test antibiotics at doubling concentrations starting at 0.125 x MIC. Development of resistance throughout the passages was detected by a disc diffusion test. Ceftazidime, ceftriaxone and cefamandole selected resistance at a faster rate than cefoperazone, cefepime and meropenem. Imipenem did not select resistance in the nine strains tested and was the only antibiotic that eradicated all the strains during selection. The resistance patterns of strains selected by meropenem, cefepime and the other cephalosporins were markedly different, although cross-resistance to the early generation cephalosporins was common. The resistance phenotypes of most strains remained stable upon serial passages in antibiotic-free medium. The findings of this study highlight the importance of the choice of antibiotic for therapy not only on the basis of its antibacterial activity, but also on its potential to select resistance to itself and other antibiotics.