Investigation of the ability of newer beta-lactam antibiotics to select resistant mutants from Serratia marcescens after mutagenesis with nitrosoguanidine.

Resistant mutants could easily be selected from a nitrosoguanidine-treated culture of Serratia marcescens with piperacillin, cefotaxime, cefoxitin, cefotetan, latamoxef (moxalactam) and aztreonam. Imipenem on the other hand was significantly less effective in mutant selection. Resistant clones broadly fell into two distinct classes. Most mutants did not show increased beta-lactamase; their resistance seemed to be due to changed outer membrane proteins. Other mutants had strongly increased cephalosporinase activity, although the derepression was only partial. Piperacillin, cefotaxime and aztreonam preferentially selected the derepressed phenotype, whereas mutants selected with cefoxitin, cefotetan, moxalactam and imipenem were exclusively of the non-derepressed phenotype. There was a significant degree of cross-resistance between the beta-lactam antibiotics except imipenem which was only slightly less active against the membrane-altered mutants.