Effect of beta-lactam antibiotics on the in vitro development of resistance in Pseudomonas aeruginosa

Objective To investigate whether stepwise selection of resistance mutations may mirror the continued bacterial exposure to antibiotics that occurs in the clinical setting. Methods We examined the in vitro development of resistance to a number of c ommonly used antibiotics (cefepime, cefpirome, ceftazidime, cefotaxime, pip eracillin and imipenem) in Pseudomonas aeruginosa, a significant nosocomial pathogen. Stepwise resistance was assessed by serial passage of colonies l ocated nearest to the inhibition zone on antibiotic-containing gradient pla tes. Results The lowest frequencies of spontaneous resistance mutations were fou nd with cefepime and imipenem; these drugs also resulted in the slowest app earance of resistance of spontaneous resistance mutations. In five wild-typ e P. aeruginosa strains, cefepime-selected isolates required a mean of 30 p assages to reach resistance; resistance occurred more rapidly in strains se lected with other cephalosporins. P. aeruginosa strains that produced beta -lactamase or non-enzymatic resistance generally developed resistance more rapidly than wild-type strains. For most strains, resistance to all antibio tics except imipenem correlated with increased levels of beta -lactamase ac tivity. Cross-resistance of cephalosporin-selected resistant mutants Co oth er cephalosporins was common. Cephalosporin-resistant strains retained susc eptibility to imipenem and ciprofloxacin. Conclusions From our in vitro study, we can conclude that the rate of devel opment of resistance of P. aeruginosa is lower with cefepime compared with other cephalosporines.