title: Effect of beta-lactam antibiotics on the in vitro development of resistance in Pseudomonas aeruginosa.
abstract: 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 commonly used antibiotics (cefepime, cefpirome, ceftazidime, cefotaxime, piperacillin and imipenem) in Pseudomonas aeruginosa, a significant nosocomial pathogen. Stepwise resistance was assessed by serial passage of colonies located nearest to the inhibition zone on antibiotic-containing gradient plates.
  
  
  RESULTS
  The lowest frequencies of spontaneous resistance mutations were found with cefepime and imipenem; these drugs also resulted in the slowest appearance of resistance of spontaneous resistance mutations. In five wild-type P. aeruginosa strains, cefepime-selected isolates required a mean of 30 passages to reach resistance; resistance occurred more rapidly in strains selected 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 antibiotics except imipenem correlated with increased levels of beta-lactamase activity. Cross-resistance of cephalosporin-selected resistant mutants to other cephalosporins was common. Cephalosporin-resistant strains retained susceptibility to imipenem and ciprofloxacin.
  
  
  CONCLUSIONS
  From our in vitro study, we can conclude that the rate of development of resistance of P. aeruginosa is lower with cefepime compared with other cephalosporines.
authors.affiliation: Archet Hospital, Nice, France. carsenti-etesse.h@chu-nice.fr
authors.forename: H
authors.initials: H
authors.lastname: Carsenti-Etesse
authors.forename: J D
authors.initials: JD
authors.lastname: Cavallo
authors.forename: P M
authors.initials: PM
authors.lastname: Roger
authors.forename: I
authors.initials: I
authors.lastname: Ziha-Zarifi
authors.forename: P
authors.initials: P
authors.lastname: Plesiat
authors.forename: E
authors.initials: E
authors.lastname: Garrabé
authors.forename: P
authors.initials: P
authors.lastname: Dellamonica
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D018550:Cephalosporin Resistance / Q000235:genetics; D002511:Cephalosporins / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D012692:Serial Passage; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D002511:Cephalosporins; D001618:beta-Lactamases