Emergence of resistance to carbapenem antibiotics in Pseudomonas aeruginosa

Meropenem is a new carbapenem antibiotic with activity similar to that of imipenem. Development of resistance to imipenem by Pseudomonas aeruginosa has occurred in therapy and is associated with loss of a 45,000-48,000 molecular weight outer membrane protein (OMP) and decreased imipenem penetration. Seven pairs of isolates of P. aeruginosa obtained before treatment and after emergence of resistance were examined for changes in MIC of both imipenem and meropenem, and for changes in OMP profile. Resistant mutants were obtained also from the pre-therapy strains on Mueller-Hinton agar containing increasing amounts of either drug, and maintained under antibiotic pressure. OMP preparations of all pre- and post-therapy strains and laboratory mutants were separated by polyacrylamide gel electrophoresis. Loss of a 45,000-48,000 molecular weight protein occurred in variants selected under carbapenem pressure and in all post-therapy isolates. Mero-penem remained four-fold more active than imipenem against the resistant strains and mutants