Comparative activity of meropenem against Pseudomonas aeruginosa strains with well-characterized resistance mechanisms

J Antimicrob Chemother. 1989 Sep;24 Suppl A:149-59. doi: 10.1093/jac/24.suppl_a.149.

Abstract

Four major mechanisms cause resistance to beta-lactams in Pseudomonas aeruginosa: (i) cell wall impermeability gives broad-spectrum intrinsic resistance to all beta-lactams except imipenem, (i) loss of D-group outer membrane proteins correlates with narrow spectrum imipenem resistance, (iii) plasmid mediated beta-lactamases compromise antipseudomonal penicillins, cefoperazone and cefsulodin, and (iv) chromosomal beta-lactamase hyper-production compromises most beta-lactams except carbenicillin and imipenem. Meropenem was tested in vitro against P. aeruginosa isolates, mutants and transconjugants with these mechanisms. Meropenem had impaired activity (MIC 1-2 mg/l compared to 0.25 mg/l for sensitive isolates) for organisms with broad-spectrum intrinsic resistance. MICs of meropenem also were elevated (to 1-2 mg/l) for mutants with D2-protein-deficiency-associated imipenem resistance. Most plasmids encoding TEM, OXA or PSE beta-lactamases did not increase the MIC (0.12 mg/l) of meropenem for P. aeruginosa PU21. Decreased susceptibility (MIC 4 mg/l), however, was observed when plasmids coding the uncommon NPS-1, PSE-2 and OXA-3 enzymes were present in this strain. MICs of meropenem remained identical for chromosomal beta-lactamase-inducible P. aeruginosa strains and their enzyme-derepressed and basal mutants, indicating that the chromosomal beta-lactamase could not protect against the new carbapenem, regardless of its mode of expression.

Publication types

  • Comparative Study

MeSH terms

  • Bacterial Outer Membrane Proteins / analysis
  • Bacterial Outer Membrane Proteins / biosynthesis
  • Carbapenems / pharmacology*
  • Carbenicillin / pharmacology
  • Cell Membrane Permeability / drug effects
  • DNA Transposable Elements
  • Drug Resistance, Microbial
  • Gene Expression Regulation, Bacterial
  • Gene Expression Regulation, Enzymologic
  • Genes, Bacterial
  • Humans
  • Imipenem / pharmacology
  • Meropenem
  • Microbial Sensitivity Tests
  • Plasmids
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics
  • Thienamycins / pharmacology*
  • beta-Lactamases / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • Carbapenems
  • DNA Transposable Elements
  • Thienamycins
  • Imipenem
  • beta-Lactamases
  • Meropenem
  • Carbenicillin