title: Comparative activity of meropenem against Pseudomonas aeruginosa strains with well-characterized resistance mechanisms.
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.
authors.affiliation: Department of Medical Microbiology, The London Hospital Medical College, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yang
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000096:biosynthesis; D015780:Carbapenems / Q000494:pharmacology*; D002228:Carbenicillin / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004251:DNA Transposable Elements; D004352:Drug Resistance, Microbial; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D005798:Genes, Bacterial; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics; D013845:Thienamycins / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D015780:Carbapenems; D004251:DNA Transposable Elements; D013845:Thienamycins; D015378:Imipenem; D001618:beta-Lactamases; D000077731:Meropenem; D002228:Carbenicillin