title: Relevance of resistance levels to carbapenems and integron-borne blaIMP-1, blaIMP-7, blaIMP-10 and blaVIM-2 in clinical isolates of Pseudomonas aeruginosa.
abstract: Molecular detection and surveillance of the resistance genes harboured by Pseudomonas aeruginosa are becoming increasingly important in assessing and controlling spread and colonization in hospitals, and in guiding the treatment of infections. This study analysed the resistance mechanisms of carbapenem-resistant clinical isolates of P. aeruginosa and identified the associated integron-borne metallo-beta-lactamase (MBL)-encoding genes. Twenty-seven imipenem (IPM)-resistant clinical isolates of P. aeruginosa were divided into three groups according to their resistance levels to carbapenems. Strains bearing bla(IMP-10) showed extremely high-level resistance to IPM, with MICs of 512-2048 microg ml(-1). By comparison, strains bearing bla(IMP-1), bla(IMP-7) and bla(VIM-2) showed an intermediate level of resistance, with MICs of 32-256 microg ml(-1). The non-MBL-producing strains showed a low level of resistance, with MICs of 8-32 microg ml(-1). The same trend in resistance levels was also observed when resistance to other carbapenems, such as meropenem and panipenem, was determined. DNA sequencing showed that the MBL-encoding gene cassettes were carried by class 1 integrons. The bla(IMP-1), bla(IMP-7) and bla(IMP-10) gene cassettes were preceded by a hybrid P(ant) promoter, TGGACA-N(17)-TAAACT, and the bla(VIM-2) gene cassette was preceded by a weak promoter, TGGACA-N(17)-TAAGCT. Most of the MBL-encoding genes were linked to one or two resistance genes encoding aminoglycoside-modifying enzymes, such as aac(6')Iae, aac(6')II, aacA7, aacC4, aadA1, aadA2 and aadA6, highlighting the multidrug-resistant properties of these clinical isolates.
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Zhao
authors.affiliation: Department of Clinical Pathology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Gelin
authors.initials: G
authors.lastname: Chen
authors.affiliation: Clinical Laboratory, Showa University Hospital, Showa University, Tokyo, Japan.
authors.forename: Ribu
authors.initials: R
authors.lastname: Ito
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Hu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D032023:Integrons; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases