title: Distribution of Pseudomonas-Derived Cephalosporinase and Metallo-β-Lactamases in Carbapenem-Resistant Pseudomonas aeruginosa Isolates from Korea.
abstract: The emergence of carbapenem resistance among Pseudomonas aeruginosa is an increasing problem in many parts of the world. In particular, metallo-β-lactamases (MBLs) and AmpC β- lactamases are responsible for high-level resistance to carbapenem and cephalosporin. We studied the diversity and frequency of β-lactamases and characterized chromosomal AmpC β- lactamase from carbapenem-resistant P. aeruginosa isolates. Sixty-one carbapenem-resistant P. aeruginosa isolates were collected from patients in a tertiary hospital in Daejeon, Korea, from January 2011 to June 2014. Minimum inhibitory concentrations (MICs) of four antimicrobial agents were determined using the agar-dilution method. Polymerase chain reaction and sequencing were used to identify the various β-lactamase genes, class 1 integrons, and chromosomally encoded and plasmid-mediated ampC genes. In addition, the epidemiological relationship was investigated by multilocus sequence typing. Among 61 carbapenem-resistant P. aeruginosa isolates, 25 isolates (41.0%) were MBL producers. Additionally, 30 isolates producing PDC (Pseudomonas-derived cephalosporinase)-2 were highly resistant to ceftazidime (MIC50 = 256 μg/ml) and cefepime (MIC50 = 256 μg/ml). Of all the PDC variants, 25 isolates harboring MBL genes showed high levels of cephalosporin and carbapenem resistance, whereas 36 isolates that did not harbor MBL genes revealed relatively low-level resistance (ceftazidime, p < 0.001; cefepime, p < 0.001; imipenem, p = 0.003; meropenem, p < 0.001). The coexistence of MBLs and AmpC β-lactamases suggests that these may be important contributing factors for cephalosporin and carbapenem resistance. Therefore, efficient detection and intervention to control drug resistance are necessary to prevent the emergence of P. aeruginosa possessing this combination of β-lactamases.
authors.affiliation: Department of Biomedical Laboratory Science, Jeonju Kijeon College, Jeonju 560-701, Republic of Korea.
authors.forename: Hye Hyun
authors.initials: HH
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chungnam National University, Daejeon 301-721, Republic of Korea.
authors.forename: Gye Cheol
authors.initials: GC
authors.lastname: Kwon
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chungnam National University, Daejeon 301-721, Republic of Korea.
authors.forename: Semi
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chungnam National University, Daejeon 301-721, Republic of Korea.
authors.forename: Sun Hoe
authors.initials: SH
authors.lastname: Koo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D015780:Carbapenems / Q000494:pharmacology*; D002510:Cephalosporinase / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D016133:Polymerase Chain Reaction; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D062606:Tertiary Care Centers; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D002510:Cephalosporinase; D001618:beta-Lactamases; C063912:carbapenemase
keywords: AmpC β-lactamase; metallo-β-lactamase