title: Genotypic characterization and in vitro activities of tigecycline and polymyxin B for members of the Enterobacteriaceae with decreased susceptibility to carbapenems.
abstract: Carbapenem resistance in members of the Enterobacteriaceae is increasing. To evaluate the effects of tigecycline and polymyxin B against carbapenem-non-susceptible pathogens, 89 representative clinical carbapenem-non-susceptible Enterobacteriaceae isolates were recovered from seven hospitals from four cities in China during 2006-2009: 30 Serratia marcescens, 35 Klebsiella pneumoniae, seven Enterobacter cloacae, six Enterobacter aerogenes, five Escherichia coli, four Citrobacter freundii and two Klebsiella oxytoca isolates. Twenty-eight S. marcescens isolates were indistinguishable. The 35 K. pneumoniae isolates belonged to 12 clonal strains. Among the 89 Enterobacteriaceae isolates, 82 produced KPC-2, seven produced IMP (three produced KPC-2 simultaneously), three did not produce any carbapenemases and nine were deficient in porins. Polymyxin B was much more active than tigecycline against carbapenem-non-susceptible Enterobacteriaceae. The MIC(50) and MIC(90) of imipenem, meropenem, ertapenem, polymyxin B and tigecycline were 8 and 32 µg ml(-1), 8 and 32 µg ml(-1), 16 and 128 µg ml(-1), 0.5 and 16 µg ml(-1), and 4 and 16 µg ml(-1), respectively. Rates of susceptibility to imipenem, meropenem, ertapenem and polymyxin B were 30.0%, 27.5%, 2.5% and 89.2% by CLSI criteria. The rate of susceptibility to tigecycline was 40% and 17.5% by Food and Drug Administration (MIC ≤2 µg ml(-1)) and European Committee on Antimicrobial Susceptibility Testing (MIC ≤1 µg ml(-1)) criteria, respectively. KPC-2- or IMP-producing E. coli transconjugants exhibited reduced susceptibility to carbapenems but were susceptible to polymyxin B and tigecycline with an MIC range of 0.5-2 µg ml(-1), 0.25-2 µg ml(-1), 0.5-4 µg ml(-1), 0.5 µg ml(-1) and 0.5-1 µg ml(-1). In conclusion, carbapenem resistance in Enterobacteriaceae is mainly due to production of KPC-2, and polymyxin B is active for the carbapenem-resistant Enterobacteriaceae.
authors.affiliation: Graduate School in Pharmaceutical Science, Osaka University, Japan.|Second Affiliated Hospital of Zhejiang University, 88 Jiefang Rd, Hangzhou 310009, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Second Affiliated Hospital of Zhejiang University, 88 Jiefang Rd, Hangzhou 310009, PR China.
authors.forename: Jia-Chang
authors.initials: JC
authors.lastname: Cai
authors.affiliation: Second Affiliated Hospital of Zhejiang University, 88 Jiefang Rd, Hangzhou 310009, PR China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhou
authors.affiliation: Graduate School in Pharmaceutical Science, Osaka University, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nasu
authors.affiliation: Second Affiliated Hospital of Zhejiang University, 88 Jiefang Rd, Hangzhou 310009, PR China.
authors.forename: Gong-Xiang
authors.initials: GX
authors.lastname: Chen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D015780:Carbapenems / Q000494:pharmacology*; D003227:Conjugation, Genetic; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D000078304:Tigecycline; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000078304:Tigecycline; C491478:beta-lactamase KPC-2; D001618:beta-Lactamases; D008911:Minocycline; D011112:Polymyxin B