title: High-level ciprofloxacin resistance from point mutations in gyrA and parC confined to global hospital-adapted clonal lineage CC17 of Enterococcus faecium.
abstract: To substantiate a common genetic background of ciprofloxacin-resistant Enterococcus faecium, 32 ciprofloxacin-resistant (Cip(r)) and 31 ciprofloxacin-susceptible (Cip(s)) isolates from outbreaks, clinical infections, surveillances, and animals from 10 different countries were genotyped by multilocus sequence typing. Additionally, susceptibilities to ampicillin and vancomycin and the presence of esp were determined and the quinolone resistance-determining regions of parC, gyrA, parB, and gyrE were sequenced. High-level Cip(r) (MIC > or = 64 microg/ml) due to point mutations in the quinolone resistance-determining region was unique to a distinct hospital-adapted genetic complex in E. faecium, previously designated CC17. Low-level Cip(r) (MIC = 4 microg/ml) in non-CC17 strains is not attributable to point mutations in any subunit of the topoisomerase genes, and the mechanism of resistance remains unclear. Acquisition of mutations in parC and gyrA, leading to high-level Cip(r), is, in addition to ampicillin resistance and the presence of a putative pathogenicity island, another cumulative step in hospital adaptation of CC17.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Internal Medicine, Eijkman-Winkler Institute, University Medical Center Utrecht, Heidelberglaan 100, Rm G04.614, 3584CX Utrecht, The Netherlands. h.leavis@azu.nl
authors.forename: Helen L
authors.initials: HL
authors.lastname: Leavis
authors.forename: Rob J L
authors.initials: RJ
authors.lastname: Willems
authors.forename: Janetta
authors.initials: J
authors.lastname: Top
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
mesh_terms: D001483:Base Sequence; D002939:Ciprofloxacin / Q000494:pharmacology*; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016984:Enterococcus faecium / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D005798:Genes, Bacterial; D044404:Genomic Islands; D005838:Genotype; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D008954:Models, Biological; D017354:Point Mutation; D014774:Virulence / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase