title: Patterns of resistance associated with integrons, the extended-spectrum beta-lactamase SHV-5 gene, and a multidrug efflux pump of Klebsiella pneumoniae causing a nosocomial outbreak.
abstract: Multiresistant Klebsiella pneumoniae caused a nosocomial outbreak. Resistance patterns of the presumed outbreak isolates varied among and within patients. In order to control the outbreak, screening for extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae was commenced. A number of susceptible K. pneumoniae strains were stored to serve as controls in genetic strain typing. Typing by pulsed-field gel electrophoresis proved the clonality of the strains in the recognized outbreak patients. Typing of the control strains by pulsed-field gel electrophoresis showed that at least one patient had been missed by the ESBL screening procedure. Further genetic typing confirmed the presence of the SHV-5 ESBL gene in all but one of the outbreak strains. Variable presence of integrons that carried the aminoglycoside resistance genes aadB and aadA2 was found. A gyrA mutation in codon 83 was present in all outbreak strains tested, despite considerable differences in ciprofloxacin MICs. The MICs of ciprofloxacin and the chemically unrelated drug cefoxitin were correlated (r = 0.86, P < 0.01) and were compatible with the overexpression of an efflux pump in a subset of the outbreak strains. We conclude that outbreak strains that express an ESBL gene only at a low level may pass unnoticed in a screening procedure, when the laboratory is unaware of variable ESBL expression. In this particular outbreak, screening for strains for which ciprofloxacin MICs were > or =0.25 micro g/ml would in retrospect have been the most sensitive method for detection of the K. pneumoniae outbreak strain.
authors.affiliation: Municipal Public Health Laboratory, Amsterdam. Zuiderzee Hospital, Lelystad, The Netherlands. pgruteke@gggd.amsterdam.nl
authors.forename: Paul
authors.initials: P
authors.lastname: Gruteke
authors.forename: Wil
authors.initials: W
authors.lastname: Goessens
authors.forename: Jan
authors.initials: J
authors.lastname: Van Gils
authors.forename: Paul
authors.initials: P
authors.lastname: Peerbooms
authors.forename: Nicole
authors.initials: N
authors.lastname: Lemmens-Den Toom
authors.forename: Marga
authors.initials: M
authors.lastname: Van Santen-Verheuvel
authors.forename: Alex
authors.initials: A
authors.lastname: Van Belkum
authors.forename: Henri
authors.initials: H
authors.lastname: Verbrugh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D032023:Integrons / Q000235:genetics*; D007710:Klebsiella Infections / Q000453:epidemiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D013223:Statistics as Topic; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000900:Anti-Bacterial Agents; C117193:beta-lactamase SHV-5; D001618:beta-Lactamases; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase