title: Orally administered colistin leads to colistin-resistant intestinal flora and fails to prevent faecal colonisation with extended-spectrum β-lactamase-producing enterobacteria in hospitalised newborns.
abstract: Colonisation and infection with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is an emerging problem. The aim of this study was to investigate whether colistin, which is reported to be effective against multiresistant enterobacteria, prevents ESBL-E colonisation in neonates. For prophylaxis of necrotising enterocolitis, oral gentamicin (15 mg/kg/day) is routinely used in all neonates hospitalised at the Neonatal Intensive Care Unit of University Hospital Graz (Austria). During the study period from May 2005 to September 2007, three ESBL-E outbreaks (total duration 18 months) occurred. During these outbreaks, gentamicin was immediately replaced by oral colistin (8 mg/kg/day) in all hospitalised neonates. All neonates colonised with ESBL-E during the study period were retrospectively analysed with regard to the influence of colistin on ESBL-E colonisation. Genetic relatedness of isolates was assessed by repetitive sequence-based polymerase chain reaction (rep-PCR). During the study period, 30 (4.5%) of 667 neonates were colonised with ESBL-E. Twelve of twenty-one patients colonised with Klebsiella pneumoniae (ESBL-Kp) and one of nine patients colonised with Klebsiella oxytoca (ESBL-Ko) had received oral colistin at time of colonisation with ESBL-E. Amongst ESBL-Kp, the rate of colistin resistance was significantly higher in the colistin group (P=0.0075). Four different clones of ESBL-Kp and three different clones of ESBL-Ko were isolated, indicating the occurrence of patient-to-patient transmission. Colistin-resistant as well as colistin-susceptible isolates were detected within the same clones, indicating induction of resistance. At the dosage used, oral colistin did not prevent colonisation with ESBL-E and appeared to select colistin-resistant strains or to induce colistin resistance.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. volker.strenger@medunigraz.at
authors.forename: Volker
authors.initials: V
authors.lastname: Strenger
authors.forename: Tanja
authors.initials: T
authors.lastname: Gschliesser
authors.forename: Andrea
authors.initials: A
authors.lastname: Grisold
authors.forename: Gernot
authors.initials: G
authors.lastname: Zarfel
authors.forename: Gebhard
authors.initials: G
authors.lastname: Feierl
authors.forename: Lilian
authors.initials: L
authors.lastname: Masoud
authors.forename: Martin
authors.initials: M
authors.lastname: Hoenigl
authors.forename: Bernhard
authors.initials: B
authors.lastname: Resch
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Müller
authors.forename: Berndt
authors.initials: B
authors.lastname: Urlesberger
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D019072:Antibiotic Prophylaxis / Q000379:methods*; D001317:Austria / Q000453:epidemiology; D015373:Bacterial Typing Techniques; D002353:Carrier State / Q000382:microbiology*; D016000:Cluster Analysis; D003091:Colistin / Q000008:administration & dosage*; D004196:Disease Outbreaks; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005838:Genotype; D006761:Hospitals; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D058889:Molecular Typing; D012189:Retrospective Studies; D012641:Selection, Genetic; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases; D003091:Colistin