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.