Characterisation of fosfomycin resistance mechanisms and molecular epidemiology in extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates

Although fosfomycin is a treatment option for infections caused by extended-spectrum beta-lactamase (ESBL)producing Enterobacteriaceae, fosfomycin resistance has been documented. To our knowledge, fosfomycin resistance mechanisms in Klebsiella pneumoniae have not been systematically investigated. A total of 108 ESBL-producing K. pneumoniae isolates collected from Kaohsiung Medical University Hospital, Taiwan, from August 2012 to May 2013 were analysed in this study. Pulsed-field gel electrophoresis (PFGE) revealed 64 pulsotypes and six non-typeable isolates, indicating high genetic diversity. Moreover, pulsotypes V (n = 6), VII (n = 11) and LI (n = 4) belonging to ST11 were major types. Among 30 (27.8%) fosfomycin-non-susceptible isolates, 21 (70%) had a MurA amino acid substitution, and seven new variations increased the fosfomycin minimum inhibitory concentration (MIC) by 8- to 16-fold compared with wild-type MurA in Escherichia coli DH5 alpha.strain. Functionless transporters (GlpT and UhpT) with various mutations were found in 29 isolates (97%). No knownfosfomycin-modifying enzymes were detected in this study. The major resistance mechanisms to fosfomycin in K. pneumoniae were amino acid variations in the drug target and transporters. (C) 2016 Published by Elsevier B.V.