Abstract
To investigate the efficacy of fosfomycin against extended-spectrum β-lactamases (ESBL) producing Escherichia coli in Taiwan and the resistance mechanisms and characterization of human and pig isolates, we analyzed 145 ESBL-producing isolates collected from two hospitals (n = 123) and five farms (n = 22) in Taiwan from February to May, 2013. Antimicrobial susceptibilities were determined. Clonal relatedness was determined by PFGE and multi-locus sequence typing. ESBLs, ampC, and fosfomycin resistant genes were detected by PCR, and their flanking regions were determined by PCR mapping and sequencing. The fosfomycin resistant mechanisms, including modification of the antibiotic target (MurA), functionless transporters (GlpT and UhpT) and their regulating genes such as uhpA, cyaA, and ptsI, and antibiotic inactivation by enzymes (FosA and FosC), were examined. The size and replicon type of plasmids carrying fosfomycin resistant genes were analyzed. Our results revealed the susceptibility rates of fosfomycin were 94% for human ESBL-producing E. coli isolates and 77% for pig isolates. The PFGE analysis revealed 79 pulsotypes. No pulsotype was found existing in both human and pig isolates. Three pulsotypes were distributed among isolates from two hospitals. ISEcp1 carrying bla CTX-M-group 9 was the predominant transposable elements of the ESBL genes. Among the thirteen fosfomycin resistant isolates, functionless transporters were identified in 9 isolates. Three isolates contained novel amino acid substitutions (Asn67Ile, Phe151Ser and Trp164Ser, Val146Ala and His159Tyr, respectively) in MurA (the target of fosfomycin). Four isolates had fosfomycin modified enzyme (fosA3) in their plasmids. The fosA3 gene was harboured in an IncN-type plasmid (101 kbp) in the three pig isolates and an IncB/O-type plasmid (113 kbp) in the human isolate. In conclusion, we identified that 6% and 23% of the ESBL-producing E. coli from human and pigs were resistant to fosfomycin, respectively, in Taiwan. No clonal spread was found between human and pig isolates. Functionless transporters were the major cause of fosfomycin resistance, and the fosA3-transferring plasmid between isolates warrants further monitoring.
Highlights
The emerging problem of extended-spectrum β-lactamases (ESBLs) producing Enterobacteriaceae has been reported worldwide [1,2]
Falagas et al reported that fosfomycin could be a solution to this problem; the susceptibility to fosfomycin was 96.8% (1604/1657) in ESBL-producing Escherichia coli and 81.3% (608/748) in Klebsiella pneumoniae in a systemic review [3]
Three pulsotypes appeared in both hospitals, including pulsotype XXIX (n = 5, 4 from Kaohsiung Medical University Hospital (KMUH) and 1 from Pingtung Hospital (PTH)), XXXIV (n = 8, 2 from KMUH and 6 from PTH) and XLIV (n = 25, 21 from KMUH and 4 from PTH)
Summary
The emerging problem of extended-spectrum β-lactamases (ESBLs) producing Enterobacteriaceae has been reported worldwide [1,2]. Recent studies have focused on the disseminative fosfomycin resistant genes These reports revealed fosA3 genes were flanked by IS26 and were localized on conjugative plasmids for human isolates in Japan [13,14], Korea [12], and another fosA variant (fosKP96) was found in Hong Kong [8], while some studies have focused on livestock or animal isolates from different regions of China [9,10,11]. We aimed to identify fosfomycin resistance and its underlying mechanisms and characterization of ESBL-producing E. coli isolates from human and pig sources in Taiwan
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