[Mechanisms of fosfomycin resistance of extended-spectrum β-lactamases-producing Escherichia coli and Klebsiella pneumoniae].

Objective To study the in vitro activity of fosfomycin to extended-spectrum β-lactamases (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae and to explore the mechanisms of fosfomycin resistance. Methods A total of 1 052 ESBLs-producing E. coli(ESBL-EC) and K. pneumoniae(ESBL-KP) isolates were collected from bloodstream infections of 28 hospitals of 22 provinces and municipalities, which were stored by our laboratory.Minimum inhibitory concentrations (MICs) of fosfomycin against these clinical isolates were determined by agar dilution methods according to the Clinical and Laboratory Standards Institute (CLSI)(2015). The genes related to fosfomycin resistance were confirmed by Polymerase Chain Reaction (PCR) and sequencing. Results The susceptibility rates of ESBL-EC and ESBL-KP isolates to fosfomycin were 91.3% (818/896) and 91.7% (143/156), respectively. A total of 91 fosfomycin-non-susceptible isolates were detected, of which 73 (80.2%) isolates carried fosA3 genes.Amongst 18 fosA3-negative isolates, 16 isolates were detected to have chromosomal mutations or insertion inactivation, while the rest two isolates had not been detected any resistant mechanisms. Conclusions Fosfomycin shows great in vitro antimicrobial activity to ESBL-EC and ESBL-KP. The primary mechanism of fosfomycin-non-susceptible isolates is fosA3 gene.Chromosomal mutations may also involve in the fosfomycin resistance. Key words: beta-Lactamases; Fosfomycin; Klebsiella pneumoniae; Escherichia coli