LAUSR

The threat of antibiotic resistance has been increased dramatically during last few years, an old antibiotic agent, fosfomycin, has been re-introduced to fight against infections caused by Klebsiella pneumoniae carbapenemase -producing K. pneumonia (KPC-KP). However, the trend of fosfomycin resistance among KPC-KP strains is increasing. Eighty KPC-KP clinical isolates were collected from three teaching hospitals during 2014 and 2017 in China. The strains were subjected to whole genome sequencing (WGS). The fosfomycin resistance phenotype and mechanisms were investigated by antimicrobial susceptibility testing and carbon source growth test, respectively. In all KPC-KP strains, 80% (64/80) strains were resistance to fosfomycin and 36.3% (29/80) strains were positive for mobile fosfomycin resistance gene fosA3. Among the 63 strains that were unable to grow in M9 basic medium with glycerol-3-phosphate as the sole carbon source (mutation of the target gene glpt mediated), there was no significant difference regarding to the MIC distribution of fosfomycin between fosA3-positive strains and fosA3-negative strains (P=0.577). Among the 50 strains which were negative for fosA3 but positive for fosA, the MICs of fosfomycin of strains that were unable to grow in M9 basic medium with glycerol-3-phosphate as the sole carbon source were significantly higher than (P<0.001) the strains that were able to grow in M9 basic medium with glycerol-3-phosphate as the sole carbon source. Our findings indicate that fosfomycin resistance among KPC-KP in China was an emerging problem, and the two major mechanisms of resistance identified were plasmid-mediated fosfomycin resistance gene fosA3 and mutation of the target gene glpt.