Screening and molecular characterization of plasmid-mediated fosfomycin resistance in Enterobacterales.

BACKGROUND: Fosfomycin, recently approved for intravenous use in several European countries for the treatment of soft-tissue, bloodstream, and urinary-tract infections, is increasingly threatened by resistance among Enterobacterales. This is particularly concerning for Escherichia coli, as fosfomycin often represents a last-resort option for urinary tract infections. To investigate the occurrence and genetic basis of resistance, 397 non-duplicate isolates (348 community-acquired and 49 hospital-acquired) were analyzed in a newly established hospital where there has been no use of fosfomycin. The isolates included Escherichia coli (n = 264), Klebsiella pneumoniae (n = 112), Enterobacter cloacae complex (n = 14), Klebsiella oxytoca (n = 6), Klebsiella aerogenes (n = 1).

METHODS AND RESULTS: Antimicrobial susceptibility testing and PCR screening for fosfomycin resistance genes revealed that only four E. coli isolates carried plasmid-mediated determinants, identified as fosA3 and fosA4, and confirmed by the sodium phosphonoformate (PPF) test. Mating-out and transformation assays showed no additional transferable fosfomycin resistance, suggesting that resistance in most Enterobacterales. was chromosomally encoded.

CONCLUSIONS: In newly established hospital settings, such screening approaches may enable early detection of carriers and help prevent the dissemination of plasmid-mediated fosfomycin resistance via IncF-type plasmids. Routine surveillance for fosfomycin resistance may therefore support infection control efforts and help preserve the clinical effectiveness of fosfomycin.