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.