First Detection of the Plasmid-Mediated Fosfomycin Resistance Gene Fosa3 Among Phenotypically Fosfomycin-Resistant Uropathogens in Ibadan, Nigeria: A Cross-Sectional Molecular Surveillance Study

The plasmid-borne fosA3 gene, which encodes a fosfomycin-modifying enzyme, is the most common transferable cause of fosfomycin resistance worldwide. Data from sub-Saharan Africa are almost non-existent, and no previous Nigerian study has screened uropathogens for this gene. We therefore examined the occurrence of fosA3 among fosfomycin resistant urinary isolates at a Nigerian tertiary hospital and how well its presence matches phenotypic resistance.
In this study, 112 archived uropathogens from University College Hospital (UCH), Ibadan were tested for fosfomycin susceptibility by glucose-6-phosphate-supplemented disk diffusion using EUCAST v14.0 breakpoints. All 22 phenotypically resistant isolates were screened by conventional PCR for fosA3 and the chromosomal comparator fosA; phenotypically susceptible isolates were not PCR-tested and were assumed gene-negative for the concordance analysis.
Of the 112 isolates (61.6% Escherichia coli), 22 (19.6%, 95% CI 13.3–28.0%) were fosfomycin resistant. fosA3 was found in 7 of these 22 isolates (31.8%, 95% CI 16.4–52.7%), five isolates (22.7%) carried both genes. Under the assumption that untested susceptible isolates were gene-negative, detection of fosA3 alone gave 100% specificity and positive predictive value for phenotypic resistance but only 31.8% sensitivity. Combining fosA and/or fosA3 raised sensitivity to 77.3% while keeping 100% specificity (χ² = 76.098, df = 1, p < 0.0001). The remaining 22.7% of resistant isolates were negative for both genes, pointing to non-enzymatic resistance mechanisms.
This is the first report of fosA3 in Nigeria and one of the earliest in sub-Saharan West Africa. Plasmid-mediated fosfomycin resistance is already present in the uropathogen population of a Nigerian tertiary hospital. Molecular surveillance for fosA3 should be added to local antimicrobial-resistance monitoring, together with continued phenotypic testing to catch gene-negative resistance.

fosA3; fosfomycin resistance; plasmid-mediated resistance; uropathogens; antimicrobial resistance surveillance

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