First Detection of Klebsiella pneumoniae Isolate Co-Harboring Fosfomycin Resistance Gene fosA3 and blactx-m Among Gram Negative Urine Isolates in a Turkish Hospital

The most common gram-negative pathogens in urinary tract infections are Escherichia coli and Klebsiella pneumoniae. Therapy that is often empirical relies on local antibiotic resistance data, hence monitorization of antimicrobial resistance periodically in each hospital is a requirement. In this study, antibiotic susceptibility profiles of consecutive urinary isolates (E. coli [n = 235] and K. pneumoniae [n = 56]) of adult patients collected between February 2018 and February 2019 from inpatients in Hacettepe University Hospital were assessed. Isolates resistant to fosfomycin (minimum inhibitory concentration >32 mg/L) were further investigated for the presence of fosA, fosA3, and fosC2. Fosfomycin susceptibility was determined by agar dilution method. Broth microdilution method was performed for amikacin, gentamicin, ceftazidime, ceftriaxone, meropenem, ciprofloxacin, tigecycline, trimethoprim/sulfamethoxazole (TMP/SMX), colistin, and piperacillin/tazobactam (PIP/TAZ). PCR method was employed to investigate fosA, fosA3, fosC2, and bla(CTX-M). Existence of fosA3 gene was confirmed by sequencing. Resistance rates to amikacin, gentamicin, ceftazidime, ceftriaxone, meropenem, ciprofloxacin, tigecycline, TMP/SMX, colistin, and PIP/TAZ were 2.7%, 18.5%, 25.4%, 33.0%, 3.4%, 45.4%, 2.4%, 43.6%, 6.2%, and 23.7%, respectively. Sixteen isolates (5.5%) were resistant to fosfomycin. Resistance was most frequently observed in K. pneumoniae (n = 9). fosA3 gene was detected in one fosfomycin-resistant K. pneumoniae isolate. This isolate also carried bla(CTX-M.) fosC2 and fosA genes could not be detected in any of the isolates. In this study, we report for the first time the existence of fosA3 in Turkey and its association with the bla(CTX-M) gene. As a result of increasing bla(CTX-M) producing Enterobacterales isolates globally, increase in fosfomycin resistance may be expected in near future.