High Rates of Fosfomycin Resistance in Gram-Negative Urinary Isolates from Israel

Increasing antimicrobial resistance is a major problem worldwide. Many urinary tract infection (UTI) isolates are resistant to all oral antimicrobial agents, necessitating intravenous treatment even for cystitis. Fosfomycin is a broad-spectrum antibiotic that achieves high and prolonged urinary drug concentration and is considered first-line treatment for uncomplicated cystitis. Our aim was to investigate fosfomycin susceptibility among urinary isolates and search for demographic or bacterial characteristics associated with fosfomycin nonsusceptibility. Materials and Methods: This is a retrospective study of all Gram-negative urinary isolates at Padeh-Poriya Medical Center in northern Israel. A total of 1503 isolates were tested for fosfomycin susceptibility, as well as susceptibility to other antimicrobial agents, by VITEK2 system and disk diffusion testing. Demographic and clinical data were obtained from patient electronic files. Results: A total of 1,503 isolates from patients' urine were included. Mean patient age was 64.6 years, 937 (62.3%) were female, 913 (60.7%) were Jews, and in 1,058 (70.4%) cases, the infection was community acquired; 28.1% were extended-spectrum beta lactamase (ESBL)-positive. A total of 1099 (73.1%) isolates were susceptible to fosfomycin. Fosfomycin nonsusceptibility was significantly correlated to year: 124 (20.7%) in 2015 versus 280 (30.9%) in 2016; patient age: 17.6% in patients ≤50 years versus 30% in patients >50 years; hospital-acquired UTI: 34.2% versus 23.8%; and presence of ESBL positivity: 31.1% in ESBL-positive versus 20.9% in ESBL-negative isolates (p for all <0.001). Conclusions: Fosfomycin nonsusceptibility among urine culture isolates is a worrisome phenomenon that is on the rise and is more often found in elderly patients, patients with nosocomial UTI, and isolates that are ESBL positive.