Antimicrobial Susceptibilities of Clinical Bacterial Isolates from Urinary Tract Infections to Fosfomycin and Comparator Antibiotics Determined by Agar Dilution Method and Automated Micro Broth Dilution

Uncomplicated bacteremic urinary tract infections (bUTIs) are common, often caused by Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, with most encounters treated empirically. As rates of antimicrobial resistance increase, available antibiotic treatment options are dwindling. Novel antibiotics approved for treating bUTIs are limited, leading to a resurgence of interest in older antibiotics, including fosfomycin. In this study, clinical urine samples from patients diagnosed with bUTIs from a military hospital on the Eastern Seaboard of the United States were tested for susceptibility to fosfomycin and comparator antibiotics, including levofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole (TMS). A total of 1353 nonduplicate bacterial isolates were tested. The majority were Gram-negative, including 605 non-ESBL and 285 ESBL E. coli and 84 non-ESBL and 52 ESBL K. pneumoniae. Fosfomycin susceptibility rates were similar for non-ESBL and ESBL E. coli (95.9% vs 96.1%) and K. pneumoniae (38.1% vs 36.5%). Fosfomycin demonstrated high activity against other Enterobacterales and Gram-positive organisms including Enterobacter faecalis and Staphylococcus aureus. Interestingly, most fosfomycin non-susceptible isolates were susceptible to other first-line bUTI treatment options, and most isolates that were non-susceptible to other first-line bUTI treatment option were susceptible to fosfomycin. ESBL K. pneumoniae isolates were the least susceptible to current first-line treatment options. Fosfomycin Etest demonstrated high sensitivity compared to agar dilution, making it a viable method in resource limited areas. Overall, we demonstrated fosfomycin has high activity against common etiologies that cause bUTIs. Further studies investigating the use of fosfomycin in treating non-E. coli bUTI pathogens, as single or combination therapy, is warranted.