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

ABSTRACT 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. IMPORTANCE Uncomplicated bUTI are often caused by Escherichia coli , Klebsiella pneumoniae , and Enterococcus faecalis , and treated with antibiotics. As rates of antimicrobial resistance increase, the options available for treatment are diminishing. Limited novel antibiotics have entered the market leading to a resurgence of interest in older antibiotics, including fosfomycin. In this study, we investigated the susceptibility of bUTI clinical isolates to fosfomycin and current treatment. Isolates were susceptible to fosfomycin at similar or higher rates compared to comparator antibiotics, especially for isolates that produce extended-spectrum beta-lactamases. In addition to E. coli and E. faecalis , organisms that fosfomycin is FDA approved for, fosfomycin had high activity against other Enterobacterales and Gram-positive organisms including Staphylococcus aureus . Since most uncomplicated cystitis is treated empirically, fosfomycin is a reasonable treatment option, either single agent or in combination, supporting the need for randomized control trials to approve treatment of other etiologies, and harmonizing breakpoints across agencies.