Multiple-Dose Fosfomycin for Complicated UTIs

In cases of complicated urinary tract infections (UTI) treated with multiple-dose fosfomycin, clinical resolution occurred in 2 of 3 treatment episodes and bacteriologic resolution in one-half of treatment episodes, according to study results published in Open Forum Infectious Diseases.

There are few studies describing the off-label use of multiple-dose fosfomycin for outpatient treatment of complicated UTI. To characterize the patients, infections, drug susceptibilities, and outcomes of multiple-dose fosfomycin episodes, investigators conducted a retrospective study evaluating patients with UTIs who received an outpatient prescription for multiple-dose fosfomycin between July 1999 and June 2018. Prescriptions dispensed for UTI prophylaxis were excluded.

Of the 171 multiple-dose fosfomycin treatment episodes included in the study, the most common regimen was a single dose every 3 days, with a mean treatment duration of 6.1 days. Clinical resolution was demonstrated in 66.1% of episodes; bacteriologic resolution occurred in 48.7% of 76 episodes with post-treatment cultures. Before treatment, most patients used antibiotics (81.9%) or had urine cultures (97.7%). Within 90 days post-treatment the use of additional antibiotics occurred in 51.5%, urine cultures in 66.1%, and healthcare utilizations in 24.6% of patients.

According to the investigators, this study is to their knowledge, “the largest to date assessing the utility and outcomes related to MDF regimens in complicated UTI in the outpatient setting.” However, several study limitations must also be noted. Theretrospective cohort design of the study did not allow for a determination of causality, but does justify future prospective study of multiple-dose fosfomycin treatment and outcomes. This was also a single arm study and treatment regimens were not compared with other UTI treatments. The choice of therapy, duration of treatment, and subsequent monitoring were at the discretion of the prescriber. This does, however, reflect local clinical practice patterns, which potentially allows generalizability. Any patients not interacting with the healthcare system after the index date were assumed to have clinical resolution, meaning true rates may be overestimated. Furthermore, nonadherence may have affected the results. Given the small sample size with wide confidence intervals for some isolates it is also possible that future studies with larger sizes may produce different results. Finally, the rate of bacteriologic resolution may have been affected as UTIs occurring within the follow-up period were not specifically characterized as bacteriologic relapse or reinfection.

The results of the study did show that in patients with complicated infections and multiple prior UTI treatment episodes, multiple-dose fosfomycin treatment was associated with clinical resolution in 2 of 3 treatment episodes and bacteriologic resolution in one-half of treatment episodes. Infections caused by Escherichia coli, Pseudomonas spp, and Klebsiella spp were the most likely to respond to treatment.

The investigators recommended that when considering this treatment, “clinicians should consider obtaining post-treatment cultures to verify successful treatment and guide the need for subsequent additional management.” They also stated that future prospective studies to determine the relative efficacy and safety, optimal dosing regimen and duration, and ideal population for use are needed.

Reference

Derington CG, Benavides N, Delate T, Fish DN. Multiple-dose oral fosfomycin for treatment of complicated urinary tract infections in the outpatient setting. Open Forum Infect Dis. 2020;7:ofaa034.