Fosfomycin has been used off-label in multiple dose regimens to treat uncomplicated and complicated urinary tract infections caused by multidrug-resistant organisms. The agent is an attractive treatment option because it is administered orally, has low resistance rates, and rarely interacts with other drugs.
However, few published studies describe off-label use of multiple doses of fosfomycin for treating complicated urinary tract infections (cUTIs).
To address this need for information, a team of investigators from Kaiser Permanente and University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences conducted a study to characterize patients, infections, drug susceptibilities, and patient outcomes associated with multiple doses of fosfomycin. Their findings were published in Open Forum Infectious Diseases
The retrospective study evaluated patients who received an outpatient prescription for multiple-dose fosfomycin between July 1999 and June 2018 at Kaiser Permanente Colorado. Multiple-dose fosfomycin prescriptions dispensed for UTI prophylaxis were excluded.
The primary outcome of the study was complete resolution of signs and symptoms of infection within 30 days.
The study team also assessed secondary outcomes, including descriptions of antibiotics and cultures before and after treatment, 30-day bacteriologic resolution (post-treatment urine culture <103
colon-forming units of the original pathogen), and 90-day health care utilizations for incidence of cUTI or pyelonephritis.
The investigators found that of 171 multiple-dose fosfomycin treatment occurrences, the most common regimen was 1 dose of the agent every 3 days for a mean duration of 6.1 days.
Among 171 episodes, clinical resolution occurred in 115 cases (67.3%). Bacteriologic resolution occurred in 37 of the of 76 cases with post-treatment cultures (48.7%).
The study team also observed that 81.9% of patients used antibiotics prior to treatment with fosfomycin. Additionally, 97.7% of patients had urine cultures before treatment.
When assessing post-treatment action, the study team found that within 90 days, antibiotic use, urine cultures, and health care utilizations occurred in 51.5%, 66.1%, and 24.6% of patients, respectively.
Overall, the study team observed that when using multiple doses of fosfomycin to treat cUTIs, clinical resolution occurred in 2 of 3 treatment occurrences and bacteriologic resolution occurred in one-half of treatment episodes.
The authors of the report also noted that patients treated with multiple doses of fosfomycin were most often older women with at least 1 previous UTI, multiple comorbidities, and a history of repeated antibiotic exposure within the previous 90 days.
Additionally, the most common pathogens treated with fosfomycin were Escherichia coli
spp., and Pseudomonas
spp. All pathogens were associated with high rates of nonsusceptibility to common antibiotics and multidrug-resistance was common.
“When considering [multiple-dose fosfomycin] for treatment of complicated UTI, clinicians should consider obtaining posttreatment cultures in order to verify successful treatment and guide the need for subsequent additional management,” the investigators wrote.
The authors also noted that future research is needed to determine the relative safety and efficacy along with optimal dosing regimen, duration, and population for treating cUTIs with multiple doses of fosfomycin.
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