January 5, 2022
By Aldon Li, MD, FIDSA
The use of highly bioavailable antibiotics like trimethoprim-sulfamethoxazole or a fluoroquinolone for 7-14 days to treat pyelonephritis with or without bacteremia is standard practice. The Food and Drug Administration label indicates fosfomycin has low bioavailability and is used as an oral bactericidal antibiotic, prescribed as a single, one-time dose for treatment of uncomplicated urinary tract infections (UTIs) due to Escherichia coli and Enterococcus faecalis with diarrhea as a common adverse event after use.
A recent study in Clinical Infectious Diseases randomized hospitalized female adults with symptomatic, febrile E. coli UTI with either E. coli bacteriuria or E. coli bacteremia to treatment with either ciprofloxacin 500 mg twice daily or fosfomycin 3 g daily to finish a 10-day total antibiotics course after 1) completing 2-5 days intravenous (IV) therapy (2nd/3rd cephalosporin, amoxicillin +/- clavulanic acid, aminoglycoside, carbapenem, fluoroquinolone or trimethoprim-sulfamethoxazole) and 2) afebrile after 24 hours. Patients were excluded if a foley was placed prior to admission, they were pregnant, or they had a glomerular filtration rate < 30.
The primary endpoint was clinical cure at 6-10 days after completing a full 10-day antibiotic course, defined as being alive with reduction of symptoms without requirement of additional antibiotics.
The average IV therapy duration was 3.3 days (70% used an IV cephalosporin), and the average oral therapy duration was 6.7 days (49.5% received fosfomycin, and 50.5% received ciprofloxacin). Bacteremia occurred in 52% of the fosfomycin group and 51% of the ciprofloxacin group.
The authors found no difference in overall clinical cure between the groups, and in a post-hoc analysis, they found no difference in clinical cure in the bacteremic patients. The fosfomycin group had more gastrointestinal events.
Although the utility of oral fosfomycin in women with resistant strains of E. coli UTI was not fully explored in this study (extended-spectrum β-lactamase-producing E. coli was identified in only 6.2% of patients), the authors have pushed the boundaries of standard practice. Their study provides more evidence that complicated UTIs do not need prolonged IV therapy, that E. coli bacteremia from a controlled urinary source can be treated safely with an IV-oral step-down strategy, and that fosfomycin can be dosed daily for a duration of therapy much longer than the traditional 1-3 days.