An IDSA Journal Club review in 2022 (see below) considered fosfomycin as “another oral option for complicated urinary tract infection with E. coli bacteremia in women,” based on an 2022 article published in Clinical Infectious Diseases. Updated 2026 IDSA guidance on the management of antimicrobial-resistant infections recommended oral fosfomycin for uncomplicated E. coli UTI treatment. But the guidance cautioned about use in complicated E. coli UTI therapy based on concerns for limited renal parenchymal and serum drug concentrations, calling for additional studies before oral fosfomycin should be considered for transition therapy for complicated UTIs. The guidance also added caution for the use of oral fosfomycin with non-E. coli Enterobacterales given high prevalence of FosA genes.
A recent study in the International Journal of Infectious Diseases randomized hospitalized men and women in Bangkok, Thailand, with a complicated UTI due to third-generation cephalosporin-resistant E. coli, C. freundii, E. cloacae or P. mirabilis to treatment with either an IV carbapenem or oral fosfomycin (dosed at 3 grams every 48 hours) to finish a seven-day total antibiotics course after completing three days of IV carbapenem. Patients were excluded if they were pregnant, had concurrent bacteremia, had co-infections in other organs, had a CrCl < 10, or had urinary bacteria that were resistant to study drugs.
The primary endpoint was clinical cure on day 7, defined as marked improvement of baseline signs and symptoms (like dysuria, urinary frequency or urgency, suprapubic pain, flank pain, fever) without the need for additional antimicrobial therapy.
Secondary outcomes included day 28 assessments of clinical cure, microbiological cure, hospital readmissions and adverse events. Microbiological cure was defined as the absence of the baseline uropathogen in follow-up urine cultures.
Out of the 124 cases that met inclusion criteria, the primary outcome was achieved in 98.4% of patients in both the carbapenem and oral fosfomycin groups, with no difference in clinical cures between the two treatment groups for primary and secondary outcomes.
Although the utility of oral fosfomycin in bacteremic patients with resistant strains of Enterobacterales was not explored in this study (but was included in the 2022 study), the authors were able to provide more evidence that complicated UTIs do not need prolonged IV therapy and can be safely treated with an IV-oral step-down strategy. This study also included 11 patients with non-E. coli pathogens who were successfully treated with oral fosfomycin, providing some evidence that more labs should test susceptibilities on urinary isolates of C. freundii, E. cloacae and P. mirabilis. However, because this study did not include bacteremic patients, the similar outcomes in both groups may reflect that only three days of IV therapy is needed to treat a complicated UTI without bacteremia, and step-down therapy may not be necessary.
(Angkanavisan et al. Int. J. Infect. Dis. Published online: May 29, 2026.)
Editor’s note: The IDSA Journal Club review below originally published Jan. 5, 2022.
Another oral option for complicated urinary tract infection with E. coli bacteremia in women
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 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 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.
(ten Doesschate et al. Clin Infect Dis. Published online: Nov. 16, 2021.)
