Every year in the United States, hundreds of thousands of people are hospitalized with complicated urinary tract infections caused by bacteria that have become resistant to most oral antibiotics — a category called ESBL-producing Enterobacterales. These infections currently require intravenous carbapenem antibiotics, typically delivered in a hospital or infusion center, because there are so few effective oral alternatives.
A randomized clinical trial published in Clinical Infectious Diseases and reported by CIDRAP has found that oral fosfomycin is noninferior to IV carbapenem antibiotics when used as a step-down or transition therapy for these drug-resistant infections — a finding that could meaningfully reduce both hospital stays and health care costs for one of the most common and increasingly troubling categories of antibiotic-resistant infection.
Why This Matters
Antimicrobial stewardship — the effort to use antibiotics more appropriately and efficiently to preserve their long-term effectiveness — has consistently identified the reduction of carbapenem use as a priority. Carbapenems are among the last-resort antibiotics for many resistant infections; overuse contributes to the development of carbapenem-resistant Enterobacterales (CRE), which leave physicians with almost no remaining treatment options.
Equally important from a patient perspective: requiring IV antibiotics for treatment completion keeps patients in hospitals or tied to infusion centers for days or weeks, with associated costs, inconvenience, infection risks from IV catheter placement, and disruption to normal life. A proven oral alternative that can be taken at home transforms a hospital-dependent treatment into an outpatient one.
What We Know So Far
ESBL-producing Enterobacterales are bacteria — primarily E. coli and Klebsiella pneumoniae — that produce enzymes (extended-spectrum beta-lactamases) that inactivate most penicillin and cephalosporin antibiotics, leaving very few effective treatment choices.
The trial was conducted at four tertiary hospitals in South Korea from November 2022 to June 2025, randomizing patients with complicated UTIs caused by ESBL-producing Enterobacterales who had already improved after three to seven days of IV carbapenem treatment — a "step-down" or transition therapy design. Among 299 patients enrolled, 152 received oral fosfomycin, and 147 continued IV carbapenem treatment. The primary outcome was clinical cure.
The results: clinical cure was achieved in 92.8% of the oral fosfomycin group and 95.2% of the IV carbapenem group — a risk difference of −2.47 percentage points that fell well within the prespecified noninferiority margin of 15 percentage points. Microbiologic cure rates and 30-day outcomes were similarly comparable between groups.
Fosfomycin is an older antibiotic used for decades in Europe for UTIs; it operates through a distinct mechanism from beta-lactam antibiotics and is not inactivated by ESBL enzymes. As the trial authors from Chosun University and the National Institute of Infectious Diseases noted: "Fosfomycin has favorable oral bioavailability and maintains activity against ESBL-producing Enterobacterales. Although approved only for acute uncomplicated cystitis, it is increasingly used off-label in clinical practice for complicated UTIs because of its preserved susceptibility profile."
What This Could Mean for Patients and Health Systems
If confirmed in broader populations and adopted into clinical practice, this finding could:
- Enable patients with ESBL UTI to complete their antibiotic course at home rather than in a hospital or infusion center
- Reduce hospital length of stay and the associated risks of hospital-acquired infections and IV catheter complications
- Reduce carbapenem use, supporting stewardship efforts and reducing selective pressure toward carbapenem-resistant organisms
- Reduce health care costs for a common and expensive hospitalization category
What the Evidence Shows — and What It Does Not
MedicalDaily Evidence Check
- Study type: Randomized controlled noninferiority trial
- Drug tested: Oral fosfomycin vs. IV carbapenem as step-down/transition therapy
- Patient population: Adults with complicated UTIs caused by ESBL-producing Enterobacterales, conducted at 4 tertiary hospitals in South Korea, N=299
- Published in: Clinical Infectious Diseases
- Primary finding: Clinical cure 92.8% (fosfomycin) vs. 95.2% (IV carbapenem); noninferior within the 15% margin
- What it does not prove: That oral fosfomycin should replace IV carbapenems as initial treatment; that it works equally well in all complicated UTI subtypes; or that it performs equally in immunocompromised patients, those with sepsis, or those with bloodstream infection (bacteremia)
- Geographic limitation: Trial conducted in South Korea — local antibiotic resistance patterns, fosfomycin susceptibility rates, and bacterial isolate characteristics may differ from U.S. settings
- Current guidance: This finding has not yet been incorporated into major infectious disease society guidelines; prescribers should consult their institution's antimicrobial stewardship program
What Doctors and Experts Say
Infectious disease specialists and antimicrobial stewardship pharmacists have long been interested in identifying oral options for ESBL UTIs that could safely replace IV carbapenems as step-down therapy. CIDRAP notes that fosfomycin's distinct mechanism of action, its activity against ESBL-producing bacteria, and its oral availability have made it a candidate for this role in European clinical practice, where it has more established use for complicated UTIs than in the United States. This trial provides the kind of prospective randomized evidence that U.S. infectious disease guidelines require before recommending a treatment change.
What You Can Do Now
If you or a family member has been diagnosed with an ESBL UTI requiring IV antibiotic treatment, ask your infectious disease physician or hospitalist about whether you might be a candidate for oral step-down therapy, including fosfomycin.
Patients should not self-medicate or request fosfomycin without proper evaluation — the appropriateness of oral step-down depends on the specific infection, the susceptibility of the bacteria to fosfomycin, and the patient's overall clinical status.
For health care providers: consult your institution's antimicrobial stewardship program for guidance on incorporating this data into transition therapy decisions pending guideline updates.
The Bottom Line
A randomized controlled trial found that oral fosfomycin is noninferior to IV carbapenem as transition therapy for complicated UTIs caused by drug-resistant ESBL-producing bacteria, with clinical cure rates of 92.8% versus 95.2%. If confirmed in broader and more geographically diverse populations and incorporated into clinical guidelines, this finding could shift a significant portion of inpatient IV treatment for a common, growing category of resistant infection to safer, cheaper, more convenient outpatient oral therapy. Ask your infectious disease physician about oral step-down options at your next relevant appointment.
