FDA approves fosfomycin for complicated urinary tract infections

The FDA has approved fosfomycin (Contepo) for injection for the treatment of adult patients with complicated urinary tract infections (cUTIs), including acute pyelonephritis, caused by susceptible isolates of Escherichia coli and Klebsiella pneumoniae, Meitheal Pharmaceuticals announced in a news release.¹

Fosfomycin is an IV-administered epoxide antibacterial antibiotic that has “demonstrated activity against gram-negative bacteria including Escherichia coli and Klebsiella pneumoniae that cause cUTIs,” the company noted. The agent has no known cross-resistance to other antibiotic classes.

"The rise of multi-drug-resistant pathogens poses a significant threat to our ability to combat infectious diseases, underscoring the continued need for novel therapies that target resistant organisms in patients having cUTIs," said Keith S. Kaye, MD, MPH Chief, Division of Allergy, Immunology and Infectious Diseases at the Robert Wood Johnson Medical School, in the news release.¹

The approval is supported by data from the phase 2/3 ZEUS (ZTI-01) trial (NCT02753946), which found that IV fosfomycin was noninferior to piperacillin/tazobactam in terms of the primary end point of overall success (defined as clinical cure and microbiological eradication) at the test of cure visit (day 19) in the microbiological intent-to-treat population. Specifically, overall success was achieved in 63.5% (108 of 170) patients in the fosfomycin arm vs 55.6% (94 of 169) in the piperacillin/tazobactam arm (treatment difference, 7.9; 95% CI, -3.1 to 18.9).

Overall, the ZEUS trial enrolled hospitalized patients with cUTI to assess the safety and efficacy of IV fosfomycin. Patients were randomly assigned to receive 6 g fosfomycin 3 times daily or 4.5 g piperacillin/tazobactam 3 times daily for 7 days. The primary end point was overall success, with clinical cure and microbiological eradication as secondary outcomes.

Fosfomycin was generally well-tolerated in the trial. The most common (2% or higher) adverse events in the fosfomycin arm included transaminase elevations (10.3%), hypokalemia (9.9%), neutropenia (6.4%), nausea (4.3%), diarrhea (3.9%), vomiting (3.9%), hypocalcemia (3.9%), hypernatremia (3.4%), headache (2.6%), and hypophosphatemia (2.1%).

“With an estimated three million cases of cUTIs treated in the hospital setting annually, there is a critical need for a safe and effective treatment option. CONTEPO’s safety, efficacy, and novel mechanism of action makes it a favorable new treatment option,” added Keith Robinson, MD, MS, FCCP, Chief Medical Officer of Meitheal Pharmaceuticals, in the news release.¹

The approval of fosfomycin marks the second approval of an antibiotic to Meitheal’s branded portfolio. In 2019, the company received approval for lefamulin (Xenleta) for adults with community-acquired bacterial pneumonia.³

“The escalating public health issue of antimicrobial resistance and emergence of highly resistant organisms demands immediate attention and innovative therapeutic solutions. The approval of CONTEPO is a major milestone in our company’s evolution and the fight against the ongoing threat of antibiotic resistance,” concluded Tom Shea, CEO of Meitheal Pharmaceuticals, in the news release.¹ “We are proud to add a second branded product to our growing portfolio of anti-infectives and antibiotics and look forward to delivering this high-quality and effective antibiotic medicine to patients and providers.”

REFERENCES

1. Meitheal Pharmaceuticals receives approval from the US Food and Drug Administration for CONTEPO™ (fosfomycin) for injection in patients ≥ 18 years having complicated urinary tract infections (cUTI), including acute pyelonephritis (AP). News release. Meitheal Pharmaceuticals. November 4, 2025. Accessed November 4, 2025. https://www.businesswire.com/news/home/20251104528525/en/Meitheal-Pharmaceuticals-Receives-Approval-from-the-US-Food-and-Drug-Administration-for-CONTEPO-fosfomycin-for-injection-in-Patients-18-Years-Having-Complicated-Urinary-Tract-Infections-cUTI-Including-Acute-Pyelonephritis-AP

2. Safety and efficacy of ZTI-01 (IV Fosfomycin) vs piperacillin/​tazobactam for treatment cUTI/​AP infections (ZEUS). ClinicalTrials.gov. Last updated March 7, 2019. Accessed November 4, 2025. https://clinicaltrials.gov/study/NCT02753946

3. Label. US Food & Drug Administration. Accessed November 4, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211672s000,211673s000lbl.pdf