High Cure Rates, Microbiologic Eradication With IV Fosfomycin
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SAN DIEGO—Intravenous (IV) fosfomycin (ZTI-01) is effective and tolerated in hospitalized adults for the treatment of complicated urinary tract infections (cUTI) including acute pyelonephritis (AP), according to findings from the multi-center, randomized, double-blind, Phase 2/3 ZEUS study, reported at IDWeek.
"ZTI-01 (fosfomycin for injection) was non-inferior to P-T in overall success among patients with cUTI and AP," reported lead author Paul B. Eckburg, MD, from Zavante Therapeutics, Inc., San Diego, CA, and coauthors. "Among treatment arms, cure rates were high and microbiologic eradication rates favored ZTI-01."
IV fosfomycin is a novel epoxide antibiotic injection with a distinct mechanism of action that inhibits an early step in the bacterial cell wall synthesis. ZEUS was a multi-center, randomized, double-blind study (n=465) that evaluated IV fosfomycin vs. piperacillin/tazobactam. The primary endpoint was overall success defined as clinical cure plus microbiologic eradication in the microbiologic modified intent-to-treat (mITT; n=464) population at the test-of-cure (TOC) visit (Day 19).
Study patients were randomized to IV fosfomycin 6g infused over 1 hour every 8 hours (total dose 18g daily) or IV piperacillin/tazobactam 4.5g infused over 1 hour every 8 hours (total dose 13.5g daily) for a fixed 7 days. Patients with concurrent bacteremia were treated for up to 14 days. The authors noted that oral-step down therapy was not allowed.
Treatment with IV fosfomycin met the primary objective of non-inferiority compared to piperacillin/tazobactam. The overall success rate was 64.7% with fosfomycin vs. 54.5% with piperacillin/tazobactam (treatment difference 10.2%, 95% CI: -0.4, 20.8).
Clinical cure rates at Day 19 were "high and similar between treatment groups" (90.8% vs. 91.6%, respectively), the authors reported. IV fosfomcyin was also well tolerated in general among the safety population. Treatment-emergent adverse events (TEAEs) were seen in 42.1% of fosfomycin patients and 32.0% of piperacillin/tazobactam patients; most TEAEs were reported to be mild and transient.
The findings from ZEUS support the tolerability and efficacy of fosfomycin in patients with cUTI and AP. Dr. Eckburg added, "If approved in the US, ZTI-01 would provide a new IV therapeutic option with a unique MOA for patients with difficult to treat Gram-negative infections."
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Eckburg, PB. Intravenous Fosfomycin (ZTI-01) for the Treatment of Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP): Results from a Multi-center, Randomized, Double-Blind Phase 2/3 Study in Hospitalized Adults (ZEUS). Poster presented at IDWeek; October 4–8, 2017; San Diego, CA. http://www.idweek.org