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SAN DIEGO – A novel injectable antibiotic, fosfomycin (ZOLYD™, Zavante Therapeutics, Inc.), is safe and efficacious for the treatment of complicated urinary tract infections (cUTI), including acute pyelonephritis, according to research presented at IDWeek 2017.
In this multicenter phase 2/3 study, researchers compared the safety and efficacy of fosfomycin with that of piperacillin/tazobactam in 465 hospitalized adults with cUTI or acute pyelonephritis. Fosfomycin 6 g or piperacillin/tazobactam 4.5 g were administered by means of 1-hour intravenous infusions every 8 hours for 7 days. For patients with concurrent bacteremia, treatment was administered for 14 days. The primary end point was the rate of clinical cure and microbiologic eradication, defined as baseline bacterial pathogen(s) <104 CFU/mL on urine culture and negative repeat blood culture on day 19.
The primary end point of overall success for fosfomycin (64.7%) was non-inferior to piperacillin/tazobactam (54.5%; treatment difference, 10.2%; 95% CI, -0.4% to 20.8%). The clinical cure rates were also similar between groups (90.8% vs 91.6% for fosfomycin vs piperacillin/tazobactam).1
When the participants were divided into subgroups by baseline pathogen, Escherichia coli and Klebsiella pneumoniae were the most common; however, more than three-quarters of participants had more than one baseline pathogen. For both E coli and K pneumoniae baseline infections, the clinical cure rates and microbial eradication rates were similar between fosfomycin and piperacillin/tazobactam.2
A total of 42.1% of participants in the fosfomycin group and 32.0% in the piperacillin/tazobactam group experienced treatment-emergent adverse events. The majority of treatment-emergent adverse events were mild and included gastrointestinal disorders (10.7% vs 17.4% for fosfomycin vs piperacillin/tazobactam), investigations resulting from laboratory abnormalities (8.6% vs 3.5%), infections or infestations (7.3% vs 8.7%), and metabolism or nutrition disorders (7.3% vs 1.7%).3
“In an environment of rapidly increasing resistance, safe and effective antibiotics with activity against [multidrug-resistant] pathogens are sorely needed. If approved, ZOLYD’s unique mechanism of action and broad spectrum of activity would add to the treatment armamentarium when treating seriously ill patients in the hospital,” said Keith S. Kaye MD, MPH, professor of medicine at the University of Michigan Health System, in an interview with Infectious Disease Advisor.”
Authors have reported either being employed by or receiving consulting fees or research support from Zavante Therapeutics, Inc.
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- Kaye KS, Rice LB, Dane A, et al. 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). Presented at: IDWeek 2017; October 4-8, 2017; San Diego, CA. Poster 1845.
- Skarinsky D, Eckburg PB, Das A, Manvelian K, Ellis-Grosse EJ. Per pathogen outcomes from the ZEUS study, a multi-center, randomized, double-blind phase 2/3 study of ZTI-01 (fosfomycin for injection) versus piperacillin-tazobactam (P-T) in the treatment of patients with complicated urinary tract infections (cUTI) including acute pyelonephritis (AP). Presented at: IDWeek 2017; October 4-8, 2017; San Diego, CA. Poster 1833.
- Rice LB, Kaye KS, Dane A, et al. Safety results from the ZEUS Study: multi-center, randomized, double-blind phase 2/3 study in hospitalized adults with complicated urinary tract infections (cUTI) including acute pyelonephritis (AP) who received intravenous fosfomycin (ZTI-01). Presented at: IDWeek 2017; October 4-8, 2017; San Diego, CA. Poster 1837.