This article is more than 5 years old. Information may no longer be current.
IV fosfomycin effective in treating complicated UTIs
Click Here to Manage Email Alerts
The IV formulation of fosfomycin was found to be effective in treating complicated UTIs, including acute pyelonephritis, compared with IV piperacillin-tazobactam, according to research published in Clinical Infectious Diseases
“Fosfomycin has a broad spectrum of activity, and often retains activity against multidrug-resistant gram-negative and gram-positive bacteria,” Infectious Disease News Editorial Board Member Keith S. Kaye, MD, MPH, director of clinical research in the division of infectious disease at the University of Michigan, told Infectious Disease News. “Although the oral formulation has been available in the United States for years and the intravenous formulation has been available in Europe for decades, the intravenous formulation of fosfomycin is not approved for use in the U.S.”
Kaye and colleagues conducted a phase 2/3 multicenter trial named ZEUS, in which hospitalized adults with suspected or confirmed complicated UTIs and acute pyelonephritis (AP) were randomly assigned IV fosfomycin (ZTI-01; n = 233) or IV piperacillin-tazobactam (PIP-TAZ; n = 231). The dosage was 6 g ZTI-01 every 8 hours or 4.5 g IV PIP-TAZ every 8 hours for a fixed 7-day course, with no oral switch. Patients who experienced concomitant bacteremia could receive 14 days of treatment.
The researchers reported that ZTI-01 met the primary endpoint, which was a composite of clinical cure plus microbiologic eradication in the microbiologic modified intent-to-treat population (m-MITT) at the test of cure (TOC) compared with PIP-TAZ. The patients treated with ZTI-01 had an overall success rate of 64.7% (119 of 184 patients) compared with 54.5% among patients treated with PIP-TAZ — a treatment difference of 10.2%. Kaye and colleagues wrote that clinical cure rates at the TOC (days 19-21) “were high and similar between treatments,” with 90.8% for ZTI-01 and 91.6% for PIP-TAZ.
The researchers conducted a post-hoc analysis, showing that the overall success rates at TOC in the m-MITT population were 69% for ZTI-01 and 57.3% for PIP-TAZ, for a difference of 11.7%. They wrote that 42.1% of patients treated with ZTI-01 and 32% of patients treated with PIP-TAZ experienced at least one treatment-emergent adverse event, with most adverse events being mild or moderate in severity.
“In ZEUS, IV fosfomycin was effective and noninferior to piperacillin-tazobactam for the treatment of cUTI,” Kaye said. “Once available in the U.S., intravenous fosfomycin will be a good choice for treatment of cUTI, particularly when the infection is caused by resistant gram-negative bacilli.”
Patrick N.A. Harris, BSc, MBBS, MRCP, DTM&H, PhD, an infectious disease physician, medical microbiologist and a National Health and Medical Research Council early career fellow at the University of Queensland Centre for Clinical Research, wrote a commentary related to the study.
“Overall, the ZEUS trial provides some useful data to support the use of IV fosfomycin for treating cUTI or pyelonephritis in stable patients, without features of more severe disease or immune compromise,” Harris wrote. “What we really need now are further trials recruiting patients with [multidrug-resistant] infections who have limited treatment options, where we are most likely to consider using this drug.” – by Bruce Thiel
References:
Harris PNA. Clin Infect Dis. 2019;doi:10.1093/cid/ciz185/5370025.
Kaye KS, et al. Clin Infect Dis. 2019;doi:10.1093/cid/ciz181/5370034.
Disclosures: Harris reports a grant from Shinogi Ltd. outside the submitted work. Kaye reports being a member of the data monitoring committee and a consultant to Zavante Therapeutics Inc. of San Diego, which is now part of Nabriva Therapeutics plc of King of Prussia, Pennsylvania. The study was supported by Zavante Therapeutics. Please see the study for all other authors’ relevant financial disclosures.