Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019
Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02753946 (Randomized, Double-Blind, Comparative Study to Evaluate the Safety and Efficacy of ZTI-01 vs Piperacillin/Tazobactam in the Treatment of cUTI/AP Infection in Hospitalized Adults), which is not on this map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized, Double-Blind, Comparative Study to Evaluate the Safety and Efficacy of ZTI-01 vs Piperacillin/Tazobactam in the Treatment of cUTI/AP Infection in Hospitalized Adults
Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- A Meta-Analysis on Clinical Outcomes of Ceftolozane versus Piperacillin in Combination with Tazobactam in Patients with Complicated Urinary Tract Infections.BioMed research international · 2022Pooled it
- Evaluation of the safety profile and intrapulmonary pharmacokinetics of intravenous fosfomycin in healthy adults.Antimicrobial agents and chemotherapy · 2025Trial
- Evaluation of Factors Predictive of Efficacy Among Patients With Complicated Urinary Tract Infection and/or Acute Pyelonephritis.Open forum infectious diseases · 2024Trial
- Trial
- Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.JAMA network open · 2022Trial
- Trial
- Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria-A Subgroup Analysis from the FORTRESS Study.Infectious diseases and therapy · 2026Article
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Active surveillance and risk prediction of piperacillin/tazobactam‑associated hypokalaemia: development and external validation of a clinical nomogram.International journal of clinical pharmacy · 2026Article
- Gram-negative bacterial infection randomized controlled trials (RCTs) in the 21st century: characteristics and evolution.JAC-antimicrobial resistance · 2026Review
- Antibiotic Stewardship in Pediatric Urinary Tract Infections: Current Evidence and Practical Strategies.Antibiotics (Basel, Switzerland) · 2026Review
- Fosfomycin Use in Treating Severe Difficult-to-Treat Gram-Negative Infections-A Comprehensive Review.Antibiotics (Basel, Switzerland) · 2026Review
- A mechanism-based pharmacokinetic/pharmacodynamic analysis of polymyxin B-based combination therapy against carbapenem-resistantAntimicrobial agents and chemotherapy · 2026Article
- Incidence, risk factors, and prediction model of piperacillin/tazobactam-associated hypokalemia in neonates.Therapeutic advances in drug safety · 2026Article
- Prevalence, Antimicrobial Susceptibility, and Molecular Characteristics of Ceftazidime-Avibactam-ResistantInfection and drug resistance · 2026Article
- Intravenous Fosfomycin for Gram-Negative and Gram-Positive Bacterial Infections: A Systematic Review of the Clinical Evidence.Antibiotics (Basel, Switzerland) · 2025Review
- Ampicillin sulbactam impacts serum potassium level comparable to piperacillin tazobactam.Scientific reports · 2025Observational
- Efficacy and Safety of Fosfomycin Disodium in Patients with Bacterial Infections: A Single-Center, Real-Life Clinical Study.Journal of clinical medicine · 2025Article
- Monitoring Plasma Concentrations of Intravenously Administered Fosfomycin to Prevent Drug-Related Adverse Events: A Retrospective Observational Study.Antibiotics (Basel, Switzerland) · 2025Article
- Emerging Concepts for the Treatment of Biofilm-Associated Bone and Joint Infections with IV Fosfomycin: A Literature Review.Microorganisms · 2025Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.
methodsHospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days.
resultsOf 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: -0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19-21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient.
conclusionsZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections. CLINICAL
trial registrationNCT02753946.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.