ALLIUM
Trial question
Is cefepime/enmetazobactam superior to piperacillin/tazobactam in patients with complicated UTI or acute pyelonephritis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
55.0% female
45.0% male
N = 1034
1034 patients (568 female, 466 male)
Inclusion criteria: adult patients with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by Gram-negative urinary pathogens
Key exclusion criteria: urine culture with gram-positive primary pathogen; hypersensitivity or allergic reaction to trial drugs; weight > 180 kg; life expectancy < 6-week study period
Interventions
N=516 cefepime/enmetazobactam (cefepime 2 g/enmetazobactam 0.5 g given by 2-hour infusion every 8 hours for 7 days)
N=518 piperacillin/tazobactam (piperacillin 4 g/tazobactam 0.5 g given by 2-hour infusion every 8 hours for 7 days)
Primary outcome
Overall treatment success at day 14
79.1
58.9
79.1 %
59.3 %
39.5 %
19.8 %
0.0 %
Cefepime/enmetazobactam
Piperacillin/tazobactam
Significant increase ▲
NNT = 4
Significant increase in overall treatment success at day 14 (79.1% vs. 58.9%; AD 21.2%, 95% CI 14.3 to 27.9)
Secondary outcomes
No significant difference in clinical cure at day 14 (92.5% vs. 88.9%; AD 3.5%, 95% CI -1 to 8)
Significant increase in microbiological eradication at day 14 (82.9% vs. 64.9%; AD 19%, 95% CI 12.3 to 25.4)
Significant increase in overall success at day 21 (68.4% vs. 58.9%; AD 10.7%, 95% CI 3.4 to 17.8)
Safety outcomes
No significant difference in treatment-emergent adverse events.
Conclusion
In adult patients with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by Gram-negative urinary pathogens, cefepime/enmetazobactam was superior to piperacillin/tazobactam with respect to overall treatment success at day 14.
Reference
Keith S Kaye, Adam Belley, Philip Barth et al. Effect of Cefepime / Enmetazobactam vs Piperacillin / Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial. JAMA. 2022 Oct 4;328(13):1304-1314.
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