Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection

Autor: Juan Pablo Horcajada, Michael N. Dudley, Elizabeth Alexander, Susan C Bleasdale, Evangelos J. Giamarellos-Bourboulis, Olga Lomovskaya, Olexiy S. Sagan, Tanaya Bhowmick, Ventsislav Stoev, Erik Chorvat, Valerii Zaitsev, Jeffery Loutit, Claudia Murta, Petru Octavian Dragoescu, Elena Fedosiuk, Symeon Metallidis, David E. Griffith, Viktor Stus, Mohamed Bidair, Karen Fusaro, Jose A. Vazquez, Yaroslav V Sarychev, Elizabeth E. Morgan, Keith S Kaye
Rok vydání: 2018
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
030106 microbiology
Population
Penicillanic Acid
Urine
law.invention
03 medical and health sciences
Randomized controlled trial
Levofloxacin
law
Internal medicine
polycyclic compounds
Clinical endpoint
Humans
Medicine
education
Adverse effect
Original Investigation
Aged
Piperacillin
education.field_of_study
Intention-to-treat analysis
Pyelonephritis
business.industry
Meropenem
General Medicine
biochemical phenomena
metabolism
and nutrition
Middle Aged
bacterial infections and mycoses
Boronic Acids
Anti-Bacterial Agents
Intention to Treat Analysis
Clinical trial
Drug Combinations
Piperacillin
Tazobactam Drug Combination
Acute Disease
Practice Guidelines as Topic
Urinary Tract Infections
Piperacillin/tazobactam
bacteria
Female
Thienamycins
business
medicine.drug
Zdroj: JAMA. 319:788
ISSN: 0098-7484
DOI: 10.1001/jama.2018.0438
Popis: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.clinicaltrials.gov Identifier: NCT02166476.
Databáze: OpenAIRE
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