Meropenem-vaborbactam non-inferior to piperacillin-tazobactam for complicated urinary tract infections: The TANGO I trial

1. In this randomized controlled trial, meropenem-vaborbactam was found to be non-inferior to piperacillin-tazobactam for treating complicated urinary tract infections (UTIs).

2. The rate of adverse events were similar between groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: As carbapenemases become more prevalent among organisms that cause complicated Urinary Tract Infections (UTIs), the need for antibiotic therapies that cover these organisms also becomes increasingly important. Vaborbactam, a cyclic boronic acid-based beta-lactamase inhibitor, coupled to meropenum is an emerging antibacterial strategy against these organisms, but it is unclear if this regimen is as effective as current therapies. In this randomized controlled trial, meropenum-vaborbactim was found to be non-inferior to piperacillin-tazobactam in treating patients with complicated UTIs. In addition, the rate of adverse effects was found to be similar between groups.

Overall, this study does suggest that vaborbactam-meropenum is a suitable alternative to piperacillin-tazobactam for complicated UTIs, but it remains unclear if this is a suitable strategy against carbapenemase-resistant bacterial infections. Though the authors point out that studying these resistant infections would be difficult because piperacillin-tazobactam would not be an ethical control, a study evaluating vaborbactam-meropenum against these resistant pathogens would be essential to differentiate this treatment from others in terms of clinical usefulness.

Click to read the study, published in JAMA

Relevant Reading: Antibiotic Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae: Systematic Evaluation of the Available Evidence

In-Depth [randomized control trial]: The Targeting Antibiotic Non-Susceptible Gram-Negative Organisms (TANGO I) study is a phase 3, multicenter, randomized, double-blind trial that enrolled 545 (93% completion rate) adults with complicated UTI from Nov 2014 to April 2016 in 60 sites across 17 countries. Eligible patients were randomized 1:1 using a computer to receive meropenam-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. Once a patient had successfully finished 15 or more doses, they could be switched to oral levofloxacin if they met criteria for improvement, to complete 10 days total treatment (intravenous + oral). Clinical outcome assessment was performed on day 3 of therapy, end of intravenous treatment, end of total treatment, and at 7 and 14-days after end of treatment. The primary endpoint was overall success (clinical cure or improvement and microbial eradication) at the end of intravenous treatment. European Medicines Agency (EMA) criteria was used to check for microbial eradication. Overall, success occurred in 189 of 192 (98.2%) patients on meropenem-vaborbactam vs 171 of 182 (94.0%) (difference 4.5%; CI₉₅ 0.7% to 9.1%; p < 0.001 for noninferiority). Microbial eradiaction occurred in 128 of 192 (66.7%) with meropenam-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference 5.9%; CI₉₅ -4.2 to 16.0%]; p < 0.001 for noninferiority). The rate of adverse side effects were similar in each group.

Image: PD

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