On August 29^th 2017, the FDA approved meropenem-vaborbactam (Vabomere) for adults with complicated urinary tract infections (cUTI). Vabomere is a fixed-dose combination of the carbapenem-class drug known as meropenem, along with the novel beta-lactamase inhibitor, vaborbactam. Vaborbactam is a potent inhibitor of KPC beta-lactamases, as well as other beta-lactamases (specifically CTX-M, SHV, TEM, P99, MIR, and FOX). The approval of Vabomere follows the approval Ceftazidime–Avibactam back in February of 2015 for the treatment of cUTI and complicated intra-abdominal infection (cIAI), when used in combination with metronidazole.

Data supporting the FDA approval of Vabomere came from the TANGO-1 study. TANGO-1 was a multi-center, randomized, double blinded, double dummy phase-3 study to evaluate the efficacy, safety and tolerability of meropenem-vaborbactam vs piperacillin-tazobactam in the treatment of cUTI in adults. The trial enrolled 550 adults who were randomized to either receive meropenem- vaborbactam or piperacillin-tazobactam, each for up to 10 days. After a minimum of 5 days of IV therapy, patients who met protocol-defined criteria of improvement were transitioned to oral levofloxacin. Meropenem-vaborbactam was found to be stastically superior to piperacillin-tazobactam, with an overall success of 98.4% vs 94.0% (95% CI: 0.7–9.1%). Drug related adverse events (15.1 % vs 12.8%) and rates of discontinuation (2.6 % vs 5.1%) were not stastically significantly different between the two treatment groups.

In addition to TANGO-1, the TANGO-2 study was a phase 3 study that randomized patients with suspected carbapenem-resistant Enterobactericiae (CRE) infections to meropenem–vaborbactam or best available therapy. Potential infectious syndromes evaluated included cUTI, hospital acquired pneumonia/ventilator acquired pneumonia (HAP/VAP), cIAI, and bacteremia. The study was discontinued early after interim analysis of 74 patients showed that, for efficacy, statistically-significant differences favored meropenem-vaborbactam over best available therapy for clinical cure. Mortality rates and renal adverse rates were also lower among patients treated with meropenem-vaborbactam. Of note, patients will continue to be enrolled into an amended, single-arm study protocol for treatment with meropenem-vaborbactam at selected sites.

The safety and tolerability of Vabomere was also assessed in a phase one randomized, placebo-controlled, double-blind, sequential single- and multiple-ascending-dose study of 80 healthy adult subjects by Griffith et al. No subjects discontinued the study due to adverse events (AEs), and no serious AEs (SAEs) were observed. Mild lethargy was noted as the only unique AE, and was primarily reported with the higher doses of vaborbactam. In testing of pharmacokinetic properties of combination meropenem–vaborbactam in 26 healthy adults by Wenzler et al., one subject had to discontinue the administration of meropenem-varobactam due to chest discomfort, dizziness, and dyspnea.

Vabomere does have some potential holes in its coverage however. Similar to ceftazidime-avibactam, it lacks inhibition of class B MBLs (the most notable of these is NDM-1). When tested against 4500 Gram-negative clinical isolates from 11 New York City hospitals, Lapuebla and colleagues found that Vabomere inhibited growth of 98.5% of multi-drug-resistant CRE isolates. However, Vabomere had reduced activity against two KPC-producing K. pneumoniae isolates, which had reduced OmpK35 and OmpK36 expression. Notably, vaborbactam did not improve the activity of meropenem against A. baumannii and P. aeruginosa, due to alternative mechanisms of drug resistance including alternation in porin channels and drug efflux.

With increasing rates of resistance developing with the use of ceftazidime–avibactam (“You use it- you lose it”), Vabomere is a welcomed addition in the arsenal for the treatment of ESBL and CRE infections.

It was previously destined to be called Carbavance but seems that the manufactures had a change of heart and went with Vabomere. What other ridiculous antibiotics names do you have soft spot for? What do you think of Vabomere vs Carbavance.

I personally think we have a dearth of antibiotics which start with the letter V, so my vote goes to Vabomere. Both seem like some ridiculous dark lord nemesis names. But maybe that’s what’s needed to combat the rising rates of ESBL and MDR organisms.

-Ahmed Babiker, MBBS; 1st Year ID Fellow at Pitt