The FDA has approved meropenem/vaborbactam (Vabomere™; (MER/VAB), Rempex Pharmaceuticals) for the treatment of complicated urinary tract infections (cUTIs) in patients 18 years and older, including pyelonephritis caused by specific bacteria.
MER/VAB contains a carbapenem that inhibits bacterial cell wall synthesis and a beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases such as Klebsiella pneumonia carbapenemase (KPC). The spectrum of activity includes Escherichia coli, Klebsiella pneumonia, and Entereobacter cloacae species complex. MER/VAB is supplied as 2 grams: meropenem 1 g/vaborbactam 1 g.
The efficacy of MER/VAB was evaluated in a Phase 3 comparator-controlled clinical trial of 545 patients with cUTI, including pyelonephritis. MER/VAB 4 gram (meropenem 2 g/vaborbactam 2 g) IV every 8 hours was compared with piperacillin/tazobactam (PIP/TAZ) 4.5 g IV every 8 hours. After at least 15 doses of IV therapy, patients were switched to oral levofloxacin for a total of 10 days of therapy, unless baseline bacteremia was present (14 days total therapy). Patient demographics and baseline characteristics were considered balanced between the treatment groups.
The primary outcome was achievement of overall success in patients in the microbiological modified intent-to-treat (m-MITT) population, defined as clinical cure or improvement, and microbiological response defined as eradication. Both clinical and microbiological responses were assessed again at the test of cure (TOC) visit approximately 7 days after therapy completion.
Approximately 98% of patients treated with MER/VAB achieved overall success compared with approximately 94% of patients treated with PIP/TAZ. At the TOC visit, approximately 77% of patients treated with MER/VAB and 73% of patients treated with PIP/TAZ had achieved clinical cure and microbiological eradication.
The safety of MER/VAB was evaluated in the aforementioned Phase 3 trial. Treatment was discontinued due to adverse effects in 2.9% of patients receiving MER/VAB. The most frequently reported adverse effects associated with MER/VAB included headache, phlebitis/infusion site reactions, and diarrhea. Hypersensitivity reactions occurred in 1.8% of patients in this trial, and thus MER/VAB is contraindicated in patients with a known anaphylactic reaction to beta-lactam antibiotics. Rarely, seizures and other adverse CNS effects, Clostridium difficile-associated diarrhea, and increased risk of breakthrough seizures due to a drug interaction with valproic acid have also been reported with MER/VAB.
Clinical trials have shown there is no significant difference in safety or effectiveness when using MER/VAB in the geriatric population. Safety and effectiveness has not yet been established in patients younger than 18 years of age. There is insufficient human data to determine an associated risk with fetal harm or miscarriage; however, fetal malformation was observed in studies with rabbits treated with vaborbactam.
Administration of MER/VAB is 4 g (meropenem 2 g/vaborbactam 2 g) every 8 hours IV over 3 hours for up to 14 days for the treatment of cUTI. Renal dose adjustments are recommended for patients with an estimated glomerular filtration rate (eGFR) of less than 50 mL/min/1.73 m2 and are as follows: eGFR between 30-49 mL/min/1.73m2 administer MER/VAB 2 g (meropenem 1 g/vaborbactam 1 g) every 8 hours, eGFR between 15-29 mL/min/1.73 m2 administer MER/VAB 2 g (meropenem 1 g/vaborbactam 1 g) every 12 hours, and for eGFR of less than 15 mL/min/1.73 m2 administer MER/VAB 1 g (meropenem 0.5 g/vaborbactam 0.5 g) every 12 hours. There are no hepatic dose adjustments for MER/VAB.
1. Vabomere [package insert] Parsippany, NJ: The Medicines Company; 2017
2. ClinicalTrials.gov. Identified NCT02166476, Efficacy, safety, tolerability of meropenem-vaborbactam compared to piperacillin-tazobactam in complicated urinary tract infections (cUTIs), including acute pyelonephritis (AP), in adults. Available at: https://clinicaltrials.gov/ct2/show/results/NCT02166476. Accessed on Dec. 5, 2017.