Pharmacokinetic evaluation of meropenem and vaborbactam for the treatment of urinary tract infection

ABSTRACT

Introduction: Meropenem/vaborbactam (M/V) represents the first carbapenem and β-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, β-lactamase inhibitor with a high affinity for serine β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex.

Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed.

Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.

KEYWORDS:

• Carbapenem-resistant Enterobacteriaceae
• complicated urinary tract infection
• Klebsiella pneumoniae carbapenemase
• meropenem
• pyelonephritis
• vaborbactam

Box 1. Drug summary.

Declaration of interest

L Danziger reports consultancy work for The Medicines Company. KA Rodvold reports research funding and consultancy work for The Medicines Company and Melinta Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper is not funded.