An Update on Existing and Emerging Data for Meropenem-Vaborbactam.

Area of Science:

• Antimicrobial resistance
• Pharmacology
• Infectious diseases

Background:

• Multidrug-resistant gram-negative bacterial infections, particularly carbapenem-resistant Enterobacteriaceae (CRE), pose a significant clinical challenge.
• CRE infections exhibit complex resistance mechanisms, including altered drug structure, efflux pumps, and reduced permeability.
• Vaborbactam, a novel cyclic boronic acid, acts as a potent inhibitor of class A carbapenemases, such as Klebsiella pneumoniae carbapenemase (KPC), when combined with meropenem.

Purpose of the Study:

• To review the available literature on meropenem-vaborbactam.
• To describe its spectrum of activity, dosing, pharmacokinetics, pharmacodynamics, safety, and efficacy.
• To evaluate its role in treating multidrug-resistant gram-negative infections.

Main Methods:

• Literature search using terms meropenem, vaborbactam, RPX7009, and meropenem-vaborbactam.
• Databases searched included PubMed, ClinicalTrials.gov, and published abstracts from 2013 to July 2019.
• Inclusion of abstracts from IDWeek 2019, limited to English-language publications.

Main Results:

• Meropenem-vaborbactam demonstrates activity against key gram-negative pathogens like K. pneumoniae, E. coli, and Enterobacter cloacae complex.
• Phase III trials showed improved clinical success in complicated urinary tract infections (cUTIs) compared to piperacillin-tazobactam and superior clinical cure rates for CRE infections versus best available therapy.
• Adverse events were generally mild to moderate, with low rates of discontinuation.

Conclusions:

• Meropenem-vaborbactam is approved for cUTIs and acute pyelonephritis, with emerging evidence supporting its off-label use for CRE infections.
• The combination therapy offers improved clinical cure and potentially better tolerability than standard treatments.
• Further research, including in vivo cases and postmarketing surveillance, will elucidate its full therapeutic role, especially against non-KPC-producing CRE.