Infection and Drug Resistance (Jan 2023)
Clinical Evaluation of Meropenem-Vaborbactam Combination for the Treatment of Urinary Tract Infection: Evidence to Date
Abstract
Fischer Herald,1 Rodrigo M Burgos1,2 1Department of Pharmacy Practice, College of Pharmacy, University of Illinois Chicago, Chicago, IL, USA; 2Department of Medicine, College of Medicine, University of Illinois Chicago, Chicago, IL, USACorrespondence: Fischer Herald 833 South Wood Street, Room 164, M/C 886, Chicago, IL, 60612, USA Tel +1 312 996 1654 Fax +1 312 413 1797 Email [email protected]: As antimicrobial resistance continues to grow, one of the biggest threats includes the members of the Enterobacterales order presenting with carbapenem resistance (CRE). Meropenem-vaborbactam, along with other beta-lactam/beta-lactamase agents, has been developed to help combat this growing concern and is currently approved to treat complicated urinary tract infections (cUTI), as well as acute pyelonephritis (AP), in the USA. Vaborbactam is a novel beta-lactamase inhibitor designed specifically to optimize and restore the activity of meropenem against resistant Enterobacterales. Vaborbactam inhibits a number of beta-lactamases, including in vitro activity against extended-spectrum beta-lactamases (ESBL) and the Klebsiella pneumoniae carbapenemase (KPC) group. KPC represents one of the most clinically relevant carbapenemase in the USA, accounting for the majority of carbapenemase-producing CRE. Meropenem-vaborbactam has been studied in the two Phase 3, noninferiority trials, TANGO I and TANGO II. TANGO I compared meropenem-vaborbactam against piperacillin-tazobactam in patients with cUTIs and was found to be noninferior for overall success and microbial eradication. TANGO II expanded to other disease states (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia [HAP/VAP], complicated intra-abdominal infection [cIAI], cUTI/AP) and was found to be noninferior against best available therapy (BAT) with respect to clinical cure at the end of treatment and the test of cure. Meropenem-vaborbactam maintained the established safety profile of meropenem alone, with headache as the most common adverse event in both phase 3 studies. Overall, clinical efficacy has been demonstrated and suggests the use of meropenem-vaborbactam for the treatment of cUTI is an option.Keywords: meropenem, vaborbactam, complicated urinary tract infections, pyelonephritis