Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae
Lindsay A Petty,1 Oryan Henig,1 Twisha S Patel,2 Jason M Pogue,3 Keith S Kaye1 1Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, USA; 2Department of Pharmacy Services, University of Michigan Hospitals and Health Centers, Ann Arbo...
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doaj-f3b0527125f24f7faf831b8ec18db4ac2020-11-24T23:31:19ZengDove Medical PressInfection and Drug Resistance1178-69732018-09-01Volume 111461147240574Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant EnterobacteriaceaePetty LAHenig OPatel TSPogue JMKaye KSLindsay A Petty,1 Oryan Henig,1 Twisha S Patel,2 Jason M Pogue,3 Keith S Kaye1 1Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, USA; 2Department of Pharmacy Services, University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA; 3Department of Pharmacy Services, Sinai-Grace Hospital, Detroit Medical Center, Detroit, MI, USA Abstract: There has been a worldwide increase in infections caused by drug-resistant Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae (CRE). Meropenem-vaborbactam, a carbapenem antibiotic and novel boronic acid-based beta-lactamase inhibitor, is a fixed-dose combination product with potent in vitro activity against Enterobacteriaceae that are Klebsiella pneumoniae carbapenemase producers. Meropenem-vaborbactam has been studied in two Phase III trials, Targeting Antibiotic Non-susceptible Gram-negative Organisms (TANGO)-I and TANGO-II. TANGO-I was a multicenter, international Phase III, randomized, double-blind, double-dummy, active-control trial to evaluate the efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infection, including acute pyelonephritis. Among patients with complicated urinary tract infection and growth of a baseline pathogen, meropenem-vaborbactam was determined to be superior to piperacillin-tazobactam based on the composite outcome of symptom improvement or resolution and microbial eradication at the end of intravenous therapy. TANGO-II was a multicenter, international, Phase III, randomized, prospective, open-label, comparative trial to evaluate the efficacy and safety of meropenem-vaborbactam vs best available therapy for CRE infections. Treatment with meropenem-vaborbactam resulted in higher rates of clinical cure at the end of therapy (64.3%vs 33.3%, P=0.04). Additionally, 28-day all-cause mortality was 17.9% in the meropenem-vaborbactam group compared to 33.3% in the best available therapy group, a relative risk reduction of 46.5% (P=0.03). In addition to meropenem-vaborbactam, three other agents with activity against CRE are in late-stage development: imipenem-relebactam, plazomicin, and cefiderocol. The data from Phase II and III studies will help to further define the role of these agents. Overall, the recent approval of meropenem-vaborbactam and the active pipeline for other agents with broad Gram-negative activity are encouraging developments on the CRE therapeutic front. Keywords: meropenem, vaborbactam, carbapenemase, CRE, UTI, KPChttps://www.dovepress.com/overview-of-meropenem-vaborbactam-and-newer-antimicrobial-agents-for-t-peer-reviewed-article-IDRmeropenemvaborbactamcarbapenemaseCREUTIKPC |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Petty LA Henig O Patel TS Pogue JM Kaye KS |
spellingShingle |
Petty LA Henig O Patel TS Pogue JM Kaye KS Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae Infection and Drug Resistance meropenem vaborbactam carbapenemase CRE UTI KPC |
author_facet |
Petty LA Henig O Patel TS Pogue JM Kaye KS |
author_sort |
Petty LA |
title |
Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae |
title_short |
Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae |
title_full |
Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae |
title_fullStr |
Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae |
title_full_unstemmed |
Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae |
title_sort |
overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant enterobacteriaceae |
publisher |
Dove Medical Press |
series |
Infection and Drug Resistance |
issn |
1178-6973 |
publishDate |
2018-09-01 |
description |
Lindsay A Petty,1 Oryan Henig,1 Twisha S Patel,2 Jason M Pogue,3 Keith S Kaye1 1Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, USA; 2Department of Pharmacy Services, University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA; 3Department of Pharmacy Services, Sinai-Grace Hospital, Detroit Medical Center, Detroit, MI, USA Abstract: There has been a worldwide increase in infections caused by drug-resistant Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae (CRE). Meropenem-vaborbactam, a carbapenem antibiotic and novel boronic acid-based beta-lactamase inhibitor, is a fixed-dose combination product with potent in vitro activity against Enterobacteriaceae that are Klebsiella pneumoniae carbapenemase producers. Meropenem-vaborbactam has been studied in two Phase III trials, Targeting Antibiotic Non-susceptible Gram-negative Organisms (TANGO)-I and TANGO-II. TANGO-I was a multicenter, international Phase III, randomized, double-blind, double-dummy, active-control trial to evaluate the efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infection, including acute pyelonephritis. Among patients with complicated urinary tract infection and growth of a baseline pathogen, meropenem-vaborbactam was determined to be superior to piperacillin-tazobactam based on the composite outcome of symptom improvement or resolution and microbial eradication at the end of intravenous therapy. TANGO-II was a multicenter, international, Phase III, randomized, prospective, open-label, comparative trial to evaluate the efficacy and safety of meropenem-vaborbactam vs best available therapy for CRE infections. Treatment with meropenem-vaborbactam resulted in higher rates of clinical cure at the end of therapy (64.3%vs 33.3%, P=0.04). Additionally, 28-day all-cause mortality was 17.9% in the meropenem-vaborbactam group compared to 33.3% in the best available therapy group, a relative risk reduction of 46.5% (P=0.03). In addition to meropenem-vaborbactam, three other agents with activity against CRE are in late-stage development: imipenem-relebactam, plazomicin, and cefiderocol. The data from Phase II and III studies will help to further define the role of these agents. Overall, the recent approval of meropenem-vaborbactam and the active pipeline for other agents with broad Gram-negative activity are encouraging developments on the CRE therapeutic front. Keywords: meropenem, vaborbactam, carbapenemase, CRE, UTI, KPC |
topic |
meropenem vaborbactam carbapenemase CRE UTI KPC |
url |
https://www.dovepress.com/overview-of-meropenem-vaborbactam-and-newer-antimicrobial-agents-for-t-peer-reviewed-article-IDR |
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