Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections

Abstract

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa

“…Meropenem-vaborbactam (MEV) is a novel boronic acid beta-lactamase inhibitor (BLI) combined with a well-known carbapenem that exhibits activity against MDR Enterobacterales, including KPC-producing strains [ 6 ]. The US Food and Drug Administration (FDA) approved MEV for the management of complicated urinary tract infections on the basis of the TANGO I trial [ 7 , 8 ]. In TANGO I, MEV was associated with improved overall success (defined as clinical cure or improvement and microbiological eradication) when compared with piperacillin-tazobactam meeting the prespecified margin for noninferiority.…”

“…In another trial, TANGO II, MEV was associated with improved clinical cure, decreased mortality, and decreased adverse events when compared with the best available therapy against a variety of CRE infections [ 9 ]. Since then, MEV has been used in clinical practice at a wider scale and for indications beyond those evaluated in the TANGO I and TANGO II trials [ 8 ]. Noninferiority studies do not optimally address outcomes in specific patient populations where new agents maybe most beneficial [ 10 , 11 ].…”

Escalating antimicrobial resistance among Enterobacteriaceae: focus on carbapenemases

“…Importantly, MEV may be effective even against CRE carrying mutations in KPC genes that substantially reduce the potency of CAZ-AVI but have little effect on MEV 218,219 . In a recent cohort of 40 patients treated with MEV for serious GNB infections (80.0% were CRE), clinical success was achieved in 70.0% 220 . Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively 220 , 221 .…”

An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by Enterobacterales in Critically Ill Adult Patients

“… Trend to lower mortality rate with CAZ-AVI. Meropenem-vaborbactam Wunderink et al, 2018 77 Phase 3, randomized, prospective, multicenter, open-label 47 (32 MER-VAB vs 15 BAT) MER-VAB 2 g/2 g q8h (3h-infusion) 100% target therapy Dose adjustment for renal impairment according to manufacturer’s instruction 14 primary BSI 12 cUTI/AP 4 HAP/VAP 2 cIAI 29 K. pneumoniae 3 E. coli 1 E. cloacae 1 S. marcescens ICU admission 15.6% Immunocompromised 34.4% Clinical cure rate at the end of treatment: 65.6% vs 33.3% (p=0.03) Clinical cure rate at test of cure: 59.4% vs 26.7% (p=0.02) Mortality rate at 28-day: 15.6% vs 33.3% NA Monotherapy with MER-VAB for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT Ackley et al, 2020 78 Retrospective observational cohort, multicenter, comparative 131 (26 MER-VAB vs 105 CAZ-AVI) MER-VAB 2 g/2 g q8h 100% target therapy 12 HAP/VAP (2) 8 cIAI (3) 3 SSTI (1) 1 primary BSI 1 cUTI (1) 1 other (1) () number of secondary BSIs 15 Klebsiella spp 8 Enterobacter spp 3 E. coli 2 Citrobacter spp 1 Serratia spp ICU admission 65.4% Median APACHE II score 27 RRT 4.8% Immunocompromised 15.4% Overall clinical success: 69.2% vs 61.9% Mortality rate at 30-day: 11.5% vs 19.1% Relapse 11.5% No resistance development Similar rates of clinical success between MER-VAB and CAZ-AVI in KPC-producing CRE infections Alosaimy et al, 2020 79 Retrospective observational, multicenter, non-comparative 40 MER-VAB 2 g/2 g q8h 100% target therapy 13 HAP/VAP 11 BSI 8 cUTI 5 cIAI 5 SSTI <...>…”