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

Abstract

Background We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of Gram-negative infections (GNI), primarily including carbapenem-resistant Enterobacterales (CRE). Methods This is a real-world, multi-center, retrospective cohort within the United States between 2017-2020. Adult patients who received MEV for ≥ 72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCO) and was examined by multivariable logistic regression analysis (MLR). Results Overall, 126 patients were evaluated from 13 medical centers within ten states. The most common infection source were respiratory tract (38.1%) and intraabdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in four patients; nephrotoxicity (n=2), hepatoxicity (n=1), and rash (n=1). CART-BP between early and delayed treatment was 48 hours (P=0.04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (aOR=0.277, [0.081 – 0.941]). Conclusion Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNI, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCO.

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

“…Authors found that patients appropriately treated within the first 24 h had significantly lower 30-day mortality and in general the time (in hours) from blood culture collection to administration of in vitro active antibiotic treatment was independently associated with outcome [ 92 ]. Consistent findings were observed in a real-world multicenter study with early (within 48 h) MVB administration significantly associated with patient survival [ 93 ]. In bloodstream and even nonbacteremic CRE infections, the Pitt score reliably predicted mortality, with ≥4 confirmed as the best cut-off point [ 94 , 95 ].…”

Comparing the activity of novel antibiotic agents against carbapenem-resistant Enterobacterales clinical isolates

“…As an example, >90% of all KPC-producing isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam. Estimates of the emergence of resistance after clinical exposure of CRE isolates to ceftazidime-avibactam and meropenem-vaborbactam have been described to be ∼20% 13,17-21 and 5%, [21][22][23] respectively. With the inclusion of subsequent isolates, susceptibility percentages would likely be lowered, particularly to ceftazidime-avibactam, in which acquired resistance due to amino acid substitutions in the KPC carbapenemase are not rare events.…”

Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion

“…Moreover, all-cause mortality at day 28 was lower in the MER/VAB group than in the BAT group (15.6% vs. 33.3%; difference −17–7%; 95CI: 44.7–9.3%; p = 0.20). Results from a real-world retrospective multicenter study conducted in the United States showed a 30-day mortality of 18.3% among 126 patients with Gram-negative bacterial infections, including CRE [ 73 ]. Mortality at day 30 was similar in patients with confirmed CRE infections ( n = 99, 19.2%).…”