Real-world experience with meropenem/vaborbactam for the treatment of infections caused by ESBL-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae

Abstract

Purpose Real-world experience with meropenem/vaborbactam (M/V) is limited. Our aim is to report a clinical experience of M/V in the treatment of resistant Gram-negative bacilli. Methods This is a prospective observational study including patients hospitalized in the University Hospital of Pisa (March 2021–Jan 2023) with infections by both extended-spectrum β-lactamases (ESBL)-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae (Kp) treated with M/V. The primary outcome measure was clinical success, defined as a composite of survival, resolution of signs and symptoms and absence of microbiological failure at day 30 from infection onset. A multivariable regression analysis was performed to identify factors associated with clinical failure. Odds ratio (OR) with 95% confidence intervals (CI) was calculated. Results A total of 104 patients who received M/V were included: 24/104 (23.1%) infections were caused by ESBL non-hypervirulent Enterobacterales, 17/104 (16.3%) by ESBL-producing hypervirulent Klebsiella pneumoniae (hvKp) and 63/104 (60.6%) by CRE. The most common infections were bloodstream infections, followed by urinary tract infections, hospital-acquired pneumonia, intra-abdominal infections and others. Septic shock occurred in 16/104 (15.4%) patients. Clinical success was achieved in 77% of patients, and 30-day mortality rate was 15.4%. In patients with KPC-producing Kp infections, clinical success and 30-day mortality rates were 82% and 11.5%, respectively. On multivariable analysis, SOFA score (OR 1.32, 95% CI 1.02–1.7, p=0.032) was independently associated with clinical failure, while source control (OR 0.16, 95% CI 0.03–0.89, p=0.036) was protective. Conclusions M/V is a promising therapeutic option against infections caused by difficult-to-treat ESBL-producing Enterobacterales and CR-Kp.

Meropenem/Vaborbactam—A Mechanistic Review for Insight into Future Development of Combinational Therapies

“…Therefore, without combating both classes, a metallo-beta-lactamase inhibitor will most likely be ineffective, as the serine beta-lactamases would still induce resistance. The clinical use of meropenem/vaborbactam is still relatively new; therefore, its clinical efficacy against metallo-beta-lactamases in combination with other inhibitors is still unknown [ 56 ]. Another strategy could be adding a class B specific inhibitor to an already approved combination therapy for serine beta-lactamases, such as meropenem/vaborbactam.…”