National Cohort of Compassionate Use of Meropenem-Vaborbactam: No Benefit over Meropenem for Pseudomonas aeruginosa.

Abstract

Background: Meropenem-vaborbactam (MEM-VAB) is a novel carbapenem-beta-lactamase-inhibitor combination that demonstrates activity against carbapenem-resistant (CR) Gram-negative bacteria, and more specifically KPC-producers, since vaborbactam is an effective inhibitor of KPC enzymes in vitro. This study aimed to describe the initial uses and efficacy of MEM-VAB for compassionate treatment during the first 21 months following its early access in France.

Method: A national multicenter retrospective study was conducted, including all patients who received at least one dose of MEM-VAB between 20 July 2020, and 5 April 2022. Clinical characteristics and outcomes were collected using a standardized questionnaire. The minimum inhibitory concentration (MIC) of antimicrobials, and complete genome sequencing of bacteria were performed when bacterial isolates were available.

Results: Ultimately, 21 patients from 15 French hospitals were included in the study. The main indication for MEM-VAB treatment was respiratory tract infections (n = 9). The targeted bacteria included Pseudomonas aeruginosa (n = 12), Klebsiella pneumoniae (n = 3), Enterobacter spp (n = 3), Citrobacter freundii (n = 1), Escherichia coli (n = 1), and Burkholderia multivorans (n = 1). Overall, no significant advantage of vaborbactam over meropenem alone was observed across all strains of P. aeruginosa in terms of in vitro susceptibility. However, MEM-VAB demonstrated a notable impact, compared to carbapenem alone, on the MIC for the two KPC-3-producing K. pneumoniae and B. multivorans.

Conclusions: MEM-VAB seems effective as a salvage treatment in compassionate use, but vaborbactam was shown to lack benefits compared to meropenem in treating P. aeruginosa-related infections. Therefore, it is crucial to compare meropenem to MEM-VAB MICs, particularly for P. aeruginosa, before prescribing MEM-VAB.