National Cohort of Compassionate Use of Meropenem–Vaborbactam: No Benefit over Meropenem for <i>Pseudomonas aeruginosa</i>

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 (<i>n</i> = 9). The targeted bacteria included <i>Pseudomonas aeruginosa</i> (<i>n</i> = 12), <i>Klebsiella pneumoniae</i> (<i>n</i> = 3), <i>Enterobacter spp</i> (<i>n</i> = 3), <i>Citrobacter freundii</i> (<i>n</i> = 1), <i>Escherichia coli</i> (<i>n</i> = 1), and <i>Burkholderia multivorans</i> (<i>n</i> = 1). Overall, no significant advantage of vaborbactam over meropenem alone was observed across all strains of <i>P. aeruginosa</i> 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 <i>K. pneumoniae</i> and <i>B. multivorans</i>. Conclusions: MEM-VAB seems effective as a salvage treatment in compassionate use, but vaborbactam was shown to lack benefits compared to meropenem in treating <i>P. aeruginosa</i>-related infections. Therefore, it is crucial to compare meropenem to MEM-VAB MICs, particularly for <i>P. aeruginosa</i>, before prescribing MEM-VAB.