Effectiveness and safety of meropenem–vaborbactam versus ceftazidime–avibactam in multidrug-resistant Gram-negative infections: a systematic review and meta-analysis with trial sequential analysis

Antimicrobial resistance driven by multidrug-resistant (MDR) Gram-negative pathogens poses a major global threat, contributing to substantial morbidity and mortality. Novel β-lactam/β-lactamase inhibitor combinations, particularly meropenem-vaborbactam (M/V) and ceftazidime-avibactam (C/A), have expanded therapeutic options; however, their comparative efficacy and safety remain uncertain. This meta-analysis compared M/V and C/A in adult patients with MDR Gram-negative infections. MEDLINE, Embase, and Cochrane Central were searched for studies evaluating M/V versus C/A in hospitalized adults. Outcomes included all-cause mortality, clinical cure, and microbiological recurrence; safety was assessed qualitatively. Data were synthesized using Review Manager, with trial sequential analysis (TSA) applied to minimize random error. Five retrospective cohort studies (three full articles and two conference abstracts) comprising 3,280 patients were included, of whom 577 received M/V and 2,703 received C/A. Populations predominantly consisted of older adults aged 57-70 years, with respiratory tract infections being most common. Pooled analyses demonstrated no statistically significant differences between M/V compared to C/A in all-cause mortality (Odds ratio [OR] 0.87; 95% CI 0.69-1.11; <i>P</i> = 0.26; I² = 16%), clinical cure (OR 1.41; 95% CI 0.66-3.03; <i>P</i> = 0.37; I² = 55%), and microbiological recurrence (OR 0.67; 95% CI 0.32-1.40; <i>P</i> = 0.29; I² = 0%). Qualitative synthesis indicated comparable tolerability. TSA for mortality demonstrated insufficient evidence for definitive conclusions. M/V showed no statistically significant difference over C/A; therefore, selection should be guided judiciously based on clinical context. Further studies are needed to define the optimal role of each agent within antimicrobial stewardship frameworks.