Efficacy and safety of continuous versus intermittent meropenem infusion for sepsis treatment: A systematic review and meta-analysis

Background: The optimal administration strategy for meropenem in sepsis remains debated, with conflicting evidence regarding continuous (CI) versus intermittent infusion (II). This meta-analysis evaluates comparative efficacy and safety. Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science until April 2025 for randomized controlled trials (RCTs) and observational studies comparing CI and II meropenem in adult sepsis patients. Primary outcomes included mortality and clinical cure rates; secondary outcomes comprised microbiological eradication, length of stay (LOS), and adverse events. Data were pooled using random-effects models (I²≥50%) or fixed-effects models (I²<50%). Results: Seven studies (3,452 patients) were included. CI demonstrated a 40% reduction in mortality (RR 0.60, 95% CI 0.39–0.94, p=0.02; I²=0%) and doubled clinical cure rates (RR 2.09, 95% CI 1.51–2.89, p<0.00001; I²=44%) compared to II. Microbiological eradication was significantly higher with CI (RR 2.40, 95% CI 1.58–3.64, p<0.0001; I²=0%). Subgroup analyses revealed consistent benefits across study designs, with no increased risk of nephrotoxicity (RR 1.05, p=0.70) or neurotoxicity (RR 0.92, p=0.82). ICU LOS did not differ significantly overall but was shorter in septic shock subgroups (MD −1.5 days, p=0.02). Conclusions: Continuous meropenem infusion significantly improves survival, clinical cure, and microbiological outcomes in sepsis without additional safety concerns. These findings support CI as a preferred administration strategy, particularly for severe cases. Protocol standardization and further RCTs to optimize dosing are warranted.