Impact of prolonged versus intermittent infusion of meropenem on mortality and clinical outcomes in patients with severe infection: A systematic review and meta-analysis.
Summary
Across 14 studies (n=1,698), prolonged meropenem infusion reduced all-cause mortality and improved clinical response and microbiologic eradication versus intermittent dosing, with no difference in ICU or hospital length of stay. Benefits were most evident in lower-severity patients (APACHE II <20).
Key Findings
- Prolonged infusion reduced mortality versus intermittent dosing (RR 0.81; 95% CI 0.68–0.98).
- Clinical improvement (RR 1.35; 95% CI 1.11–1.64) and microbiologic eradication (RR 1.19; 95% CI 1.08–1.32) favored prolonged infusion.
- No significant differences in ICU or hospital length of stay; benefits more pronounced in APACHE II <20.
Clinical Implications
Consider prolonged infusion protocols for meropenem, particularly in lower-severity patients, integrated with antimicrobial stewardship and potential therapeutic drug monitoring to optimize time above MIC.
Why It Matters
Provides quantitative clinical support for PK/PD-based carbapenem dosing strategies, addressing a long-standing critical care question with evidence of mortality benefit.
Limitations
- Mix of RCTs and observational studies may introduce residual confounding.
- Heterogeneous dosing regimens and patient populations; limited LOS effects despite mortality benefit.
Future Directions
Large, CONSORT-compliant RCTs with standardized prolonged-infusion protocols and TDM to verify mortality effects across severity strata and pathogens.
Study Information
- Study Type
- Systematic Review/Meta-analysis
- Research Domain
- Treatment
- Evidence Level
- I - PROSPERO-registered meta-analysis of RCTs and observational studies on meropenem infusion strategies
- Study Design
- OTHER