Impact of prolonged versus intermittent infusion of meropenem on mortality and clinical outcomes in patients with severe infection: A systematic review and meta-analysis.

OBJECTIVES

To compare the clinical outcomes of patients with severe infection treated with prolonged or intermittent infusion of meropenem.

METHODS

PubMed, Embase, and Cochrane Central databases were searched until July 2023. Randomized controlled trials (RCTs) or observational studies comparing prolonged versus intermittent infusion of meropenem were considered eligible. The primary outcomes included all-cause mortality and clinical improvement, while secondary outcomes encompassed hospital and intensive care unit (ICU) stay duration, microbial eradication rate, and adverse events. A meta-analysis was conducted using a random-effects model. The risk of bias of included studies was assessed using the modified JADAD scale for RCTs and the Newcastle-Ottawa Scale for observational studies.

RESULTS

Fourteen studies were included, with a total of 1698 patients. Prolonged infusion of meropenem was associated with a significantly lower mortality rate compared to intermittent infusion (RR = 0.81, 95 % CI: 0.68-0.98). It also significantly improved clinical improvement rates (RR = 1.35, 95 % CI: 1.11-1.64) and microbial eradication rates (RR = 1.19, 95 % CI: 1.08-1.32). There were no statistically significant differences in ICU length of stay or hospital length of stay. Subgroup analyses showed that prolonged infusion was significantly associated with lower mortality and better clinical improvement rates in patients with an APACHE II score <20.

CONCLUSIONS

Prolonged infusion of meropenem is more effective than intermittent infusion in reducing mortality, improving clinical outcomes, and enhancing microbial eradication, without increasing adverse events. These benefits are particularly evident in patients with lower disease severity (APACHE II < 20), emphasizing the importance of patient stratification in optimizing treatment strategies.

REGISTRATION

This systematic review and meta-analysis is registered with PROSPERO (number: CRD42023445360).