Investigating the clinical outcomes of prolonged versus intermittent infusion of meropenem in critically ill pediatric patients: a randomized double-blind single-center study

Abstract

Background

Optimal antibiotic dosing strategies, such as prolonged infusion (PI), are hypothesized to improve clinical outcomes in critically ill patients by maximizing time above the minimum inhibitory concentration. This prospective study aimed to evaluate whether PI of meropenem enhances clinical outcomes and reduces mortality compared to standard intermittent infusion (II) in pediatric patients diagnosed with culture-negative sepsis in the pediatric intensive care unit (PICU).

Methods

A prospective, double-blind, randomized, clinical study was conducted in PICU between May 2019 and November 2019 aimed to evaluate whether PI of meropenem enhances clinical outcomes and reduces mortality in pediatric patients diagnosed with culture-negative sepsis. Eligible patients with culture-negative sepsis were assigned to receive meropenem as either a 3-h PI or a 30-min II administered at a dose of 60 mg/kg/day every 8 h. The primary endpoint was clinical improvement that was defined as a reduction in the pediatric Sequential Organ Failure Assessment (pSOFA) score on the 7th day of meropenem therapy. Secondary outcomes included PICU mortality, C-reactive protein (CRP) level, and length of stay in the PICU.

Results

Baseline characteristics were comparable between the two groups (age, gender, CRP, and pre-treatment pSOFA score). By the 7th day of meropenem therapy, the PI group showed greater clinical improvement, as evidenced by a significantly lower pSOFA score compared to the II group [(median pSOFA score: 1; IQR (4)] versus [(median pSOFA score: 4; IQR: (9.75)] in II group (p = 0.008). The 14-day mortality rate in the PICU was lower among patients receiving PI compared to those treated with II (24.2% vs 57.1%, p < 0.001). CRP showed a greater reduction in the PI compared to the II group (35% vs 105.25%, p = 0.028). Both groups did not differ significantly concerning PICU length of stay (p = 0.104). The ∆pSOFA score showed excellent predictive accuracy (AUC = 0.946) for early treatment response in critically ill pediatric patients, with a cutoff of − 2.5 yielding high sensitivity and specificity. Kaplan–Meier analysis demonstrated a statistically significant difference in survival between the two groups (log-rank p = 0.026), highlighting the impact of treatment strategy on patient outcomes.

Conclusion

PI of meropenem was associated with enhanced clinical improvement and reduced mortality rates in pediatric patients with culture-negative sepsis.