Mortality Outcomes associated with Meropenem Front-Loading Dose in Critically Ill Septic Patients with Acute Kidney Injury

Abstract

Introduction:
In acute kidney injury (AKI), increased volume of distribution (Vd) may reduce therapeutic drug concentrations. Appropriate antimicrobial dosing is crucial to maximise microbial killing. Meropenem front-loading dose, defined as administering the full dose unchanged during the first 24 hours. This study aimed to evaluate the clinical outcomes such as survival, Intensive Care Units (ICU) / hospital length of stay (LOS) and duration of mechanical ventilation as well as the safety profile of meropenem front-loading dose in critically ill septic patients with AKI.
Methods:
A prospective, multicenter, observational study was conducted across 15 ICU in Malaysia. Adult patients diagnosed with sepsis who received at least 72 hours of meropenem treatment, with or without a front-loading dose, between May 2017 and May 2018 were included. Patients were monitored throughout their ICU stay, and all data were collected using a standardized data collection form. Data were analysed descriptively and univariate analysis was performed to assess associations and differences between groups.
Results:
A total of 78 patients were treated with meropenem. On average, the patients were 53.1 (SD=15.1) years of age, predominantly male (n=50, 64.1%) and admitted from medical unit (n=41, 52.5%). Majority of patients were treated with meropenem empirically (n=54, 69.2%). The most prevalent infection types were community-acquired pneumonia (n=13, 16.7%) and hospital acquired/ventilator-associated pneumonia (n=11, 14.1%). Klebsiella pneumoniae (n=10, 12.8%) and Pseudomonas aeruginosa (n=4, 5.1%) were the most common bacterial infections encountered. Although statistically insignificant, patients treated with meropenem front-loading dose had lower mortality than patients treated without meropenem front-loading dose (38.7% vs 44.7%, P=0.601). Similarly, the meropenem front-loading dose group showed shorter ICU/hospital LOS and duration of mechanical ventilation. No adverse effects related to meropenem were reported.
Conclusion:
The study highlighted the potential impact of meropenem front-loading dose in reducing ICU mortality, ICU/hospital LOS, and duration of mechanical ventilation, although these differences were not statistically significant. Optimizing antimicrobial dosing in critically ill patients with AKI remains crucial, and further research is needed to confirm its clinical benefits.