Enhancing meropenem therapy in critical care: A retrospective study of PK/PD target attainment and therapeutic drug monitoring.

BACKGROUND: Meropenem is a first-line treatment for severe infections; however, its efficacy is increasingly compromised by drug resistance. This situation underscores the urgent need to optimise dosing strategies and establish precise efficacy evaluation systems.

OBJECTIVES: This study aimed to evaluate the adequacy of the initial meropenem regimen by analysing factors associated with its clinical efficacy in critically ill patients, as well as to define predictive pharmacokinetic/pharmacodynamic (PK/PD) targets.

METHODS: We conducted a retrospective analysis of 205 critically ill patients treated with meropenem. Logistic regression was employed to analyse factors influencing clinical efficacy and bacterial clearance rates, while Cox regression was utilised to assess factors affecting 30-d mortality. Receiver operating characteristic (ROC) analysis was performed to identify PK/PD targets using the first therapeutic drug monitoring (TDM) serum concentrations, and assessed the predictive performance of trough (Cmin) and peak (Cmax) concentrations concerning clinical efficacy.

RESULTS: The clinical effectiveness of meropenem in critically ill patients was found to be 56.6%. Independent risk factors affecting clinical efficacy included Cmin (< 6 mg/L vs. ≥ 6 mg/L), urinary tract infections, tigecycline combination therapy, meropenem-sensitive vs. meropenem-resistant pathogens, sequential organ failure assessment (SOFA) scores (2-5 vs. > 5), and neutrophil counts. Notably, patients receiving prolonged infusion (≥ 2 h) achieved both significantly higher meropenem trough concentrations and better clinical efficacy than those on intermittent infusion. The bacterial clearance rate was 39.0%, which was associated with Cmin (< 8 mg/L vs. ≥ 8 mg/L) and the presence of meropenem-sensitive vs. resistant bacteria. The 30-d mortality rate was 20.0%, linked to age, pulmonary infections, tigecycline combination therapy, surgical history, hospital stay duration, and sequential organ failure assessment (SOFA) scores. Optimal efficacy was achieved with Cmin ≥ 5.3 mg/L and Cmax ≥ 39.4 mg/L, with higher thresholds required for bloodstream infections (Cmin ≥ 7.3 mg/L; Cmax ≥ 49.1 mg/L).

CONCLUSION: Meropenem demonstrates significant efficacy against severe infections caused by sensitive pathogens, particularly in cases of urinary tract infections. We identified that a Cmin of ≥ 5.3 mg/L and a Cmax of ≥ 39.4 mg/L are associated with optimal clinical efficacy. Based on these findings, we propose an initial dosing strategy tailored to renal function and the site of infection. Our results underscore the value of early TDM in identifying patients at risk of suboptimal exposure, which provides a crucial foundation for subsequent dose adjustments. Therefore, to optimise meropenem therapy in critically ill patients, it is crucial to implement a TDM-guided strategy that integrates appropriate dosing, prolonged infusion modalities, and early exposure assessment.