Photo Credit: stefanamer

The following is a summary of “Model-informed identification of optimised dosing strategies for meropenem in critically ill patients receiving SLEDD: an observational study,” published in the April 2025 issue of Infection by Weber et al. 

An increasing number of patients with critical illness receive slow extended daily dialysis (SLEDD) due to their pathophysiology while suffering from sepsis, necessitating effective and safe antibiotic therapy. Although SLEDD reduces meropenem exposure and increases treatment failure risk, effective and safe dosing regimens were unclear.  

Researchers conducted a retrospective study to identify optimized meropenem dosing strategies for patients with critical illness having SLEDD and using population pharmacokinetic (PK) modeling and PK/pharmacodynamic (PD)-based probability of target attainment analysis.  

They monitored clinical data of patients with critical illness and SLEDD receiving meropenem through routine therapeutic drug monitoring. A total of 178 blood samples from 13 patients (a median of 14 samples per patient) were analyzed. A population PK model was developed and used to assess 24 clinically relevant dosing regimens during SLEDD therapy (7-hour on-SLEDD periods q24h) in probability of target attainment (PTA) analyses. The PK/PD target window for minimum meropenem concentration ranged from 8 mg/L (P. aeruginosa; R-breakpoint) to 44.45 mg/L (toxicity threshold).  

The results showed that a 1-compartment PK model with linear elimination and total clearance (CL) split into renal (CL_REN; 45%) and SLEDD-associated (55%) clearance effectively described the SLEDD data. Creatinine clearance (urine-collected; CLCR_urine) was identified as a significant factor for CL_REN. Continuous infusions of 2 g q24h for CLCR_urine 0–25 mL/min and 3 g q24h for CLCR_urine 25–40 mL/min demonstrated the highest PTA, being both effective and safe during SLEDD therapy. A comprehensive dosing nomogram was developed.  

Investigators concluded that the user-friendly dosing nomogram offered a promising approach for optimizing meropenem dosing regimens in patients with critical illness undergoing SLEDD by taking the kidney function into account in clinical settings.

Source: link.springer.com/article/10.1007/s15010-025-02504-0