# Therapeutic drug monitoring of daptomycin in a critically ill patient cohort

## TL;DR

This study examines daptomycin levels in critically ill patients and finds that therapeutic drug monitoring leads to more dose increases but does not reduce side effects.

## Contribution

The study provides new insights into daptomycin TDM effectiveness and dose adjustments in critically ill patients.

## Key findings

- Daptomycin trough levels were commonly low in critically ill patients.
- TDM was associated with more frequent dose escalations but no significant reduction in adverse events.
- Patients with TDM had fewer daptomycin-free days alive compared to those without TDM.

## Abstract

Pharmacokinetics of antimicrobial agents are altered in critically ill patients. Therefore, therapeutic drug monitoring (TDM) has gained much attention in recent years. Specifically, the role of TDM for daptomycin, its potential influence on dose adaptations and subsequent daptomycin levels, as well as daptomycin-related side effects is so far unclear in the critical care setting.

This was a retrospective study including critically ill, adult patients from January 2010 to July 2023. No criteria for TDM were predefined and the decision to perform TDM was left to the discretion of the treating physician. The primary outcome was the evaluation of baseline daptomycin trough levels in patients undergoing TDM, and how subsequent levels were affected by potential dose adaptations. Further outcomes included daptomycin-free days alive over 14 days and the occurrence of side effects between patients with and without daptomycin TDM.

Two hundred seventy patients were included. The patient group was heterogeneous regarding elective or emergency admissions and had surgical and medical underlying conditions. Over the ICU stay, median daptomycin trough levels were 9 mg/L (IQR 5.8–16.4 mg/L) and median peak levels were 29. 8 mg/L (IQR 14.8 – 46 mg/L). The first measured daptomycin trough level was too low (<10 mg/L) in 62 patients (54.4%) with TDM. Despite dosage increases in 14 patients (22.6%), median subsequent levels did not increase and were only 7.0 mg/L (IQR 4.8–13.6 mg/L). Patients who underwent TDM experienced significantly more frequent daptomycin dose increases than those who did not (28.8% vs. 13.1%, p = 0.002). Patients with TDM experienced fewer daptomycin-free days alive compared to patients without TDM [5 days (IQR 0–8 days) vs. 10 days (IQR 8–11 days), p < 0.001]. Increases from baseline in creatine kinase levels and eosinophil counts during daptomycin treatment did not differ significantly between patients with and without TDM.

Daptomycin levels might be commonly low in critically ill patients and often appear not to increase after dose adjustments. TDM was associated with more frequent dose escalations and fewer daptomycin-free days, but did not significantly reduce the incidence of adverse events in a large cohort of critically ill patients.