Data Sheet 1_Therapeutic drug monitoring of daptomycin in a critically ill patient cohort.docx

BackgroundPharmacokinetics 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.
MethodsThis 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.
ResultsTwo 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.
ConclusionDaptomycin 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.