Background: Daptomycin dose is adjusted to body weight and renal function and is usually not guided by therapeutic drug monitoring (TDM). Daptomycin plasma concentration measurement was established at our institution in January 2009 and is now increasingly being used. The aim of this study was to describe and characterize variability in daptomycin exposure during routine clinical therapy.
Methods: We collected daptomycin plasma concentrations that were measured at our institution during the period January 2009-July 2012. Additional clinical and demographic data and their association with daptomycin exposure was tested by a multilevel linear regression analysis.
Results: A total of 332 daptomycin plasma concentrations were determined in 86 patients. 66% (n=218) of all determinations were trough concentrations (Cmin) and 34% (n=114) were peak concentrations (Cmax). Cmin ranged 2-68mg/L (median 16.7mg/L) and Cmax 20-236mg/L (median 66.2mg/L). A significant positive association of total dose, albumin, creatinine, and a significant negative association of dose interval and intermittent haemodialysis with Cmin was found in the regression analysis. Total dose and Intensive Care Unit (ICU)_-stay was significantly associated with Cmax (P<0.05). However, only 28% (P<0.005) of Cmin variability and 8% (P=0.08) of Cmax variability was explained by the factors included in the analysis.
Conclusion: Daptomycin plasma concentrations are often unpredictable as shown by highly variable drug exposure that is only partially explained by dose administered and underlying renal function.