Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis

Abstract

The impact of decreased serum albumin concentrations on free antibiotic concentrations in non-critically ill patients is poorly described. This study aimed to describe the pharmacokinetics of a high-dose regimen of teicoplanin, a highly protein-bound antibiotic, in non-critically ill patients with hypoalbuminaemia. Ten patients with chronic bone sepsis and decreased serum albumin concentrations (<35g/L) receiving teicoplanin 12mg/kg 12-hourly intravenously for 48h followed by 12mg/kg once daily were enrolled. Surgical debridement was performed on Day 3. Samples of venous blood were collected pre-infusion and post-infusion during the first 4 days of therapy. Total and free teicoplanin concentrations were assayed using validated chromatographic methods. The median serum albumin concentration for the cohort was 18 (IQR 15–24) g/L. After 48h, the median (IQR) free trough (fCmin) and total trough (tCmin) concentrations were 2.90 (2.67–3.47) mg/L and 15.54 (10.28–19.12) mg/L, respectively, although trough concentrations declined thereafter. Clearance of the free concentrations was significantly high relative to the total fraction at 38.6 (IQR 29.9–47.8) L/h and 7.0 (IQR 6.8–9.8) L/h, respectively (P<0.001). Multiple linear regression analysis demonstrated that whereas total teicoplanin concentration did not impact on free concentrations (P=0.174), albumin concentration did (P<0.001). This study confirms the significant impact of hypoalbuminaemia on free concentrations of teicoplanin in non-critically ill patients, similar to that in critically ill patients. Furthermore, the poor correlation with total teicoplanin concentration suggests that therapeutic drug monitoring of free concentrations should be used in these patients.