Factors affecting a variability of serum vancomycin concentrations in clinical practice

Abstract

This study assessed vancomycin concentrations in standard dosing regimens in a routine clinical practice and determined factors affecting their variability. Patients with normal renal function more often experienced low trough serum vancomycin concentrations (5.7 [3.9; 8.4] mcg/ml). The median vancomycin concentration in patients receiving renal replacement therapy (RRT) was 8 [4; 14] mcg/ml; in patients with renal failure not receiving RRT – 12.5 [7.2; 16.4] mcg/ml. The sub-therapeutic trough serum vancomycin concentrations (<5 mcg/ml) were observed significantly more frequently in the ICU patients with normal renal function (p<0.05). The lower vancomycin concentrations correlated with the greater volume of fluid replacement therapy (Spearman r = -0.354; р=0.038). The increases in vancomycin concentrations to potentially toxic levels were due to untimely dosing regimen adjustment in patients with changing renal function, especially, in patients with renal failure not receiving RRT (Spearman r = -0.39; р<0.05). The higher vancomycin concentrations were also observed in patients with normal and reduced renal function not receiving RRT, but receiving concomitant therapy with inotropic agents (p=0.068), loop diuretics (p<0.05), and non-steroidal anti-inflammatory drugs (p<0.05). Albumin levels, residual renal function in patients receiving RRT as well as a type of membranes used for RRT did not significantly affect trough serum vancomycin concentrations. This study showed that sub-therapeutic vancomycin concentrations occur frequently in clinical practice, especially, in ICU patients. Overall, there is a great inter-patient variability in vancomycin concentrations which requires therapeutic drug monitoring to adjust dosing regimen.