Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery

Abstract

Soft tissue infections constitute a serious complication following surgery in diabetic patients and frequently require the administration of vancomycin. However, despite antibiotic treatment, mortality of patients with postoperative infections remains high and might be related to an impaired penetration of anti-infective agents to target tissues. Therefore, the present study was designed to measure vancomycin tissue concentrations in six diabetic and six nondiabetic patients after cardiac surgery. Vancomycin was administered as a continuous intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin concentrations in soft tissues and plasma were measured in all patients during steady state as "therapeutic window" concentrations in plasma by microdialysis on day 8+/-4 after initiation of vancomycin treatment. Vancomycin tissue concentrations in diabetic patients were significantly lower than in nondiabetics (3.7 mg/liter versus 11.9 mg/liter; P=0.002). The median vancomycintissue/vancomycinplasma concentration ratio was 0.1 in diabetic patients and 0.3 in nondiabetics (P=0.002). Our study demonstrated that vancomycin penetration into target tissues is substantially impaired in diabetic patients versus nondiabetics. Insufficient tissue concentrations could therefore possibly contribute to failure of antibiotic treatment and the development of antimicrobial resistance in diabetic patients.

FIG. 1.

Time versus vancomycin concentration profiles for soft tissue after determination of steady-state vancomycin plasma concentrations in diabetic (open squares, n = 6) and nondiabetic (solid squares, n = 6) patients. Values are presented as medians and ranges. The tissue and plasma concentrations were measured at the same time point. For better discrimination, the values for nondiabetics have been shifted.

FIG. 2.

Time versus vancomycin concentration profiles for plasma after determination of steady-state vancomycin plasma concentrations in diabetic (open circles, n = 6) and nondiabetic (solid circles, n = 6) patients. Values are presented as medians and ranges. The tissue and plasma concentrations were measured at the same time point. For better discrimination, the values for nondiabetics have been shifted.

FIG. 3.

Time course of vancomycin_tissue/vancomycin_plasma concentration ratios as a measure of vancomycin penetration into soft tissue in diabetic patients (open squares, n = 6) and nondiabetics (solid squares, n = 6). Values are presented as medians and ranges. The tissue and plasma concentrations were measured at the same time point. For better discrimination, the values for nondiabetics have been shifted.