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 vancomycin tissue /vancomycin plasma 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.

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

“…For instance, concentrations in epithelial lining fluid [61] and in soft tissue of diabetic patients are low [62]. Taking into account the good diffusion of linezolid to poorly vascularised tissues, this difference could explain the superiority of linezolid over vancomycin in SSTIs in patients with vascular insufficiency described in a subanalysis of a previous randomised study [63].…”

PK-PD modeling of β-lactam antibiotics: In vitro or in vivo models?

“…However, some studies have demonstrated that infection changes the physiological characteristics of the infected tissue due to the inflammatory process developed by host aiming to eliminate the invasive organism, as observed in soft tissue infections, septic shock, pneumonia or vascular alterations associated to diabetes. [9][10][11][12] In this context, it is not always possible to predict the antimicrobial-free fraction at the site of infection, based on the microdialysis data obtained in healthy tissue or unbound plasma levels.…”

Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review

“…Additionally, increased scrutiny of vancomycin tissue penetration and dosing methods has fostered debate over its role as the cornerstone for serious cSSTIs infections caused by resistant gram-positive organisms (Lipsky et al 2004;Stevens et al 2005;Skhirtladze et al 2006;Mohr and Murray 2007;Deresinski 2007). Vancomycin has long been the workhorse antimicrobial therapy for resistant gram-positive infections; however, increasing resistance in cSSTI pathogens and increasing reports of clinical failures have necessitated the search for alternative agents.…”