Introduction: Insulin Dependent Diabetes Mellitus (IDDM) is one of the major risk factors, despite antibiotic prophylaxis, for wound infections after cardiac surgery. Vancomycin is used for the treatment of infections caused by methicillin resistant staphylococcus aureus (MRSA) and for antibiotic prophylaxis. However, it is unknown whether antimicrobial plasma concentrations reflect tissue concentration of vancomycin in IDDM patients. Therefore, we compared vancomycin tissue concentrations of 6 diabetic patients and 6 non-diabetics (ND).
Method: Vancomycin was administered continuously to achieve steadystate plasma concentrations (range 25-30 mg/L). To measure vancomycin tissue concentration we employed the microdialysis technique. Samples from the interstitial space of skeletal muscle were collected using a semipermeable membrane at the tip of a microdialysis probe. Simultaneously, plasma concentrations of vancomycin were evaluated. Samples were analysed by a fluorescence-polarisation immunoassay. Data are presented as medians and ranges. Mann-Whitney U test was used for statistical analysis.
Results: Vancomycin tissue concentrations in IDDM patients (3.6mg/L) were significantly lower compared with ND (11.4 mg/L; P = 0.031). Median vancomycin [tissue]/vancomycin [plasma] concentration ratios in IDDM was 0.1 in contrast to 0.3 in NDs.
Discussion: A vancomycin MIC 90 < 1 mg/L is regarded as good susceptibility of the pathogen. Per definition a vancomycin MIC of >4mg/L by micro-dilution in Mueller-Hilton broth read at 24h is regarded as glycopeptide-intermediate staphylococcus aureus (GISA). Vancomycin tissue concentrations were sufficient in both groups for treatment of infections caused by staphylococcus aureus strains with good susceptibility. However, tissue concentrations in IDDM patients were insufficient for treatment of infections with GISA, whereas, NDs showed adequate tissue concentrations for treatment of these less susceptible strains of staphylococcus aureus.
Conclusion: Our study demonstrated that plasma concentrations derived during a continuous infusion of vancomycin with target levels of 25-30 mg/L do not reflect tissue concentrations in diabetic patients. Insufficient tissue concentration could possibly contribute to the development of antimicrobial resistance.
1 Zacharias A, Habib RH. Factors predisposing to median sternotomy complications. Deep vs. superficial infection. Chest
, 1996; 110
2 Muller M, Schmid R, Georgopoulos A, et al. Application of microdialysis to clinical pharmacokinetics in humans. Clin Pharmacol Ther
3 Wysocki M, Delatour F, Faurisson F, et al. Continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother