Pharmacokinectics of vancomycin and amikacin in the subeschar tissue fluid in patients with severe burn.

The specific aim of this study was to investigate the pharmacokinetic parameters of antibiotics represented by vancomycin and amikacin in the subeschar tissue fluid (STF) in patients with early stage severe burn. Twenty patients were studied: age 30.7+/-8.0 years old, weight 60.6+/-8.4 kg, total burn surface area (TBSA) 68.39+/-17.85%, creatinine clearance (CCr) 95.45+/-23.14 ml/min, mean+/-S.D. Patients received intravenous infusion of 500 mg vancomycin (10 patients) or 400mg amikacin (10 patients) for 60 min at 24h after burn. Subeschar tissue fluid (STF) samples were collected at 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 h at the end of infusion. Concentrations of these antibiotics in the samples were determined by fluorescence polarization immunoassay (FPIA) method. Pharmacokinetic parameters of vancomycin and amikacin were calculated by the use of Program 3P97 and statistical analyses were performed by the use of Program Package SPS S10.0. The concentration-time curves of vancomycin and amikacin in the STF were both fitted in two-compartment model. Pharmacokinetic parameters of vancomycin in the STF were: distribution half-life (t(1)/2alpha)=3.74+/-2.64 h, elimination half-life (t(1)/2beta)=92.18+/-11.73 h, apparent volume of distribution (V(c))=25.64+/-5.68 L, area under the curve (AUC)=1279.42+/-256.12 microg h ml(-1), clearance (CLs)=0.4048+/-0.0788 L h(-1). Pharmacokinetic parameters of amikacin in the STF were: t(1)/2alpha=4.35+/-1.66 h, t(1)/2beta=80.04+/-9.52 h, V(c)=13.17+/-1.32 L, AUC=1802.49+/-285.68 microg h ml(-1), CLs=0.2272+/-0.0383 L h(-1). This study demonstrated significant low clearance, long half life of vancomycin and amikacin in the STF in patients with severe burn compared to the parameters obtained in the serum of normal volunteers in previous studies. Elimination half-lives (t(1)/2beta) of vancomycin and amikacin in the STF of severe burns were 18.75-34.87 times and 28.20-44.78 times longer than those in the serum of normal volunteers, respectively. Concentrations of vancomycin and amikacin in STF at 24h after the end of a single dose infusion was higher than MIC on common pathogenic bacteria. Their effective inhibitory concentration were maintained at least for 24h. There was antibiotic retention in the third space after early and short-term use of potent antibiotics. An antibiotic barrier could form in the STF, and could prevent an invasive bacterial infection from burn wound.