| Patients with severe thermal injuries have defective humoral and cellular immunity and are at high risk for serious infections. The loss of the skin barrier and remain of necrotic tissue on the wound provide favorable environment for the growth of bacteria and invasive infection. Optimizing antimicrobial therapy in these patients can be challenging due to physiologic alterations affecting organ functions and drug metabolism. Several antimicrobials, including vancomycin and amikacin, have demonstrated significant pharmacokinetic alterations in severely burned patients. Previous work in burn patient's serum has shown that elimination half-life is decreased for amikacin, and vancomycin; total clearance is increased for vancomycin.The subeschar tissue fluid is a special fluid compartment after severe burn injury .This fluid accumulation is the result of dilation of resistance vessels, increased extravascular osmotic pressure in the burned tissue, and increased microvascular permeability. The contents of this fluid are similar to the contents of plasma, including administered antibiotics. Vancomycin and amikacin are frequently used in the empirical and definitive treatment of infections in burn patients. However, vancomycin and amikacin pharmacokinetics in the subeschar tissue fluid in this population have not been previously described.The primary objective of this study was to characterize the pharmacokinetics of antibiotics represented by vancomycin and amikacin in the STF of patients with severe burn injuries and evaluate the antibiotics retention in the STF in this population.ObjectiveThe specific aim of this study is to characterize the pharmacokinetic parameters of antibiotics represented by vancomycin and amikacin in the subeschar tissue fluid (STF) in patients with early stage severe burn, then investigate the effect of forming an antibiotic barrier could form in the STF to prevent an invasive bacterial infection from burn wound.Methods1. Ten patients with severe burns were enrolled in the study and received intraveneous injection of 500 mg vancomycin evenly within 60 mins at 24 post-burn hours. Total 0.5ml subeschar tissue fluid(STF) was extracted and the concentrations of vancomycin in the STF were determined by Fluorescence polarization immunoassay(FPIA) method at 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 after the first initial dose of vancomycin in 60 mins. Pharmacokinetic parameters of vancomycin were produced by program 3P97 and statistically analyzed by programpackage SPSS10.0.2. Ten patients with severe burns were enrolled in the study and received intraveneous injection of 400 mg amikacin evenly within 60 mins at 24 post-burn hours. Total 0.5ml subeschar tissue fluid(STF) was extracted and the concentrations of amikacin in the STF were determined by Fluorescence polarization immunoassay(FPIA) method at 1, 2, 4, 8, 24, 48, 96, 144, 192, 240 after the first initial dose of amikacin in 60 mins. Pharmacokinetic parameters of amikacin were produced by program 3P97 and statistically analyzed by programpackage SPSS10.0.Results1. After the first initial dose of 500 mg of vancomycin in 60 mins, The STF concentration-time curves of vancomycin were fitted in two compartment model. Pharmacokinetic parameters of vancomycin in the STF were: distribution half-life (t1/2α) = 3.74 +/- 2.64 h, elimination half-life (t1/2β) = 92.18 +/- 11.73 h, apparent volume of distribution (Vc) = 25.64 +/- 5.68 L, area under the curve (AUC) = 1279.42 +/- 256.12μg·h·ml-1, clearance (CLs) = 0.4048 +/- 0.0788 L·h-1. It showed significantly lower clearance, longer elimination half life of vancomycin in the STF of severe burns, when vancomycin is administered in the early stage. Elimination half-life (t1/2β) of vancomycin in the STF of severe burns was 18.75 to 34.87 times longer than that in the serum of normal volunteers.2. After the first initial dose of 400 mg of amikacin in 60 mins, The STF concentration-time curves of amikacin were fitted in two compartment model. Pharmacokinetic parameters of amikacin in the STF were: t1/2α= 4.35 +/- 1.66 h, t1/2β= 80.04 +/- 9.52 h,Vc = 13.17 +/- 1.32 L,AUC = 1802.49 +/- 285.68μg·h·ml-1,CLs = 0.2272 +/- 0.0383 L·h-1. It showed significantly lower clearance, longer elimination half life of amikacin in the STF of severe burns, when amikacin is administered in the early stage. Elimination half-life (t1/2β) of amikacin in the STF of severe burns was 28.20 to 44.78 times longer than that in the serum of normal volunteers.ConclusionConcentrations of vancomycin and amikacin in STF at 24 hours after the end of a single dose infusion was higher than MIC on common pathogenic bacteria. Their effective inhibitory concentration could maintain at least for 24 hours. There was antibiotic retention in the third space after early and short-term use of potent antibiotics. The antibiotic barrier could form in the STF, and could prevent an invasive bacterial infection from burn wound.
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