Bone penetrance of locally administered vancomycin powder in a rat femur fracture model |
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| Affiliation: | 1. University of Utah Department of Orthopaedic Surgery, Salt Lake City, UT, USA;2. University of Utah Undergraduate Program, Salt Lake City, UT, USA;3. VA Salt Lake City Health Care System, Salt Lake City, UT, USA;1. Department of Orthopaedic Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, China;2. Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig Maximilians University, Munich, Germany;1. Leibniz Universität Hannover, Institute of Mechatronic Systems, 30167 Hannover, Germany;2. Trauma Department, Hannover Medical School, 30625 Hannover, Germany;1. Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Foundation, United States;2. National Farm Medicine Center, Marshfield Clinic Research Foundation, United States;3. Division of Research, Essentia Institute of Rural Health, United States;4. Department of Medicine and Public Health, University of Washington and Veterans Administration Puget Sound Health Care System, United States;1. Department of Orthopaedics and Trauma, Royal Adelaide Hospital, Adelaide, Australia;2. Department of Orthopaedics and Trauma Surgery, Lucerne Cantonal Hospital, Lucerne, Switzerland;3. Discipline of Orthopaedics, The University of Adelaide, Adelaide, Australia |
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| Abstract: | IntroductionLocally delivered, crystalline vancomycin has been suggested as a potential prophylactic measure against the development of deep and superficial surgical site infection. Clinical expectations regarding the duration and peak of drug concentration in local tissues following administration are unknown. Our goal was to develop concentration vs time curves for locally administered vancomycin powder in a high-energy, open femur fracture rat model in local tissues and to compare that data to two well performed similar, systemic administration studies.MethodsAfter approval for animal research, 24 adult Sprague-Dawley rats sustained closed, midshaft femoral fracture under anesthesia. Fractures were caused via blunt guillotine with 750 g metal rod dropped 50 cm. Injured hindlimbs were surgically opened at fracture to simulate open injury and stabilized using 0.054 Kirschner wires. Vancomycin powder was administered using weight-based protocol (goal: 25 mg/kg). Rats were sacrificed in groups of 4 at 4, 8, 24, 48, 72, 96 h. Samples harvested included rat-tail venous blood prior to sacrifice, and femoral bone and anterior thigh soft-tissue were harvested post-mortem. High Performance Liquid Chromatography (HPLC) was performed on all samples.ResultsConcentration vs. time curves demonstrated that the surrounding soft-tissues demonstrated highest maximum concentration (1.5 mg vancomycin/g muscle). Bone reached maximum average of 199 μg vancomycin/g femur: approximately 13% of maximal soft-tissue absorption. Plasma reached maximum concentration of 1.8 μg/mL plasma. All peaks at t = 4 h. Within 48 h, average muscle vancomycin concentration dropped to 3 μg/g muscle (0.2% maximum muscle concentration) and the average bone concentration dropped to 1.9 μg/g femur (0.9% maximum bone concentration). Vancomycin was undetectable on all samples at 96 h. Comparison to classical animal studies suggest local delivery to bone exceeds that of IV dosing for approximately 48 h and may peak near concentrations of 102 multiples.ConclusionsLocally administered vancomycin provides drug delivery in excess of IV dosing for approximately 48 h after intervention. Exponential decay demonstrates rapid removal of drug to near undetectable levels in bone, plasma, and local soft tissue thereafter in a rat model. Local delivery may generate concentrations exceeding that achievable by steady state systemic dosing for 48 h. |
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| Keywords: | Vancomycin Antibiotic Local delivery Injury model Rat study Basic science |
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