Vancomycin Elution Kinetics of Four Antibiotic Carriers Used in Orthopaedic Surgery: In Vitro Study over 42 Days

Abstract

This study aimed to analyse and compare the vancomycin elution kinetics of four biodegradable, osteoconductive antibiotic carriers used in clinical practice within a 42-day in vitro setting. Carriers A and D already contained vancomycin (1.1 g and 0.247 g), whereas carriers B and C were mixed with vancomycin according to the manufacturer’s recommendations (B: 0.83 g and C: 0.305 g). At nine time points, 50% (4.5 mL) of the elution sample was removed and substituted with the same amount of PBS. Probes were analysed with a kinetic microparticle immunoassay. Time-dependent changes in vancomycin concentrations for each carrier and differences between carriers were analysed. Mean initial antibiotic levels were highest for carrier A (37.5 mg/mL) and lowest for carrier B (5.4 mg/mL). We observed time-dependent, strongly negative linear elution kinetics for carriers A (−0.835; p < 0.001), C (−0.793; p < 0.001), and D (−0.853; p < 0.001). Vancomycin concentrations increased from 48 h to 7 d and dropped thereafter in carriers C and D whilst constantly decreasing at any time point for carrier A. Carrier B showed a shallower decrease. Mean antibiotics levels at 42 d were 1.5 mg/mL, 2.6 mg/mL, 0.1 mg/mL, and 0.1 mg/mL for carriers A, B, C, and D. Differences in mean initial and final vancomycin concentrations for carrier A were significantly larger in comparison to C (p = 0.040). A carrier consisting of allogenic bone chips showed the highest vancomycin-to-carrier ratio and the largest elution over the study period. Whilst vancomycin concentrations were still measurable at 42 days for all carriers, carrier A provided a higher drug-to-carrier ratio and a more consistent antibiotic-releasing profile.