Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Department of Orthopaedics, Southern Medical University Nanfang Hospital, Guangzhou, 510515, Guangdong, China.
Sci Rep. 2021 Jan 14;11(1):1446. doi: 10.1038/s41598-020-80764-6.
This study investigated the efficacy of a biphasic synthetic β-tricalcium phosphate/calcium sulfate (β-TCP/CS) bone graft substitute for compatibility with vancomycin (V) in combination with tobramycin (T) or gentamicin (G) evidenced by the duration of potency and the prevention and killing efficacies of P. aeruginosa (PAO1) and S. aureus (SAP231) biofilms in in vitro assays. Antibiotic loaded β-TCP/CS beads were compared with antibiotic loaded beads formed from a well characterized synthetic calcium sulfate (CS) bone void filler. β-TCP/CS antibiotic loaded showed antimicrobial potency against PAO1 in a repeated Kirby-Bauer like zone of inhibition assay for 6 days compared to 8 days for CS. However, both bead types showed potency against SAP231 for 40 days. Both formulations loaded with V + T completely prevented biofilm formation (CFU below detection limits) for the 3 days of the experiment with daily fresh inoculum challenges (P < 0.001). In addition, both antibiotic loaded materials and antibiotic combinations significantly reduced the bioburden of pre-grown biofilms by between 3 and 5 logs (P < 0.001) with V + G performing slightly better against PAO1 than V + T. Our data, combined with previous data on osteogenesis suggest that antibiotic loaded β-TCP/CS may have potential to stimulate osteogenesis through acting as a scaffold as well as simultaneously protecting against biofilm infection. Future in vivo experiments and clinical investigations are warranted to more comprehensively evaluate the use of β-TCP/CS in the management of orthopaedic infections.
本研究通过体外试验评估了双相合成β-磷酸三钙/硫酸钙（β-TCP/CS）骨移植替代物与万古霉素（V）联合妥布霉素（T）或庆大霉素（G）的疗效，以评估其对铜绿假单胞菌（PAO1）和金黄色葡萄球菌（SAP231）生物膜的效能持续时间、预防和杀灭效果。比较了载抗生素的β-TCP/CS 珠与由特性明确的合成硫酸钙（CS）骨空隙填充剂形成的载抗生素珠。与 CS 相比，β-TCP/CS 抗生素载药珠在重复的 Kirby-Bauer 抑菌圈试验中对 PAO1 的抗菌效力持续 6 天，而 CS 则持续 8 天。然而，两种珠类型对 SAP231 的效力均持续 40 天。两种制剂均加载 V+T 可完全防止生物膜形成（CFU 低于检测限），在 3 天的实验中每天用新鲜接种物进行挑战（P<0.001）。此外，两种载抗生素材料和抗生素组合均能显著降低预生长生物膜的生物负荷 3 至 5 个对数级（P<0.001），V+G 对 PAO1 的效果略优于 V+T。我们的数据结合之前关于成骨作用的研究数据表明，载抗生素的β-TCP/CS 可能具有通过充当支架同时防止生物膜感染来刺激成骨的潜力。需要进行未来的体内实验和临床研究，以更全面地评估在骨科感染管理中使用β-TCP/CS。
