Higashihira Shota, Simpson Stefanie J, Morita Akira, Suryavanshi Joash R, Arnold Christopher J, Natoli Roman M, Greenfield Edward M
Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Bone Joint Res. 2024 Mar 4;13(3):101-109. doi: 10.1302/2046-3758.133.BJR-2023-0038.R2.
Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone.
-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs).
Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms.
Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection.
生物膜感染是骨科领域最具挑战性的并发症之一，因为生物膜内的细菌受到宿主免疫系统和许多抗生素的保护。哈利新（Halicin）对许多浮游细菌具有广谱活性，先前的研究表明，哈利新对在聚苯乙烯或聚丙烯基质上生长的生物膜也有效。然而，许多抗生素的有效性会根据生物膜生长的骨科相关基质的不同而发生显著变化。因此，本研究评估了哈利新对在钛合金、钴铬合金、超高分子量聚乙烯（UHMWPE）、失活肌肉或失活骨上生长的较不成熟和较成熟生物膜的活性。
将Xen36生物膜在各种基质上培养24小时或7天。将生物膜与不同浓度的哈利新或万古霉素孵育，然后在无抗生素的情况下使其恢复生长。通过菌落形成单位（CFU）计数和刃天青还原试验确定最小生物膜清除浓度（MBEC），并与浮游菌最小抑菌浓度（MIC）进行比较。
与万古霉素相比，哈利新对在所有测试的骨科相关基质上生长的生物膜继续表现出显著更强的抗菌活性（p < /em>0.01），万古霉素是一种已知受生物膜成熟度影响的抗生素。例如，哈利新对较不成熟和较成熟生物膜的MBEC比其MIC高10倍至40倍。相比之下，万古霉素对较不成熟生物膜的MBEC比其MIC高50倍至200倍；对较成熟生物膜的MBEC比其MIC高100倍至400倍。
哈利新是一种有前景的抗生素，应在骨科感染动物模型中进行测试。
