Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia.
The Discipline of Child and Adolescent Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
J Orthop Res. 2020 Sep;38(9):1883-1894. doi: 10.1002/jor.24615. Epub 2020 Feb 10.
Osteomyelitis and infections associated with orthopedic implants represent a significant burden of disease worldwide. Ceragenins (CSAs) are a relatively new class of small-molecule antimicrobials that target a broad range of Gram-positive and Gram-negative bacteria as well as fungi, viruses, and parasites. This review sets the context of the need for new antimicrobial strategies by cataloging the common pathogens associated with orthopedic infection and highlighting the increasing challenges of managing antibiotic-resistant bacterial strains. It then comparatively describes the antimicrobial properties of CSAs with a focus on the CSA-13 family. More recently developed members of this family such as CSA-90 and CSA-131 may have a particular advantage in an orthopedic setting as they possess secondary pro-osteogenic properties. In this context, we consider several new preclinical studies that demonstrate the utility of CSAs in orthopedic models. Emerging evidence suggests that CSAs are effective against antibiotic-resistant Staphylococcus aureus strains and can prevent the formation of biofilms. There remains considerable scope for developing CSA-based treatments, either as coatings for orthopedic implants or as local or systemic antibiotics to prevent bone infection.
骨髓炎和与骨科植入物相关的感染是全球范围内的重大疾病负担。抗菌肽（CSAs）是一类相对较新的小分子抗菌药物，可靶向广泛的革兰氏阳性和革兰氏阴性细菌以及真菌、病毒和寄生虫。本综述通过列举与骨科感染相关的常见病原体，并强调管理抗生素耐药菌株日益增加的挑战，为新的抗菌策略提供了背景。然后，它比较地描述了 CSAs 的抗菌特性，重点是 CSA-13 家族。该家族中最近开发的成员，如 CSA-90 和 CSA-131，在骨科环境中可能具有特殊优势，因为它们具有促进成骨的次要特性。在这种情况下，我们考虑了几项新的临床前研究，这些研究表明 CSAs 在骨科模型中的实用性。新出现的证据表明，CSAs 对抗生素耐药性金黄色葡萄球菌菌株有效，并可防止生物膜的形成。开发基于 CSA 的治疗方法仍有很大的空间，无论是作为骨科植入物的涂层，还是作为局部或全身抗生素来预防骨感染。
