Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat; however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rifampicin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.

大约 40% 的慢性和复发性骨髓炎治疗失败的部分原因是细菌的持续存在。已知金黄色葡萄球菌是人类骨髓炎的主要病原体，通过表型适应性小菌落变异 (SCV) 和细胞内储库（包括主要骨细胞类型中的储库）的形成而持续存在，从而降低对抗生素的敏感性。金黄色葡萄球菌的细胞内感染很难治疗；然而，没有针对这些骨髓炎感染的循证临床指南。我们对文献进行了系统回顾，以确定所有抗生素对细胞内金黄色葡萄球菌的疗效与骨髓炎有关，包括蛋白质生物合成抑制剂（林可酰胺类、链阳菌素类、大环内酯类、恶唑烷类、四环素类、夫西地酸类和氨基糖苷类）、酶抑制剂（氟喹诺酮类和安沙霉素类）和细胞壁抑制剂（β-内酰胺类抑制剂、糖肽类、磷霉素和脂肽类） ). 在 PubMed 和 Embase 数据库中筛选了与细胞内金黄色葡萄球菌相关的文章infections 比较多种抗生素或单一抗生素与另一种治疗的有效性，这导致 34 篇全文文章符合纳入标准。这些研究的综合结果在很大程度上是不确定的，很可能是由于使用了过多的方法。因此，本文探讨了所采用模型背景下的报告发现以及增进理解的可能解决方案。虽然利福平、奥利万星、利奈唑胺、莫西沙星和苯唑西林被确定为最有效的潜在细胞内治疗药物，但这些药物的科学证据仍然相对薄弱。我们提倡进行更标准化的研究，以确定抗生素在金黄色葡萄球菌中的细胞内有效性骨髓炎，以改善治疗和患者预后。