Department of Microbiology, Institute for Immunology and Immunological Disease, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Sci Rep. 2023 Nov 23;13(1):20631. doi: 10.1038/s41598-023-48001-y.
The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has become a growing concern worldwide, and current treatments involving macrolides (clarithromycin [CLR] or azithromycin), ethambutol, and rifampicin have limited success, highlighting the need for better therapeutic strategies. Recently, oxazolidinone drugs have been identified as novel anti-tuberculosis drugs effective against drug-resistant M. tuberculosis. However, the effects of these drugs against MAC are still controversial due to limited data. Here, we first evaluated the intracellular anti-MAC activities of two oxazolidinone drugs, linezolid (LZD) and delpazolid (DZD), against 10 macrolide-susceptible MAC strains and one macrolide-resistant M. avium strain in murine bone marrow-derived macrophages (BMDMs) and found that both drugs demonstrated similar potential. The synergistic efficacies with CLR were then determined in a chronic progressive MAC-PD murine model by initiating a 4-week treatment at 8 weeks post-infection. Upon assessment of bacterial burdens and inflamed lesions, oxazolidinone drugs exhibited no anti-MAC effect, and there was no significant difference in the synergistic effect of CLR between LZD and DZD. These findings suggest that oxazolidinone drugs inhibit intracellular bacterial growth, even against macrolide-resistant MAC, but their clinical application requires further consideration.
鸟分枝杆菌复合群肺病（MAC-PD）的流行已成为全球日益关注的问题，目前涉及大环内酯类药物（克拉霉素[CLR]或阿奇霉素）、乙胺丁醇和利福平的治疗方法成功率有限，这凸显了需要更好的治疗策略。最近，恶唑烷酮类药物已被确定为新型抗结核药物，对耐药结核分枝杆菌有效。然而，由于数据有限，这些药物对 MAC 的作用仍存在争议。在这里，我们首先在鼠骨髓来源的巨噬细胞（BMDM）中评估了两种恶唑烷酮类药物利奈唑胺（LZD）和德尔帕唑胺（DZD）对 10 株大环内酯类敏感 MAC 株和一株大环内酯类耐药鸟分枝杆菌株的细胞内抗 MAC 活性，发现两种药物均表现出相似的潜力。然后，通过在感染后 8 周开始为期 4 周的治疗，在慢性进行性 MAC-PD 鼠模型中确定与 CLR 的协同疗效。在评估细菌负荷和炎症病变后，恶唑烷酮类药物对 MAC 没有抗作用，并且 LZD 和 DZD 与 CLR 的协同作用没有显著差异。这些发现表明，恶唑烷酮类药物抑制细胞内细菌生长，甚至对大环内酯类耐药 MAC 也有效，但它们的临床应用需要进一步考虑。
