耐药结核病患者的利奈唑胺耐受性及其在所有口服较短方案中的未来应用

Muhammad Asif, Zaw Myint
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摘要

利奈唑胺(Lzd)属于恶唑烷酮类药物,是一种用于治疗耐药结核病(DR TB)的改型药物。2019年,世卫组织将Lzd与左氧氟沙星/莫西沙星和贝达喹啉一起列为A类药物,是治疗耐药/耐多药结核病的最有效药物。耐药/耐多药结核病治疗方案应结合至少4种可能有效的药物。Lzd的毒性分布可能在22%至80%之间,最常见的毒性是骨髓抑制和神经病变,这种常见的毒性导致Lzd在耐药/耐多药结核病治疗期间从暂时中断到永久停止。毒性发展的中位时间约为治疗5-6个月,但毒性甚至可能在治疗的前几周发生。利奈唑胺(Lzd)通常剂量600mg OD也用于治疗各种革兰氏阳性感染<28天。利奈唑胺毒性是常见的,但相对容易发现和管理,如果不及早发现和及时中断药物治疗,除完全神经损伤外,是可逆的。利奈唑胺(每日600毫克)也是世卫组织推荐的BPaLM和BPaL方案的一部分,这些方案安全、时间较短、成本低且非常有效,可作为未来的耐药/耐多药结核病治疗。为了确保患者的安全,所有结核病规划必须确保适当的药物不良反应安全、监测和管理机制,将其作为耐药结核病治疗的重要组成部分。
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Linezolid Tolerability in Drug Resistant TB Patients and Its Future use in all Oral Shorter Regimens
Linezolid (Lzd) belongs to group of Oxazolidinones a repurposed drug to treat Drug resistant TB (DR TB). WHO in 2019 placed Lzd in Group A Drugs along with Levofloxacin/Moxifloxacin and Bedaquiline as most effective drugs to treat RR/MDR TB. The RR/MDR TB regimen should be constructed with a combination of at least 4 likely effective drugs. The toxicity profile of Lzd may feature from 22% to 80% and among most common toxicities are myelosuppression and neuropathy and such frequent toxicities lead from temporary interruption to permanent discontinuation of Lzd during RR/MDR TB treatment. The median time to development of toxicity is around 5-6 months of treatment but toxicity may occur even during early weeks of treatment. The Linezolid (Lzd) usual dose of 600 mg OD is also used for <28 days to treat various gram-positive infections. Linezolid toxicity is frequent but relatively easy to detect and manage and is reversible other than complete nerve damage if not detected early and drug interrupted timely. Linezolid (600 mg daily) is also part of WHO recommended BPaLM and BPaL regimens which are safe, shorter, low cost and highly effective as future RR/MDR TB treatment. To ensure safety of patients all TB programs must ensure appropriate adverse drug safety, monitoring and management (DSM) mechanism as essential component of Drug resistance TB treatment.
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