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重症患者或肠道功能不全患者的结核肠外治疗方案:简要综述与方案建议

Tuberculosis parenteral therapeutic regimens for critical patients or non-functional intestinal tract: Brief review and proposal of protocol.

作者信息

Martins Antonio Camargo, Garcia Márcia Teixeira, Resende Mariângela Ribeiro

机构信息

Ambulatório de Referência Regional de TB-MDR/MNT do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil; Infectologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil; Rede Brasileira de Pesquisa em Tuberculose (REDE-TB), Rio de Janeiro, RJ, Brasil; Programa de Tuberculose de Indaiatuba, Secretaria de Saúde de Indaiatuba, Indaiatuba, SP, Brasil; Saúde Coletiva, Faculdade de Medicina, Centro Universitário Max Planck (UNIMAX), Indaiatuba, SP, Brasil.

Ambulatório de Referência Regional de TB-MDR/MNT do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil; Infectologia, Hospital Municipal Dr Mário Gatti, Campinas, SP, Brasil; Infectologia, Faculdade de Medicina, Faculdade São Leopoldo Mandic, Campinas, SP, Brasil.

出版信息

Braz J Infect Dis. 2025 May-Jun;29(3):104526. doi: 10.1016/j.bjid.2025.104526. Epub 2025 Apr 7.

DOI:10.1016/j.bjid.2025.104526
PMID:40194474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12001114/
Abstract

Standard anti-tuberculosis regimens (Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol [RHZE]) remain challenging for critically ill patients and those with a non-functioning gastrointestinal tract. In Brazil, these challenges are amplified by the lack of Intravenous (IV) rifampicin, isoniazid, and ethambutol, which often results in suboptimal outcomes. This brief communication synthesized evidence on parenteral therapies and proposed a structured, five-step protocol for critically ill patients unable to receive oral drugs. A narrative review of the guidelines and key studies was also conducted. IV formulations of RHZE are approved in only some countries and are not available everywhere. Alternative IV drug classes, such as fluoroquinolones, aminoglycosides, carbapenems, and oxazolidinones, can address malabsorption or intolerance to oral RHZE. However, no standardized regimen exists for this population. Our five-step protocol advises: (1) Characterizing each TB case, (2) determining IV necessity, (3) Consulting specialized TB services, (4) Designing a safe and effective regimen, and (5) Re-evaluating therapy for transition to oral treatment. Given the morbidity and mortality from severe TB in Intensive Care Units (ICU), a formalized approach is essential. Further research and policy initiatives regarding IV first-line drugs are crucial to improve treatment outcomes in this vulnerable group. This strategy unifies practice across diverse clinical settings.

摘要

标准抗结核治疗方案(利福平、异烟肼、吡嗪酰胺和乙胺丁醇[RHZE])对于重症患者和胃肠道功能不全的患者而言仍然具有挑战性。在巴西,由于缺乏静脉注射用的利福平、异烟肼和乙胺丁醇,这些挑战更加严峻,这往往导致治疗效果欠佳。本简短通讯综合了关于肠外治疗的证据,并为无法口服药物的重症患者提出了一个结构化的五步方案。还对相关指南和关键研究进行了叙述性综述。RHZE的静脉制剂仅在一些国家获得批准,并非随处可得。替代的静脉用药类别,如氟喹诺酮类、氨基糖苷类、碳青霉烯类和恶唑烷酮类,可以解决对口服RHZE的吸收不良或不耐受问题。然而,针对这一人群尚无标准化治疗方案。我们的五步方案建议:(1)对每例结核病病例进行特征描述,(2)确定静脉用药的必要性,(3)咨询专业结核病服务机构,(4)设计安全有效的治疗方案,以及(5)重新评估向口服治疗过渡的治疗方案。鉴于重症监护病房(ICU)中严重结核病的发病率和死亡率,一种规范化的方法至关重要。关于静脉注射一线药物的进一步研究和政策举措对于改善这一弱势群体的治疗效果至关重要。这一策略统一了不同临床环境下的治疗实践。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54c8/12001114/7beffc8056b5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54c8/12001114/7beffc8056b5/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54c8/12001114/7beffc8056b5/gr1.jpg

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本文引用的文献

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Bull World Health Organ. 2024 Aug 1;102(8):600-607. doi: 10.2471/BLT.24.291881. Epub 2024 May 28.
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New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?用于治疗结核病的新型恶唑烷酮类药物:新的治疗方法即将出现?
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A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis.一项 IIb 期、开放性、随机对照剂量范围多中心试验,旨在评估不同剂量 delpazolid 联合贝达喹啉、德拉马尼、莫西沙星治疗新诊断、无并发症、痰涂片阳性、药物敏感的肺结核成人患者的安全性、耐受性、药代动力学和暴露-反应关系。
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