Gualano Gina, Capone Susanna, Matteelli Alberto, Palmieri Fabrizio
Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases L. Spallanzani , Rome.
Department of Infectious and Tropical Diseases, WHO Collaborating Centre for TB/HIV and TB Elimination, University of Brescia , Italy.
Infect Dis Rep. 2016 Jun 24;8(2):6569. doi: 10.4081/idr.2016.6569.
Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials. Delamanid is the first drug of the nitroimidazole class to enter clinical practice. Similarly to bedaquiline results of phase IIb studies showed increased sputum-culture conversion at 2 months and better final treatment outcomes in patients with MDR-TB. Among repurposed drugs linezolid and carbapenems may represent a valuable drug to treat cases of MDR and extensively drug-resistant TB. The recommended regimen for MDR-TB is the combination of at least four drugs to which M. tuberculosis is likely to be susceptible for the duration of 20 months. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Clinical phase III trials on new regimen are ongoing that could prove transformative against MDR-TB, by being shorter (six months), simpler (an all-oral regimen) and safer than current standard therapy. It is fundamental that the adoption of the new drugs is done responsibly to avoid inappropriate use. Concentration of in-patient MDR-TB treatment in specialized centers could be considered in countries with low numbers of cases in order to provide appropriate clinical case management and to prevent emergence of drug resistance.
耐多药结核病（MDR-TB）病例的治疗具有挑战性，因为它依赖于二线药物，这些药物的效力低于用于药物敏感结核病临床管理的药物，且毒性更大。此外，与药物敏感疾病相比，MDR-TB的治疗效果通常较差，这凸显了对新药的需求。五十多年来首次有两种新型抗结核药物获批上市。贝达喹啉是首个同类二芳基喹啉化合物，在IIb期试验中显示24周时培养物持续转阴。德拉马尼是首个进入临床实践的硝基咪唑类药物。与贝达喹啉类似，IIb期研究结果显示，MDR-TB患者在2个月时痰培养转阴率提高，最终治疗效果更好。在重新利用的药物中，利奈唑胺和碳青霉烯类可能是治疗MDR和广泛耐药结核病病例的有价值药物。MDR-TB的推荐治疗方案是至少四种结核分枝杆菌可能敏感的药物联合使用，疗程为20个月。根据疗效、安全性和成本，通过五组逐步选择过程来选择药物。目前正在进行新治疗方案的III期临床试验，该方案可能被证明对MDR-TB具有变革性，因为它比当前标准疗法更短（六个月）、更简单（全口服方案）且更安全。负责任地采用新药以避免不当使用至关重要。在病例数较少的国家，可以考虑将MDR-TB住院治疗集中在专门中心，以便提供适当的临床病例管理并防止耐药性的出现。
