{"title":"耐药结核病治疗模式的变化:成功、陷阱和未来展望。","authors":"Navisha Dookie, Senamile L Ngema, Rubeshan Perumal, Nikita Naicker, Nesri Padayatchi, Kogieleum Naidoo","doi":"10.1128/cmr.00180-19","DOIUrl":null,"url":null,"abstract":"<p><p>Drug-resistant tuberculosis (DR-TB) remains a global crisis due to the increasing incidence of drug-resistant forms of the disease, gaps in detection and prevention, models of care, and limited treatment options. The DR-TB treatment landscape has evolved over the last 10 years. Recent developments include the remarkable activity demonstrated by the newly approved anti-TB drugs bedaquiline and pretomanid against Mycobacterium tuberculosis. Hence, treatment of DR-TB has drastically evolved with the introduction of the short-course regimen for multidrug-resistant TB (MDR-TB), transitioning to injection-free regimens and the approval of the 6-month short regimens for rifampin-resistant TB and MDR-TB. Moreover, numerous clinical trials are under way with the aim to reduce pill burden and shorten the DR-TB treatment duration. While there have been apparent successes in the field, some challenges remain. These include the ongoing inclusion of high-dose isoniazid in DR-TB regimens despite a lack of evidence for its efficacy and the inclusion of ethambutol and pyrazinamide in the standard short regimen despite known high levels of background resistance to both drugs. Furthermore, antimicrobial heteroresistance, extensive cavitary disease and intracavitary gradients, the emergence of bedaquiline resistance, and the lack of biomarkers to monitor DR-TB treatment response remain serious challenges to the sustained successes. In this review, we outline the impact of the new drugs and regimens on patient treatment outcomes, explore evidence underpinning current practices on regimen selection and duration, reflect on the disappointments and pitfalls in the field, and highlight key areas that require continued efforts toward improving treatment approaches and rapid biomarkers for monitoring treatment response.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":null,"pages":null},"PeriodicalIF":19.0000,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769521/pdf/cmr.00180-19.pdf","citationCount":"2","resultStr":"{\"title\":\"The Changing Paradigm of Drug-Resistant Tuberculosis Treatment: Successes, Pitfalls, and Future Perspectives.\",\"authors\":\"Navisha Dookie, Senamile L Ngema, Rubeshan Perumal, Nikita Naicker, Nesri Padayatchi, Kogieleum Naidoo\",\"doi\":\"10.1128/cmr.00180-19\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Drug-resistant tuberculosis (DR-TB) remains a global crisis due to the increasing incidence of drug-resistant forms of the disease, gaps in detection and prevention, models of care, and limited treatment options. The DR-TB treatment landscape has evolved over the last 10 years. Recent developments include the remarkable activity demonstrated by the newly approved anti-TB drugs bedaquiline and pretomanid against Mycobacterium tuberculosis. Hence, treatment of DR-TB has drastically evolved with the introduction of the short-course regimen for multidrug-resistant TB (MDR-TB), transitioning to injection-free regimens and the approval of the 6-month short regimens for rifampin-resistant TB and MDR-TB. Moreover, numerous clinical trials are under way with the aim to reduce pill burden and shorten the DR-TB treatment duration. While there have been apparent successes in the field, some challenges remain. These include the ongoing inclusion of high-dose isoniazid in DR-TB regimens despite a lack of evidence for its efficacy and the inclusion of ethambutol and pyrazinamide in the standard short regimen despite known high levels of background resistance to both drugs. Furthermore, antimicrobial heteroresistance, extensive cavitary disease and intracavitary gradients, the emergence of bedaquiline resistance, and the lack of biomarkers to monitor DR-TB treatment response remain serious challenges to the sustained successes. In this review, we outline the impact of the new drugs and regimens on patient treatment outcomes, explore evidence underpinning current practices on regimen selection and duration, reflect on the disappointments and pitfalls in the field, and highlight key areas that require continued efforts toward improving treatment approaches and rapid biomarkers for monitoring treatment response.</p>\",\"PeriodicalId\":10378,\"journal\":{\"name\":\"Clinical Microbiology Reviews\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":19.0000,\"publicationDate\":\"2022-12-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769521/pdf/cmr.00180-19.pdf\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Microbiology Reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1128/cmr.00180-19\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/10/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Microbiology Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/cmr.00180-19","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/10/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
The Changing Paradigm of Drug-Resistant Tuberculosis Treatment: Successes, Pitfalls, and Future Perspectives.
Drug-resistant tuberculosis (DR-TB) remains a global crisis due to the increasing incidence of drug-resistant forms of the disease, gaps in detection and prevention, models of care, and limited treatment options. The DR-TB treatment landscape has evolved over the last 10 years. Recent developments include the remarkable activity demonstrated by the newly approved anti-TB drugs bedaquiline and pretomanid against Mycobacterium tuberculosis. Hence, treatment of DR-TB has drastically evolved with the introduction of the short-course regimen for multidrug-resistant TB (MDR-TB), transitioning to injection-free regimens and the approval of the 6-month short regimens for rifampin-resistant TB and MDR-TB. Moreover, numerous clinical trials are under way with the aim to reduce pill burden and shorten the DR-TB treatment duration. While there have been apparent successes in the field, some challenges remain. These include the ongoing inclusion of high-dose isoniazid in DR-TB regimens despite a lack of evidence for its efficacy and the inclusion of ethambutol and pyrazinamide in the standard short regimen despite known high levels of background resistance to both drugs. Furthermore, antimicrobial heteroresistance, extensive cavitary disease and intracavitary gradients, the emergence of bedaquiline resistance, and the lack of biomarkers to monitor DR-TB treatment response remain serious challenges to the sustained successes. In this review, we outline the impact of the new drugs and regimens on patient treatment outcomes, explore evidence underpinning current practices on regimen selection and duration, reflect on the disappointments and pitfalls in the field, and highlight key areas that require continued efforts toward improving treatment approaches and rapid biomarkers for monitoring treatment response.
期刊介绍:
Clinical Microbiology Reviews (CMR) is a journal that primarily focuses on clinical microbiology and immunology.It aims to provide readers with up-to-date information on the latest developments in these fields.CMR also presents the current state of knowledge in clinical microbiology and immunology.Additionally, the journal offers balanced and thought-provoking perspectives on controversial issues in these areas.