Delamanid Resistance: Update and Clinical Management
Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistanc...
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| Vydáno v: | Clinical infectious diseases Ročník 71; číslo 12; s. 3252 |
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| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
15.12.2020
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| ISSN: | 1537-6591, 1537-6591 |
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| Abstract | Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistance emergence, and drug susceptibility testing (DST) for delamanid. Delamanid resistance has already been reported in both in vitro experiments and clinical settings. Although mutations conferring delamanid resistance have been identified in fbiA, fbiB, fbiC, ddn, and fgd1 genes of Mycobacterium tuberculosis, knowledge about the molecular resistance mechanisms is limited, and there remains no standardized DST method. The rapid acquisition of delamanid resistance emphasizes the need for optimal use of new drugs, the need for drug resistance surveillance, and a comprehensive understanding of drug resistance mechanisms. Further studies are necessary to investigate genetic and phenotypic changes that determine clinically relevant delamanid resistance to help develop a rapid delamanid DST. |
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| AbstractList | Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistance emergence, and drug susceptibility testing (DST) for delamanid. Delamanid resistance has already been reported in both in vitro experiments and clinical settings. Although mutations conferring delamanid resistance have been identified in fbiA, fbiB, fbiC, ddn, and fgd1 genes of Mycobacterium tuberculosis, knowledge about the molecular resistance mechanisms is limited, and there remains no standardized DST method. The rapid acquisition of delamanid resistance emphasizes the need for optimal use of new drugs, the need for drug resistance surveillance, and a comprehensive understanding of drug resistance mechanisms. Further studies are necessary to investigate genetic and phenotypic changes that determine clinically relevant delamanid resistance to help develop a rapid delamanid DST. Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistance emergence, and drug susceptibility testing (DST) for delamanid. Delamanid resistance has already been reported in both in vitro experiments and clinical settings. Although mutations conferring delamanid resistance have been identified in fbiA, fbiB, fbiC, ddn, and fgd1 genes of Mycobacterium tuberculosis, knowledge about the molecular resistance mechanisms is limited, and there remains no standardized DST method. The rapid acquisition of delamanid resistance emphasizes the need for optimal use of new drugs, the need for drug resistance surveillance, and a comprehensive understanding of drug resistance mechanisms. Further studies are necessary to investigate genetic and phenotypic changes that determine clinically relevant delamanid resistance to help develop a rapid delamanid DST.Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistance emergence, and drug susceptibility testing (DST) for delamanid. Delamanid resistance has already been reported in both in vitro experiments and clinical settings. Although mutations conferring delamanid resistance have been identified in fbiA, fbiB, fbiC, ddn, and fgd1 genes of Mycobacterium tuberculosis, knowledge about the molecular resistance mechanisms is limited, and there remains no standardized DST method. The rapid acquisition of delamanid resistance emphasizes the need for optimal use of new drugs, the need for drug resistance surveillance, and a comprehensive understanding of drug resistance mechanisms. Further studies are necessary to investigate genetic and phenotypic changes that determine clinically relevant delamanid resistance to help develop a rapid delamanid DST. |
| Author | Bañuls, Anne-Laure Vu, Dinh Hoa Nguyen, Nhung Viet Alffenaar, Jan-Willem C Nguyen, Thi Van Anh Anthony, Richard M Cao, Thi Thu Huyen Nguyen, Van Anh Thi |
| Author_xml | – sequence: 1 givenname: Thi Van Anh surname: Nguyen fullname: Nguyen, Thi Van Anh organization: LMI Drug Resistance in South East Asia, Hanoi, Vietnam – sequence: 2 givenname: Richard M surname: Anthony fullname: Anthony, Richard M organization: Tuberculosis reference laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands – sequence: 3 givenname: Thi Thu Huyen surname: Cao fullname: Cao, Thi Thu Huyen organization: The National Centre of Drug information and Adverse Drug Reaction Monitoring, Hanoi University of Pharmacy, Hanoi, Vietnam – sequence: 4 givenname: Anne-Laure surname: Bañuls fullname: Bañuls, Anne-Laure organization: MIVEGEC, University of Montpellier-IRD-CNRS, Montpellier, France – sequence: 5 givenname: Van Anh Thi surname: Nguyen fullname: Nguyen, Van Anh Thi organization: Laboratory of Tuberculosis, Department of Bacteriology, National Institute of Hygiene and Epidemiology of Vietnam, Hanoi, Vietnam – sequence: 6 givenname: Dinh Hoa surname: Vu fullname: Vu, Dinh Hoa organization: The National Centre of Drug information and Adverse Drug Reaction Monitoring, Hanoi University of Pharmacy, Hanoi, Vietnam – sequence: 7 givenname: Nhung Viet surname: Nguyen fullname: Nguyen, Nhung Viet organization: National Tuberculosis Program, Hanoi, Vietnam – sequence: 8 givenname: Jan-Willem C surname: Alffenaar fullname: Alffenaar, Jan-Willem C organization: Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia |
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| Copyright | The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. |
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| Keywords | delamanid drug susceptibility testing drug resistance pharmacokinetics/pharmacodynamics tuberculosis |
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| SubjectTerms | Antitubercular Agents - pharmacology Antitubercular Agents - therapeutic use Humans Microbial Sensitivity Tests Mycobacterium tuberculosis - genetics Nitroimidazoles - therapeutic use Oxazoles - therapeutic use Tuberculosis, Multidrug-Resistant - drug therapy |
| Title | Delamanid Resistance: Update and Clinical Management |
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