The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/16252 |
Resumo: | NIH |
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Ahidjo, Bintou A.Maiga, Mariama C.Ihms, Elizabeth A.Maiga, MamoudouOrdonez, Alvaro A.Cheung, Laurene S.Beck, SarahAndrade, Bruno de BezerrilJain, SanjayBishai, William R.2016-10-17T12:32:58Z2016-10-17T12:32:58Z2016AHIDJO, B. A. et al. The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis. JCI Insight, v. 1, n. 14, p. e86017, 2016.2379-3708https://www.arca.fiocruz.br/handle/icict/1625210.1172/jci.insight.86017NIHJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA / Howard Hughes Medical Institute. Chevy Chase, Maryland, USAJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA / Howard Hughes Medical Institute. Chevy Chase, Maryland, USAJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA / Johns Hopkins University School of Medicine. Molecular and Comparative Pathobiology. Baltimore,MD, USAJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA / Université des Sciences, des Techniques et des Technologies de Bamako. Bamako, MaliJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA / Johns Hopkins University School of Medicine. Center for Infection and Inflammation Imaging Research. Baltimore, MD, USA / Johns Hopkins University School of Medicine. Department of Pediatrics. Baltimore, MD, USAJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USAJohns Hopkins University School of Medicine. Molecular and Comparative Pathobiology. Baltimore, MD, USAFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. 7Unidade de Medicina Investigativa, Laboratório Integrado de Microbiologia e Imunorregulação. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para a Investigação da Tuberculose. Salvador, BA, BrasilJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA / Johns Hopkins University School of Medicine. Center for Infection and Inflammation Imaging Research. Baltimore, MD, USA / Johns Hopkins University School of Medicine. Department of Pediatrics. Baltimore, MD, USAJohns Hopkins University School of Medicine. Center for Tuberculosis Research. Baltimore, MD, USA / Howard Hughes Medical Institute. Chevy Chase, Maryland, USAPirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). Because tuberculosis (TB) is characterized by granulomatous inflammation in conjunction with parenchymal destruction and replacement fibrosis, we sought to determine whether the addition of pirfenidone as an adjunctive, host-directed therapy provides a beneficial effect during antimicrobial treatment of TB. We hypothesized that pirfenidone's antiinflammatory and antifibrotic properties would reduce inflammatory lung damage and increase antimicrobial drug penetration in granulomas to accelerate treatment response. The effectiveness of adjunctive pirfenidone during TB drug therapy was evaluated using a murine model of chronic TB. Mice treated with standard therapy 2HRZ/4HR (H, isoniazid; R, rifampin; and Z, pyrazinamide) were compared with 2 alternative regimens containing pirfenidone (Pf) (2HRZPf/4HRPf and 2HRZPf/4HR). Contrary to our hypothesis, adjunctive pirfenidone use leads to reduced bacterial clearance and increased relapse rates. This treatment failure is closely associated with the emergence of isoniazid monoresistant bacilli, increased cavitation, and significant lung pathology. While antifibrotic agents may eventually be used as part of adjunctive host-directed therapy of TB, this study clearly demonstrates that caution must be exercised. Moreover, as pirfenidone becomes more widely used in clinical practice, increased patient monitoring would be required in endemic TB settings.engdesconhecidaTuberculoseGranulomaFibrose pulmonar idiopáticaInfecçãoPirazinamidaTratamentoIdiopathic Pulmonary FibrosisAnti-Infective AgentsTuberculosisPyrazinamideTreatment FailureGranulomaThe antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/16252/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAhidjo BA The antifibrotic....pdfAhidjo BA The 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| dc.title.pt_BR.fl_str_mv |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis |
| title |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis |
| spellingShingle |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis Ahidjo, Bintou A. Tuberculose Granuloma Fibrose pulmonar idiopática Infecção Pirazinamida Tratamento Idiopathic Pulmonary Fibrosis Anti-Infective Agents Tuberculosis Pyrazinamide Treatment Failure Granuloma |
| title_short |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis |
| title_full |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis |
| title_fullStr |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis |
| title_full_unstemmed |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis |
| title_sort |
The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis |
| author |
Ahidjo, Bintou A. |
| author_facet |
Ahidjo, Bintou A. Maiga, Mariama C. Ihms, Elizabeth A. Maiga, Mamoudou Ordonez, Alvaro A. Cheung, Laurene S. Beck, Sarah Andrade, Bruno de Bezerril Jain, Sanjay Bishai, William R. |
| author_role |
author |
| author2 |
Maiga, Mariama C. Ihms, Elizabeth A. Maiga, Mamoudou Ordonez, Alvaro A. Cheung, Laurene S. Beck, Sarah Andrade, Bruno de Bezerril Jain, Sanjay Bishai, William R. |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Ahidjo, Bintou A. Maiga, Mariama C. Ihms, Elizabeth A. Maiga, Mamoudou Ordonez, Alvaro A. Cheung, Laurene S. Beck, Sarah Andrade, Bruno de Bezerril Jain, Sanjay Bishai, William R. |
| dc.subject.other.pt_BR.fl_str_mv |
Tuberculose Granuloma Fibrose pulmonar idiopática Infecção Pirazinamida Tratamento |
| topic |
Tuberculose Granuloma Fibrose pulmonar idiopática Infecção Pirazinamida Tratamento Idiopathic Pulmonary Fibrosis Anti-Infective Agents Tuberculosis Pyrazinamide Treatment Failure Granuloma |
| dc.subject.en.pt_BR.fl_str_mv |
Idiopathic Pulmonary Fibrosis Anti-Infective Agents Tuberculosis Pyrazinamide Treatment Failure Granuloma |
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NIH |
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2016 |
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2016-10-17T12:32:58Z |
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2016-10-17T12:32:58Z |
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2016 |
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AHIDJO, B. A. et al. The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis. JCI Insight, v. 1, n. 14, p. e86017, 2016. |
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https://www.arca.fiocruz.br/handle/icict/16252 |
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2379-3708 |
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10.1172/jci.insight.86017 |
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AHIDJO, B. A. et al. The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis. JCI Insight, v. 1, n. 14, p. e86017, 2016. 2379-3708 10.1172/jci.insight.86017 |
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