Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model

Abstract COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone a...

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Autores principales:	Claire M. Naftalin, Rupangi Verma, Meera Gurumurthy, Kim Hor Hee, Qingshu Lu, Benjamin Chaik Meng Yeo, Kin Hup Tan, Wenwei Lin, Buduo Yu, Kok Yong Seng, Lawrence Soon-U Lee, Nicholas I. Paton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42cbd61d772947248c58c2e871ff77ab
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spelling	oai:doaj.org-article:42cbd61d772947248c58c2e871ff77ab2021-12-02T15:08:36ZAdjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model10.1038/s41598-018-31590-42045-2322https://doaj.org/article/42cbd61d772947248c58c2e871ff77ab2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31590-4https://doaj.org/toc/2045-2322Abstract COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA −0.10 ± 0.13ΔlogCFU versus −0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference −0.01, 95% CI −0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.Claire M. NaftalinRupangi VermaMeera GurumurthyKim Hor HeeQingshu LuBenjamin Chaik Meng YeoKin Hup TanWenwei LinBuduo YuKok Yong SengLawrence Soon-U LeeNicholas I. PatonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claire M. Naftalin Rupangi Verma Meera Gurumurthy Kim Hor Hee Qingshu Lu Benjamin Chaik Meng Yeo Kin Hup Tan Wenwei Lin Buduo Yu Kok Yong Seng Lawrence Soon-U Lee Nicholas I. Paton Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
description	Abstract COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA −0.10 ± 0.13ΔlogCFU versus −0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference −0.01, 95% CI −0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.
format	article
author	Claire M. Naftalin Rupangi Verma Meera Gurumurthy Kim Hor Hee Qingshu Lu Benjamin Chaik Meng Yeo Kin Hup Tan Wenwei Lin Buduo Yu Kok Yong Seng Lawrence Soon-U Lee Nicholas I. Paton
author_facet	Claire M. Naftalin Rupangi Verma Meera Gurumurthy Kim Hor Hee Qingshu Lu Benjamin Chaik Meng Yeo Kin Hup Tan Wenwei Lin Buduo Yu Kok Yong Seng Lawrence Soon-U Lee Nicholas I. Paton
author_sort	Claire M. Naftalin
title	Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
title_short	Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
title_full	Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
title_fullStr	Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
title_full_unstemmed	Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
title_sort	adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/42cbd61d772947248c58c2e871ff77ab
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Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model

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