Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum
Background: Cysteamine has recently been shown to have in vitro properties potentially therapeutically beneficial in cystic fibrosis (CF). In this study we investigated the antimicrobial and mucolytic activity of cysteamine against the complex biologic matrix of CF sputum. Methods: Sputum samples we...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-10-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396415301109 |
| _version_ | 1818603512764825600 |
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| author | Graham Devereux Douglas Fraser-Pitt Jennifer Robertson Edward Devlin Derry Mercer Deborah O'Neil |
| author_facet | Graham Devereux Douglas Fraser-Pitt Jennifer Robertson Edward Devlin Derry Mercer Deborah O'Neil |
| author_sort | Graham Devereux |
| collection | DOAJ |
| description | Background: Cysteamine has recently been shown to have in vitro properties potentially therapeutically beneficial in cystic fibrosis (CF). In this study we investigated the antimicrobial and mucolytic activity of cysteamine against the complex biologic matrix of CF sputum.
Methods: Sputum samples were obtained from 23 CF adults. Sputum polymicrobial content after in vitro exposure to cysteamine and standard CF antibiotics was assessed after a single exposure and after 14 days low-dose exposure. The effect of cysteamine on sputum spinnbarkeit was assessed.
Findings: Cysteamine reduced sputum polymicrobial burden by 3 · 18 (95% CI 2 · 30–4 · 07, p < 0.001) log10 units after 24 h incubation. Combined cysteamine and tobramycin reduced polymicrobial burden by a further 3 · 75 (95% CI 2 · 63–5 · 07, p < 0 · 001) log10 units above that seen with tobramycin. Repeated low dosing with cysteamine reduced sputum polymicrobial load from day 10 onwards (p = 0.032). Cysteamine reduced CF sputum viscoelasticity, sputum spinnbarkeit cysteamine 11.1 mm/s (95% CI 3.95–18.2) vs DNAse 1.69 mm/s (95% CI 0.73–2.65), p = 0.016. Cysteamine was active against Mycobacterium abscessus as a monotherapy and also potentiated the effects of amikacin and azithromycin.
Conclusion: Further investigation is required into the therapeutic potential of cysteamine in CF to treat emerging as well as established microbial pathogens and as a mucolytic agent. |
| first_indexed | 2024-12-16T13:24:21Z |
| format | Article |
| id | doaj.art-6f88c9b4b92240dd9cd82dd58a70c85d |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-16T13:24:21Z |
| publishDate | 2015-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-6f88c9b4b92240dd9cd82dd58a70c85d2022-12-21T22:30:16ZengElsevierEBioMedicine2352-39642015-10-012101507151210.1016/j.ebiom.2015.08.018Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in SputumGraham Devereux0Douglas Fraser-Pitt1Jennifer Robertson2Edward Devlin3Derry Mercer4Deborah O'Neil5Respiratory Group, University of Aberdeen, Aberdeen AB25 2ZG, UKNovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UKNovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UKRespiratory Group, University of Aberdeen, Aberdeen AB25 2ZG, UKNovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UKNovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UKBackground: Cysteamine has recently been shown to have in vitro properties potentially therapeutically beneficial in cystic fibrosis (CF). In this study we investigated the antimicrobial and mucolytic activity of cysteamine against the complex biologic matrix of CF sputum. Methods: Sputum samples were obtained from 23 CF adults. Sputum polymicrobial content after in vitro exposure to cysteamine and standard CF antibiotics was assessed after a single exposure and after 14 days low-dose exposure. The effect of cysteamine on sputum spinnbarkeit was assessed. Findings: Cysteamine reduced sputum polymicrobial burden by 3 · 18 (95% CI 2 · 30–4 · 07, p < 0.001) log10 units after 24 h incubation. Combined cysteamine and tobramycin reduced polymicrobial burden by a further 3 · 75 (95% CI 2 · 63–5 · 07, p < 0 · 001) log10 units above that seen with tobramycin. Repeated low dosing with cysteamine reduced sputum polymicrobial load from day 10 onwards (p = 0.032). Cysteamine reduced CF sputum viscoelasticity, sputum spinnbarkeit cysteamine 11.1 mm/s (95% CI 3.95–18.2) vs DNAse 1.69 mm/s (95% CI 0.73–2.65), p = 0.016. Cysteamine was active against Mycobacterium abscessus as a monotherapy and also potentiated the effects of amikacin and azithromycin. Conclusion: Further investigation is required into the therapeutic potential of cysteamine in CF to treat emerging as well as established microbial pathogens and as a mucolytic agent.http://www.sciencedirect.com/science/article/pii/S2352396415301109CysteamineCystic fibrosisMycobacterium abscessusPseudomonas aeruginosaSputum |
| spellingShingle | Graham Devereux Douglas Fraser-Pitt Jennifer Robertson Edward Devlin Derry Mercer Deborah O'Neil Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum EBioMedicine Cysteamine Cystic fibrosis Mycobacterium abscessus Pseudomonas aeruginosa Sputum |
| title | Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum |
| title_full | Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum |
| title_fullStr | Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum |
| title_full_unstemmed | Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum |
| title_short | Cysteamine as a Future Intervention in Cystic Fibrosis Against Current and Emerging Pathogens: A Patient-based ex vivo Study Confirming its Antimicrobial and Mucoactive Potential in Sputum |
| title_sort | cysteamine as a future intervention in cystic fibrosis against current and emerging pathogens a patient based ex vivo study confirming its antimicrobial and mucoactive potential in sputum |
| topic | Cysteamine Cystic fibrosis Mycobacterium abscessus Pseudomonas aeruginosa Sputum |
| url | http://www.sciencedirect.com/science/article/pii/S2352396415301109 |
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