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

Graham Devereux, Douglas Fraser-Pitt, Jennifer Robertson, Edward Devlin, Derry Mercer, Deborah O'Neill

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Abstract

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.
Original languageEnglish
Pages (from-to)1507-1512
Number of pages6
JournalEBioMedicine
Volume2
Issue number10
Early online date10 Aug 2015
DOIs
Publication statusPublished - Oct 2015

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Cysteamine
Sputum
Cystic Fibrosis
Tobramycin
Expectorants
Azithromycin
Amikacin
Mycobacterium
Anti-Bacterial Agents

Keywords

  • cysteamine
  • cystic fibrosis
  • mycobacterium abscessus
  • pseudomonas aeruginosa
  • sputum

Cite this

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. / Devereux, Graham; Fraser-Pitt, Douglas; Robertson, Jennifer ; Devlin, Edward; Mercer, Derry ; O'Neill, Deborah.

In: EBioMedicine, Vol. 2, No. 10, 10.2015, p. 1507-1512.

Research output: Contribution to journalArticle

Devereux, Graham ; Fraser-Pitt, Douglas ; Robertson, Jennifer ; Devlin, Edward ; Mercer, Derry ; O'Neill, Deborah. / 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. In: EBioMedicine. 2015 ; Vol. 2, No. 10. pp. 1507-1512.
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abstract = "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.",
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AU - Mercer, Derry

AU - O'Neill, Deborah

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N2 - 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.

AB - 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.

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