[HTML][HTML] Cysteamine as a future intervention in cystic fibrosis against current and emerging pathogens: a patient-based ex vivo study confirming its antimicrobial and …

G Devereux, D Fraser-Pitt, J Robertson, E Devlin… - …, 2015 - thelancet.com
G Devereux, D Fraser-Pitt, J Robertson, E Devlin, D Mercer, D O'Neil
EBioMedicine, 2015thelancet.com
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 14days low-dose exposure. The effect of cysteamine on 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 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 14days 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 24h 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 11.1mm/s (95% CI 3.95–18.2) vs DNAse 1.69mm/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.
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