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

• Cysteamine may have a role in treating cystic fibrosis.
• Cysteamine was added to sputum samples from 23 patients with cystic fibrosis.
• Cysteamine reduced microbial load and increased the effectiveness of tobramycin.
• Cysteamine greatly reduced the viscoelasticity of sputum.
• Cysteamine had activity against the emerging pathogen Mycobacterium abscessus.Cystic fibrosis (CF) is a genetic disease that damages the lungs because the thick sticky mucus produced in CF airways becomes infected. There is a need to develop new treatments for CF lung infections. In this study we have taken sputum samples from 23 people with CF and shown that an investigational drug cysteamine reduces the number of bacteria in the sputum and also makes an antibiotic work better. Cysteamine also reduced sputum stickiness. These results suggest that cysteamine may have a role treating CF lung infections and further research is required to fully assess this.

BackgroundCysteamine 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.MethodsSputum 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.FindingsCysteamine 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.ConclusionFurther 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.