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.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Respiratory Group, University of Aberdeen, Aberdeen AB25 2ZG, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Devereux
authors.affiliation: NovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Fraser-Pitt
authors.affiliation: NovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Respiratory Group, University of Aberdeen, Aberdeen AB25 2ZG, UK ; NovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Devlin
authors.affiliation: NovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UK.
authors.forename: Derry
authors.initials: D
authors.lastname: Mercer
authors.affiliation: NovaBiotics Ltd, Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: O'Neil
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015169:Colony Count, Microbial; D003543:Cysteamine / Q000494:pharmacology* / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009170:Nontuberculous Mycobacteria / Q000187:drug effects / Q000302:isolation & purification; D009894:Opportunistic Infections / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology*; D013183:Sputum / Q000187:drug effects / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003543:Cysteamine
keywords: Cysteamine; Cystic fibrosis; Mycobacterium abscessus; Pseudomonas aeruginosa; Sputum