Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients.
Med
; 5(9): 1096-1111.e6, 2024 Sep 13.
Article
in En
| MEDLINE
| ID: mdl-38917792
ABSTRACT
BACKGROUND:
Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration.METHODS:
Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored.FINDINGS:
Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy.CONCLUSIONS:
Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation.FUNDING:
This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pseudomonas aeruginosa
/
Pseudomonas Infections
/
Staphylococcus aureus
/
Nebulizers and Vaporizers
/
Cystic Fibrosis
/
Antibodies, Neutralizing
/
Phage Therapy
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
Med
/
Med (New York. Online)
Year:
2024
Type:
Article
Affiliation country:
Spain