Impact of Sustained Eradication of New Pseudomonas aeruginosa Infection on Long-term Outcomes in Cystic Fibrosis

• Published in: Clinical infectious diseases 2015-09, Vol.61 (5), p.707-715
• Main Authors: Mayer-Hamblett, Nicole, Kloster, Margaret, Rosenfeld, Margaret, Gibson, Ronald L., Retsch-Bogart, George Z., Emerson, Julia, Thompson, Valeria, Ramsey, Bonnie W.
• Format: Article
• Language: English
• Subjects: and Commentaries; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; ARTICLES AND COMMENTARIES; Child; Child, Preschool; Children & youth; Cohort Studies; Confidence intervals; Cystic fibrosis; Cystic Fibrosis - epidemiology; Cystic Fibrosis - microbiology; Female; Follow-Up Studies; Gram-negative bacteria; Humans; Impact analysis; Infant; Male; Pseudomonas aeruginosa; Pseudomonas Infections - complications; Pseudomonas Infections - drug therapy; Pseudomonas Infections - epidemiology; Pseudomonas Infections - physiopathology; Treatment Outcome
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/civ377

Background. Pseudomonas aeruginosa (Pa) is the most important pathogen infecting the airways in individuals with cystic fibrosis. A key question is whether children with newly acquired Pa infection who are able to achieve sustained eradication after early antipseudomonal therapy demonstrate improved long-term health outcomes compared with those who are unable to achieve a sustained microbiologic response. Methods. This cohort study utilized observational follow-up data on children participating in the Early Pseudomonas Infection Control trial who received standardized therapy for newly acquired Pa. Sustained eradicators were defined as those who maintained Pa-negative cultures for 12 months after initial antipseudomonal therapy. Associations between eradication status and outcomes were assessed. Results. Of the 249 trial participants included in the study, 172 (69%) achieved sustained eradication of Pa during the trial (sustained eradicators). Over the median 5-year follow-up, sustained eradicators had a 74% reduced risk of developing chronic Pa (hazard ratio [HR], 0.26; 95% confidence interval [CI], 17–.40) and a 57% reduced risk of mucoidy (HR, 0.43; 95% CI, .25–.73) compared with nonsustained eradicators. Sustained eradicators had significantly less anti-Pa antibiotic usage during follow-up compared with nonsustained eradicators. There was no association between eradication status and clinical outcomes including rate of exacerbation and lung function decline. Conclusions. This is the first study to quantify the long-term durability of microbiological response associated with early antipseudomonal therapy, demonstrating the critical importance of optimizing antipseudomonal therapies during early Pa infection. The clinical impact of failure to achieve sustained Pa eradication remains unclear, however, and may be confounded by anti-Pa antibiotic usage. Clinical Trials Registration. NCT00097773.