Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis

Rationale The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown. Objectives To determine if failure of antibiotic therapy to eradicate Pa and frequency of Pa recurrence are associated with increased exacerbation risk. Methods The cohort included 282 children with CF who participated in the EPIC trial ages 1-12 with newly acquired Pa, defined as either a first lifetime Pa positive respiratory culture or positive after two years of negative cultures (past isolation of Pa but >2 years prior to the trial). All received antibiotics to promote initial eradication followed by 15 months of intermittent maintenance antibiotics. Quarterly cultures were used to define initial eradication success and subsequent number of Pa recurrences. A standardized symptom-based definition of exacerbation was utilized. Cox proportional hazards models were used to estimate exacerbation risk. Results Failure to initially eradicate Pa was associated with exacerbation risk (hazard ratio [HR]: 2.49, 95% confidence interval [CI] 1.26, 4.93). In 245/282 with successful initial eradication during the trial, past isolation of Pa >2 years before the trial was the most significant predictor of exacerbation (HR 1.62, 95% CI 1.12, 2.35). In 37/282 who failed initial eradication, persistent Pa during the maintenance phase (1 or more Pa recurrences after failure to initially eradicate) added even greater exacerbation risk (HR 4.13, 95% CI 1.28, 13.32). Conclusions Children with CF who fail to eradicate after initial antibiotic treatment are at higher risk of subsequent exacerbation, suggesting clinical benefit to successful early eradication of Pa infection.