110 Aztreonam for inhalation solution (AZLI) for eradication of new onset Pseudomonas aeruginosa (PA) infection in children with cystic fibrosis (CF): Evaluation of treatment failures

Objectives In the ALPINE study (ClinicalTrials.gov NCT01375049), AZLI treatment for 28 days in children with CF age 3 months to PA infection resulted in culture-negativity in 89% of patients (pts) at end of treatment and in 75% of pts at 28 days post-treatment. Post-hoc analyses were performed to determine possible factors associated with failure to eradicate or regrowth of PA post-treatment. Methods Children age 3 mos to PA infection (first lifetime PA -positive culture [throat swab, sputum, BAL] or PA -positive after ≥2-yr history of PA -negative cultures) were treated with AZLI 75 mg 3x/day for 28 days via PARI Investigational eFlow® Nebulizer. Evaluable pts received a full 28 day AZLI course and no additional anti- PA antibiotics. Baseline (BL) factors were compared for pts with post-treatment cultures PA -positive vs. those who were PA -negative. Results 99 treated pts had culture data available at 28d post-treatment: PA was present in 23; absent in 76. No differences were seen in age, CF genotype, history of prior PA infection, FEV1 % predicted, PA antibody status, or presence of co-infecting pathogens at BL in PA present vs. absent groups. 22/23 pts who failed eradication were >90% treatment compliant. MIC50&90 were unchanged in PA strains isolated post-treatment vs. BL (4, 8 mg/mL respectively). Conclusion No BL factors examined predicted PA culture positivity after a 28-day course of AZLI. Inhaled antibiotic treatment is warranted for all pts with new onset PA infection. Further studies are needed to determine optimal treatment strategies for initial eradication failures. Supported by Gilead Sciences.