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Background: Consensus guidelines recommend early treatment to eradicate newly acquired Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients although there is no single preferred regimen. Aztreonam for inhalation solution (AZLI) significantly reduces sputum Pa density in CF patients with chronic Pa infection and has been well tolerated in the pediatric population. This single-arm, open-label Aztreonam Lysine for Pseudomonas Infection Eradication (ALPINE) study was conducted to evaluate the safety and efficacy of a 28-day treatment course of AZLI to eradicate newly acquired Pa infection in pediatric CF patients., Methods: CF patients (3 months to <18 years) with new onset Pa infection were treated with AZLI 75 mg 3 times daily for 28 days. New onset Pa infection was defined as first lifetime Pa-positive respiratory tract culture (throat swab, sputum) or Pa-positive culture after a ≥2-year history of Pa-negative cultures (≥ 2 cultures/year). Sputum or throat swab cultures were collected at study entry (baseline) and at weeks 4 (end of treatment), 8, 16, and 28. Primary endpoint was the percentage of patients with cultures negative for Pa at all post-treatment time points., Results: A total of 105 pediatric CF patients enrolled (3 months to <2 years, n=24; 2 to <6 years, n=25; 6 to <18 years, n=56). Of the 101 patients who completed treatment, 89.1% (n=90) were free of Pa at the end of treatment and 75.2% (n=76) were free of Pa 4 weeks after the end of treatment. Of the 79 patients evaluable for the primary endpoint, 58.2% were free of Pa at all post-treatment time points., Conclusions: AZLI was effective and well tolerated in eradicating Pa from newly infected pediatric patients with CF. These eradication rates are consistent with success rates reported in the literature for various antibiotic regimens, including other inhaled antibiotics studied for eradication. ClinicalTrials.gov: NCT01375049., (Copyright © 2014. Published by Elsevier B.V.)

Background: Open-label, parallel-group, international trial comparing aztreonam for inhalation solution (AZLI) and tobramycin nebulizer solution (TNS) for cystic fibrosis patients with airway Pseudomonas aeruginosa., Methods: 273 patients (≥ 6 years); randomized to three 28-day courses (AZLI 75 mg [three-times/day] or TNS 300 mg [twice/day]); 28 off-days separated each course., Results: 268 patients were treated (AZLI/TNS: 136/132). Mean baseline FEV1 was 52% predicted. Mean relative changes after 1 course (AZLI: 8.35%; TNS: 0.55%; p<0.001) and mean actual changes across 3 courses (AZLI: 2.05%; TNS: -0.66%; p=0.002) indicated AZLI statistical superiority vs. TNS. AZLI-treated patients had fewer respiratory hospitalizations (p=0.044) and respiratory events requiring additional antipseudomonal antibiotics (p=0.004); both treatments were well tolerated. 133 patients received 1 to 3 courses of AZLI treatment in the open-label extension-period (28-day courses separated by 28 days off-treatment); lung function improvements were comparable regardless of whether patients had received TNS or AZLI in the preceding comparative period., Conclusions: AZLI demonstrated statistical superiority in lung function and a reduction in acute pulmonary exacerbations compared to TNS over 3 treatment courses (ClinicalTrials.gov: NCT00757237)., (Copyright © 2012. Published by Elsevier B.V.)

Objectives Treating early PA infection in CF often requires giving inhaled antibiotics to very young patients (pts). In the ALPINE study ( ClinicalTrials.gov NCT01375049 ), pts <6 yrs old were allowed to use a facemask rather than the standard nebulizer mouthpiece. Post-hoc analysis was performed to compare results of AZLI treatment for pts using a facemask vs. mouthpiece. Methods Children age 3 mos to <18 yrs with CF and new onset 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 a PARI Investigational eFlow® Nebulizer. Recommended delivery was by SmartMask® Baby for pts 3 mos to <2 yrs, SmartMask Kids for 2 to <6 yrs, and by nebulizer mouthpiece for ≥6 yrs. Masks and mouthpiece were interchangeable to obtain optimal fit. Evaluable pts received a full 28 day AZLI course and no additional anti-PA antibiotics. Use of delivery devices by age group and respective PA eradication failure rates are presented. Results See the table. No specific safety issues were attributable to either mask or mouthpiece use. PA culture positive at day 28, end of treatment, n/N 3 mo to <2 yrs 2 to <6 yrs 6 to <18 yrs Total Masks 4/46 (8.7%)  SmartMask Baby 2/18 0/1 0/0  SmartMask Kid 1/5 1/19 0/3 Mouthpiece 0/0 0/4 6/50 6/54 (11.1%) Conclusion In young children with CF, AZLI treatment administered via eFlow nebulizer with SmartMask for initial PA infection had high eradication success rates and should be considered a valid treatment option. No safety issues were associated with specific mask/mouthpiece type. Supported by Gilead Sciences. [ABSTRACT FROM AUTHOR]

Objectives In the ALPINE study ( ClinicalTrials.gov NCT01375049), AZLI treatment for 28 days in children with CF age 3 months to <18 yrs with new onset 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 <18 yrs with CF and new onset 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. [ABSTRACT FROM AUTHOR]