ANTIMICROBIAL THERAPY FOR NEW ONSET PSEUDOMONAS AERUGINOSA AIRWAY INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive lung disease associated with chronic Pseudomonas aeruginosa (Pa) endobronchial infection and the associated intense neutrophilic inflammatory response. Bacterial infection and robust neutrophilic airway inflammation begin far earlier than previously understood, often prior to the onset of symptoms. The prevalence of Pa infection increases with age, with positive respiratory tract cultures reported for up to 20-30% of infants, 30-40% of children 2-10 years of age, approximately 60% of adolescents, and approximately 80% of adults with CF. Chronic Pa endobronchial infection is characterized by high concentrations of alginate-producing mucoidy Pa variants that may form biofilms rendering the organisms highly resistant to antibiotics in vivo. Once established, chronic Pa endobroncial infection is virtually impossible to eradicate. Pa infection is clearly associatd with poorer clinical outcomes, including more rapid decline in pulmonary function and higher mortality rates. Early age of Pa acquisition also adversely affects pulmonary disease and survival. This multicenter, randomized clinical trial is assessing the clinical and microbiologic efficacy and safety of treatment with antimicrobial therapy at the time of new onset of Pa positive oropharyngeal, sputum or lower respiratory tract culture in young children with CF. Subjects will be randomized to one of two early anti-pseudomonal treatment algorithms. All participants will receive an initial course of anti-pseudomonal antibiotic therapy consisting of 28 days of tobramycin solution for inhalation (TSI) and a 14-day course of oral ciprofloxicin/placebo regardless of randomization assignment. If respiratory cutlures samples after three weeks of the first anti-pseudomonal cycle remain Pa positive, participants will receive an additional 28-day course of TSI.