Chronic airways infection with Pseudomonas aeruginosa (PA) is associated with increased frequency of exacerbations, deterioration in quality of life and increased mortality in adult patients with bronchiectasis. Current guidelines suggest the prescription of an eradication antibiotic treatment for a first episode of PA infection (early PA infection). Several antibiotic regimens may be proposed, ranging from a monotherapy with oral fluoroquinolone (FQ) to an intravenous cotherapy with the addition of inhaled antibiotics that seems to improve the rate of PA eradication. As no study strictly favoured one regimen, current practices are heterogeneous and could certainly benefit from stronger evidence, with both medical and economic impact.
≥18 years of age
Diagnosis of bronchiectasis on thoracic CT-scan
Recent isolation of P. aeruginosa (PA) in a respiratory sample (spontaneous or induced sputum or other lower respiratory tract sample obtained by bronchoscopy) within the last 3 months, with a PA positive respiratory sample obtained ≤ 3 weeks before randomization
Patient either Pseudomonas naive (i.e., never previously isolated PA) or Pseudomonas free (i.e., infection-free for ≥1 year, proven by at least two PA negative respiratory sample during the last year)
Confirmed diagnosis of cystic fibrosis
Pregnancy or breastfeeding
Women of childbearing potential (after the first menstrual period and until menopause or permanent sterility (hysterectomy, bilateral salpingectomy and bilateral oophorectomy)) who refuse to use effective contraception (hormonal or mechanical) for 3 months and/or to undergo pregnancy tests at baseline, 1 month and 3 months after baseline.
Isolation of PA in a respiratory specimen (spontaneous or induced sputum or other lower respiratory tract specimen obtained by bronchoscopy) more than 3 months to 12 months prior to randomization.
Parallel
Antibiotic monotherapy treatment and follow-up
Drug1. a 3-months treatment period, including: * an initial phase of 14 days, combining an oral fluoroquinolone (ciprofloxacin 750mg tw/d) with nebulized sodium colistimethate (1 Million Units tw/d) * a maintenance phase of 2.5 months: nebulized sodium colistimethate (1 MU tw/d) ; 2. a subsequent follow-up period of 9 months (i.e. until 12 months after the start of antibiotic therapy against Pseudomonas aeruginosa).
Antibiotic bitherapy treatment and follow-up
Drug1. a 3-months treatment period, including: * an initial phase of 14 days, combining an IV beta-lactam antibitic (ceftazidime 4 or 6g/d) and an oral fluoroquinolone (ciprofloxacin 750mg tw/d) with nebulized sodium colistimethate (1 Million Units tw/d) * a maintenance phase of 2.5 months: nebulized sodium colistimethate (1 MU tw/d) ; 2. a subsequent follow-up period of 9 months (i.e. until 12 months after the start of antibiotic therapy against Pseudomonas aeruginosa).
PA-eradication rate
PA-eradication rate 6 months after the start of antibiotic therapy targeting PA, where PA eradication is defined as follows: * Sputum culture (or lower airway specimen culture, if respiratory exacerbation\* with inability to perform good quality sputum analysis) negative for PA at the 6-month follow-up visit, or * Inability to spit in the absence of a pulmonary exacerbation\*, AND * No sputum culture or lower airway specimen positive for PA between D90 of antibiotic treatment and the 6-month follow-up visit, in the absence of new antibiotic therapy targeting PA.
Time to first exacerbation
exacerbation assessment at each follow-up visit, with time (in days) between the start of antibiotic therapy against PA and first exacerbation
1 year-exacerbation rate
exacerbation assessment at each follow-up visit
Quality-of-life using questionnaires
Quality of Life-Bronchiectasis (QOL-B)
Quality-of-life using questionnaires
Bronchiectasis Impact Measure (BIM)
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Centre Hospitalier Intercommunal Creteil
Lead sponsor
Assistance Publique - Hôpitaux de Paris
Collaborator
