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.

According to current knowledge, the early combination of an oral FQ to an inhaled antibiotic could be an acceptable alternative to a systemic cotherapy. Indeed, such regimen allows avoiding IV drugs use, facilitating ambulatory management and influencing patient's quality of life and costs, and may achieve similar PA-eradication rate.

Inclusion Criteria:

• ≥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)
• Patient affiliated with the French health care system
• Able to understand and sign a written informed consent form

Exclusion Criteria:

• 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.
• PA resistant to ciprofloxacin or ceftazidime
• Severe exacerbation requiring admission to an intensive care unit (e.g. for non-invasive ventilatory support, invasive mechanical ventilation, catecholamine or any other organ supportive therapy)
• Prior severe reaction, hypersensitivity reaction or other contraindication to any of the treatments in study (ciprofloxacin, beta-lactam, colistimethate sodium)
• Prior severe bronchospasm attributed to a nebulization
• Patients already receiving PA suppressive therapy with an inhaled antibiotic (long-term azithromycin therapy accepted)
• Prior PA-eradication antibiotic treatment (systemic antibiotic(s) active against PA for ≥ 14 days or nebulized anti-PA antibiotic) within the last year
• Antibiotic treatment active against PA (anti-PA beta-lactam antibiotic and/or FQ and/or aminoglycoside) for more than 3 days before randomisation
• Active cancer or haematological malignancy under active therapy
• Systemic corticosteroid therapy ≥ 20 mg/d. prednisone equivalent for a predictable duration > 4 weeks
• Non-tuberculous mycobacterial infection or positive non-tuberculous mycobacterial respiratory specimen within 1 year prior to inclusion
• Severe chronic renal failure defined by a creatinine clearance (Cockcroft or MDRD) ≤ 30 mL/min/1.73m2 or chronic haemodialysis
• Severe hepatic impairment
• Long-term oxygen therapy and/or noninvasive mechanical ventilation for chronic respiratory insufficiency (except continuous positive airway pressure for OSA) and/or forced expiratory volume at one second (FEV1) <25% of predicted value.
• Patient participating to another interventional clinical trial