Inhaled antibiotics for the treatment of chronic bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis: systematic review of randomised controlled trials

Ramón y Cajal University Hospital, Unit of Bronchiestasis and Cystic Fibrosis, Respiratory Department , Madrid , Spain .
Expert Opinion on Pharmacotherapy (Impact Factor: 3.09). 04/2013; 14(9). DOI: 10.1517/14656566.2013.790366
Source: PubMed

ABSTRACT Introduction: Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosa chronic lung infection in cystic fibrosis (CF) patients. Areas covered: To summarise the available evidence, a systematic review of the three currently available inhaled antibiotics (aztreonam lysine (AZLI), colistin (COL) and tobramycin (TOB)) was performed. The three AZLI placebo-controlled studies showed that the improvements in FEV1 and mean sputum P. aeruginosa density were statistically significant better than with placebo. The two COL placebo-controlled studies involved few patients but showed that COL was better than placebo in terms of maintenance of some pulmonary function parameters. The tobramycin inhalation solution (TIS) and tobramycin inhalation powder studies showed that the efficacy of both formulations was similar but significantly better than placebo. In the comparative studies, TIS showed more efficacy than COL solution, colistin inhalation powder showed non-inferiority to TIS and AZLI was superior to TIS. Expert opinion: Placebo-controlled and comparative clinical trials have shown that clinical evidence of inhaled antibiotics is very different. The choice of treatment for each individual CF patient must be based on the features of the drug (clinical evidence on efficacy and safety), the inhalation system and the patient characteristics. Development of new inhaled antibiotics will allow new end points of efficacy and therapy regimens to be assessed.

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    ABSTRACT: Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene whose mortality is conditioned by a progressive decline in lung function. Bacterial infections play a key role in this decline. Chronic bacterial infection in CF patients varies over time and the presence of Pseudomonas aeruginosa in sputum is a marker of poor prognosis. P. aeruginosa is eradicated from the airways using inhaled antibiotics administered in various formulations and devices. Antipseudomonal antibiotics have extended the survival of CF patients to 40 years. Tobramycin is a bactericidal aminoglycoside antibiotic with demonstrated activity against gram-negative microorganisms. Initially, the drug was administered as an inhaled parenteral solution. Subsequently, a specific tobramycin inhalation solution was developed. PulmoSphere™ technology enables dry tobramycin powder to be formulated for inhalation (tobramycin inhalation powder) using a small and portable capsule-based breath-activated device (T-326). Chronic colonization by P. aeruginosa is the main indication for aerosol antibiotic therapy. The American Cystic Fibrosis Foundation, European guidelines, and Spanish consensus guidelines provide different recommendations for eradication.
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May 19, 2014