REVIEW QUESTION

What is the efficacy of long-term inhaled antipseudomonal antibiotics in cystic fibrosis (CF)?

TYPE OF REVIEW

A systematic review of 18 randomized controlled trials (RCTs) and quasi-RCTs.

RELEVANCE FOR NURSING

Pseudomonas aeruginosa, a gram-negative bacterium commonly found in the environment, is a hostile pathogen for people with CF. A chronic disease of the lungs, CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located on chromosome 7. The CFTR gene affects chloride ion channels located in cell membranes of multiple organs, including the lungs. Diminished capacity for chloride movement through the cell membrane in the lung results in decreased flow of airway surface liquid, causing thick mucus that blocks airways and traps bacteria, leading to respiratory infection.

Inhaled antibiotics are used to manage P. aeruginosa infection in CF because they can deliver high-dose medication targeting lung infection. Although the use of inhaled antibiotics or a combination of antibiotics to manage P. aeruginosa in CF has been established, investigation of the clinical outcomes of long-term treatment for chronic infection in CF patients is needed.

CHARACTERISTICS OF THE EVIDENCE

This study is a systematic review of RCTs and quasi-RCTs that compared any inhaled antipseudomonal antibiotics given for a duration of three months with either inhaled placebo, no placebo, usual treatment, or another inhaled antipseudomonal antibiotic. Its objective was to determine the clinical outcomes of long-term inhaled antipseudomonal antibiotic therapy in CF. The primary outcomes were lung function, as measured by forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC), and exacerbation of respiratory infection, as determined by hospital admission data and treatment required. The secondary objectives were nutrition, quality of life, survival, antibiotic resistance, and adverse events.

Studies of people diagnosed with CF by sweat test or CFTR genealogy, of all ages and all severity of disease were included. The 18 trials that met the inclusion criteria had a combined 3,042 participants ages five to 56 years and a duration of three to 33 months. Five of the trials were included in a meta-analysis. The most commonly studied antibiotic was tobramycin. The review found improvement in the primary outcome of lung function as measured by FEV₁ and FVC and a reduction in respiratory exacerbation. The secondary outcomes of quality of life, nutrition, and survival were not adequately investigated in the included trials. The incidence of serious adverse effects was not common.

BEST PRACTICE RECOMMENDATIONS

This review of the long-term use of inhaled antipseudomonal antibiotics (as distinct from first-line treatment to eradicate P. aeruginosa or treatment to manage exacerbation) identified that the best evidence supports the use of tobramycin. Other inhaled antibiotics for which evidence is emerging include aztreonam, ciprofloxacin, levofloxacin, amikacin, and combined fosfomycin-tobramycin. This study did not identify clinical trials that supported long-term use of colistin to suppress P. aeruginosa.

RESEARCH RECOMMENDATIONS

Specific issues that should be the focus of future trials include determining the optimum tobramycin dose, frequency of treatment, and daily frequency of administration; comparing the benefits and harms of the various antibiotics, including a longer-term comparison of tobramycin and other inhaled antibiotics, and perhaps combinations; and determining the adverse effects of longer-term drug use, particularly on the relevance and impact of drug-resistant organisms.

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