Applying clinical outcome variables to appropriate aerosolized antibiotics for the treatment of patients with cystic fibrosis

Abstract

Commercial availability of more than one inhaled antibiotic for the management of chronic Pseudomonas aeruginosa lung infections in persons with cystic fibrosis creates a welcome question: Can different inhaled therapies be combined to improve patient outcomes? Although clinicians intuit that antibiotic alternation might extend the duration of benefit, prospective clinical trials will be unable to test this hypothesis. Rather, endpoints acceptable for demonstrating the efficacy of a chronic pulmonary therapy (lung function improvement/stabilization, reduction in exacerbation risk, improvement in quality of life) can test only whether the benefit amplitude is increased during fixed treatment periods. Reduction in pulmonary exacerbation risk appears to be best suited for this task, although lack of consensus on an objective definition of exacerbation independent of the decision to treat is a shortcoming. The broader clinical question of whether a patient has become refractory to a chronic therapy over time would be better addressed with a carefully conducted withdrawal study.