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Potential role of macrolide antibiotics in the management of cystic fibrosis lung disease

Current management of cystic fibrosis (CF) lung disease includes the use of antibiotics, nutritional support, and airway clearance therapies. However, despite recent advances in pharmacologic therapies including DNase and aerosolized tobramycin, deterioration in lung function persists. Recent investigations have shed new light on the pathogenic mechanisms by which Pseudomonas aeruginosa establishes itself within the airways of patients with CF and contributes to the progressive decline in lung function. In particular, the presence of biofilms and other virulence mechanisms allow evasion of local host defenses and establishment of a chronic localized inflammatory response resulting in lung damage. Macrolide antibiotics appear to have a promising role in the management of CF lung disease even though they do not exhibit intrinsic antipseudomonal activity. Recent evidence demonstrates that they can disrupt quorum sensing, a cell-to-cell signaling process linked to the formation of biofilms. In addition, they inhibit NF-&kgr;b and AP-1, nuclear factors that control the expression of proinflammatory cytokines. Their ability to decrease sputum viscosity and increase sputum clearance may complement existing airway clearance therapies. Preliminary clinical trials have shown modest improvement in pulmonary function.