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 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-kappab 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.
Nguyen
Thao
T
School of Pharmacy, University of Southern California, Los Angeles 90089-9121, USA.
Louie
Stan G
SG
Beringer
Paul M
PM
Gill
Mark A
MA
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D018942:Macrolides; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000209:etiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018942:Macrolides