Chronic Azithromycin Use in Cystic Fibrosis and Risk of Treatment-Emergent Respiratory Pathogens

Ann Am Thorac Soc. 2018 Jun;15(6):702-709. doi: 10.1513/AnnalsATS.201801-012OC.

Abstract

Rationale: Azithromycin has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis. Concerns remain, however, regarding the potential emergence of treatment-related respiratory pathogens.

Objectives: To determine whether chronic azithromycin use (defined as three-times weekly administration) is associated with increased rates of detection of eight specific respiratory pathogens.

Methods: We performed a new-user, propensity score-matched retrospective cohort study utilizing data from the Cystic Fibrosis Foundation Patient Registry. Incident azithromycin users were propensity score matched 1:1 with contemporaneous nonusers. Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate the association between chronic azithromycin use and incident respiratory pathogen detection. Analyses were performed separately for each pathogen, limited to patients among whom that pathogen had not been isolated in the 2 years before cohort entry.

Results: After propensity score matching, the mean age of the cohorts was approximately 12 years. Chronic azithromycin users had a significantly lower risk of detection of new methicillin-resistant Staphylococcus aureus, nontuberculous mycobacteria, and Burkholderia cepacia complex compared with nonusers. The risk of acquiring the remaining five pathogens was not significantly different between users and nonusers.

Conclusions: Using an innovative new-user, propensity score-matched study design to minimize indication and selection biases, we found in a predominantly pediatric cohort that chronic azithromycin users had a lower risk of acquiring several cystic fibrosis-related respiratory pathogens. These results may ease concerns that chronic azithromycin exposure increases the risk of acquiring new respiratory pathogens among pediatric patients with cystic fibrosis.

Keywords: cystic fibrosis; macrolides; methicillin-resistant Staphylococcus aureus; microbiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin / therapeutic use*
  • Child
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / drug therapy
  • Drug Resistance, Bacterial*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Mycobacterium Infections, Nontuberculous / complications
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Nontuberculous Mycobacteria / isolation & purification
  • Propensity Score*
  • Pseudomonas Infections / complications
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / isolation & purification
  • Retrospective Studies
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Azithromycin