Cystic Fibrosis-Related Pathogen Risk With Chronic Azithromycin Use

In a predominantly pediatric population of patients with cystic fibrosis (CF), chronic azithromycin users had a lower risk of acquiring several CF-related respiratory pathogens, according to the results of a study published in the Annals of the American Thoracic Society.

Jonathan D. Cogen, MD, MPH, from the Seattle Children’s Hospital in Washington, and colleagues conducted a new-user, propensity-score-matched retrospective cohort study using data from the Cystic Fibrosis Foundation Patient Registry (CFFPR). The investigators propensity-score-matched incident azithromycin users with contemporaneous nonusers. They used Kaplan-Meier curves and Cox proportional hazards regression to evaluate the association between chronic azithromycin use and time to acquisition of 8 specific CF respiratory pathogens.

A total of 7329 patients from the CFFPR in 2008 met the eligibility criteria. For both the azithromycin and the nonazithromycin cohorts, 400 matched pairs of respiratory pathogens were available for analysis. Compared with azithromycin nonusers, azithromycin users had a significantly lower risk for detection of new nontuberculous mycobacteria (NTM; hazard ratio [HR], 0.64; P =.017), methicillin-resistant Staphylococcus aureus (MRSA; HR, 0.65; P <.001), and Burkholderia cepacia complex (BCC; HR, 0.66; P =.024).

In addition, there was a trend noted toward higher risks for new multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) in azithromycin users compared with nonusers (HR, 1.31; P =.092). The investigators found no differences between azithromycin users and nonusers for risk for acquisition of the other study pathogens: Pseudomonas aeruginosa (Pa), Stenotrophomonas maltophilia, Aspergillus species, and Achromobacter xylosoxidans.

Azithromycin users also had significantly higher rates of exacerbations compared with nonusers in the Aspergillus (incidence rate ratio, 1.07; P =.002), MDR-Pa (incidence rate ratio, 1.06; P <.001), and Achromobacter xylosoxidans (incidence rate ratio, 1.06; P <.001) matched cohorts.

The authors hypothesized that azithromycin users would have higher risks for new acquisition of 8 important CF pathogens, but contrary to what they supposed, as well as evidence from previous small, single-center studies, azithromycin users had lower risks for new acquisition of 3 key CF pathogens (NTM, MRSA, and BCC), a trend toward higher rates of acquisition for one pathogen (MDR-Pa), and no difference for 4 other pathogens.

The authors also noted that patients who regularly received azithromycin were sicker on average compared with nonusers. However, the large population size and extensive clinical data contained in the CFFPR allowed the researchers to use propensity-score matching to minimize confounding by indication.

Reference

Cogen JD, Onchiri F, Emerson J, et al. Chronic azithromycin use in cystic fibrosis and risk of treatment-emergent respiratory pathogens [published February 23, 2018]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201801-012OC