Background: The goal of this study was to determine the association of multiple antibiotic-resistant Pseudomonas aeruginosa (MARPA) acquisition with lung function decline in patients with cystic fibrosis (CF). Methods: Using data from Epidemiologic Study of Cystic Fibrosis (ESCF), we identified patients with spirometry data and MARPA, defined as PA (1) resistant to gentamicin and either tobramycin or amikacin, and (2) resistant to ≥1 antipseudomonal beta lactam. MARPA had to be detected in a respiratory culture after ≥2years of PA-positive but MARPA-negative respiratory cultures. Multivariable piecewise linear regression was performed to model the annual rate of decline in forced expiratory volume in 1second (FEV 1) % predicted 2 calendar years before and after the index year of MARPA detection, adjusting for patient characteristics and CF therapies. Results: In total, 4349 patients with chronic PA and adequate PFT data were identified; 1111 subsequently developed MARPA, while 3238 patients were PA positive but MARPA negative. Compared with patients who did not acquire MARPA, MARPA-positive patients had lower FEV 1 and received more oral (p<0.013) and inhaled (p<0.001) antibiotic therapy. Mean FEV 1 decline did not change significantly after MARPA detection (-2.22% predicted/year before detection and -2.43 after, p=0.45). There was no relationship between persistent infection or FEV 1 quartile and FEV 1 decline. Conclusions: Newly detected MARPA was not associated with a significant change in the rate of FEV 1 decline. These results suggest that MARPA is more likely to be a marker of more severe disease and more intensive therapy, and less likely to be contributing independently to more rapid lung function decline.
Bibliographical noteFunding Information:
This study was sponsored by Genentech, Inc . C. Ren, W. Regelmann, and M. Konstan have received honoraria from Genentech, Inc., for serving as members of the Scientific Advisory Group for the Epidemiologic Study of Cystic Fibrosis (ESCF). C. Ren and M. Konstan have served as consultants to Genentech. No compensation was provided to these authors in exchange for production of this manuscript. L Rasouliyan is an employee of ICON Late Phase & Outcomes Research. ICON Late Phase & Outcomes Research was paid by Genentech for providing biostatistical services for this study. A. Yegin and B. Trzaskoma are currently employees of Genentech.
- Antibiotic resistance
- Lung infections