Abstract
The study objective was to identify changes in cystic fibrosis (CF) sputum microbiology over 13 years. This study recruited a contemporary cohort of CF patients meeting similar eligibility criteria as the 520 subjects in the Phase 3 trials of inhaled tobramycin (historical cohort). Subjects submitted a single sputum specimen to a centralized laboratory for culture and susceptibility testing. Data were summarized and cross-sectional prevalence estimates were compared between cohorts. Exploratory analyses examined associations between recent antibiotic exposures and resistance prevalence. Sputum samples from 267 subjects from 33 US CF centers were submitted for testing. A total of 656 Pseudomonas aeruginosa isolates were identified from 253 culture-positive subjects. Comparison between cohorts revealed an increase in the prevalence of subjects with tobramycin resistant (11.8% vs. 30.4%, P < 0.001) and amikacin resistant (24.2% vs. 42.7%, P < 0.001) P. aeruginosa. Prevalence of ciprofloxacin resistance was similar (34.4% vs. 33.6%, P = 0.81). Within the contemporary cohort, potential associations between recent antibiotic exposures and prevalence of P. aeruginosa resistance were examined; findings included that exposure to intravenous carbapenems was significantly associated with aztreonam resistance, meropenem resistance, and multidrug resistance (P = 0.0002, P = 0.0003, and P = 0.0002, respectively). Prevalences of Staphylococcus aureus, methicillin-resistant S. aureus, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans were also increased in the contemporary cohort. We identified important changes in the patterns of CF airway microbiology, including increased aminoglycoside resistance and prevalence of other antibiotic resistant organisms. These changes are concerning to clinicians caring for individuals with CF because they impact treatment options. These data point to a critical need to develop new antimicrobials for CF.
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