Abstract Rationale Chronic Pseudomonas aeruginosa colonization remains a leading cause of morbidity and mortality in adults with cystic fibrosis (CF). While CFTR modulators, such as Elexacaftor/Tezacaftor/Ivacaftor (ETI), have markedly improved lung function and reduced exacerbations, a subset of patients continues to experience colonization. Herein, we aim to identify risk factors associated with Pseudomonas colonization among adults with CF receiving ETI. Methods We conducted a single-center retrospective study of adults with confirmed CF on ETI. Data was collected on age, sex, BMI, race, CFTR genotype, spirometry, comorbidities, and exacerbation history. Subjects were classified as currently colonized (CC, two positive Pseudomonas respiratory cultures at least 3 months apart within a 12 month period), previously colonized (PC, at least 12 months period to date with 4 or more Pseudomonas-negative cultures after a period of colonization), or never colonized (NC). Primary analyses compared patients with any history of colonization (CC + PC) versus NC groups; secondary analyses compared CC and PC separately. Continuous and categorical variables were analyzed with t-tests and Fisher’s exact or Chi-square tests, respectively. Results Of the 84 adults on ETI, 34 (40.5%) had any Pseudomonas colonization status (13 CC, 21 PC), while 50 (59.5%) had never been colonized. Adults with any colonization status had higher annual exacerbation rates (0.85 vs 0.39; p=0.004) and were more likely to experience at least one exacerbation on ETI (82.4% vs 64.0%; p=0.068; OR 2.63; 95% CI 0.915 - 7.53). F508del genotype distribution differed significantly (p=0.03), with colonized subjects less likely to be F508del homozygous (38.2% vs 66.0%). Other factors were not significantly associated with colonization (age, sex, BMI, CFTR class, and diabetes). The CC subgroup showed lower ppFEV1 compared with NC (66.6% vs 86.2%; p=0.02). When comparing CC versus PC groups, only ppFEV1 had an association between the groups (66.6% vs 91.6%; p = 0.03), with exacerbation frequency trending higher in CC (1.13 per year vs 0.68 per year; p = 0.17). Conclusions Pseudomonas colonization was associated with having any exacerbation and higher exacerbation frequency. F508del mutations were associated with lower likelihood of any colonization. Patients with reduced ppFEV1 were less likely to clear Pseudomonas and had a trend of more exacerbations per year. Traditional pre-modulator risk factors (age, BMI, CFTR class, diabetes) were not predictive in this cohort, suggesting altered colonization determinants in the era of ETI. These findings underscore the need for novel, targeted strategies to prevent and eradicate Pseudomonas colonization in this evolving treatment landscape. This abstract is funded by: None
Ventura et al. (Fri,) studied this question.