(249) Impact of Elexacaftor/tezacaftor/ivacaftor on Pseudomonas aeruginosa Acquisition and Chronic Infection at a Single Pediatric Cystic Fibrosis Center

Background: As CF lung disease progresses, the airways become colonized with opportunistic pathogens, such as Pseudomonas aeruginosa (PA) secondary to airway surface liquid depletion. Acquisition of PA is associated with lung function decline, increased treatment burden, and mortality. In October 2019, the FDA approved elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective modulator therapy (HEMT) for individuals 12 and older with one copy of the F508del CFTR mutation. ETI increases the amount of and function of CFTR in the respiratory epithelium, improving mucociliary clearance (MCC) and reducing static airway mucous, a major trigger for chronic infection and inflammation.

Methods: A retrospective analysis of inhaled tobramycin (iTOB) prescriptions prescribed between 01 January 2016 to 31 December 2021 was performed. This captured data pre-and post-ETI approval at Children’s Mercy Kansas City (CMKC). The number of individuals with new PA acquisition was determined by identifying electronic prescriptions for iTOB eradication courses. An eradication course was defined as the first lifetime prescription for iTOB or a new prescription for iTOB sent with a duration of >1 year(s) prior to a previous prescription. The number of individuals considered chronically infected with PA was determined by identifying individuals receiving chronic iTOB prescriptions and confirmed by respiratory cultures indicating chronic infection based on the Leeds criteria (PA recovered in ≥50% of airway cultures in the previous 12 months).

Results: Eradication courses were prescribed to 34 individuals in 2016, which represented 15% of people receiving care at CMKC. The number of eradication prescriptions declined in 2020 and 2021 with only 15 (7%) and 12 (5%) individuals prescribed eradication therapy for those years, respectively. A similar pattern was observed for prescriptions for chronic infection. In 2016, 57 individuals, representing 25% of our patient population were receiving iTOB for chronic PA infection. A reduction was seen in 2020 and 2021 with 28 (13%) and 20 (9%) individuals prescribed chronic therapy for the respective years. The number of individuals prescribed iTOB for PA eradication and chronic infection per year is represented in Figure 1.

Conclusions: CMKC experienced a decrease in the number of courses of iTOB prescribed over the last 6 years. HEMT use is associated with increased MCC and anti-inflammatory effects impacting the airway microbiome. The decrease in respiratory cultures growing PA likely reflects these phenomena. A confounding factor is the SARS-CoV-2 pandemic and widespread use of HEMT. Clinic closures and implementation of telemedicine limited in-person patient visits during 2020 and 2021. Despite limited in-person visits, the average number of respiratory cultures per individual at CMKC in 2020 was 3.5, which is consistent with previous years. We were able to maintain frequent surveillance cultures through the implementation of a drive-through respiratory specimen collection process. Hence, the decreased number of iTOB courses cannot be attributed to decreased frequency of respiratory cultures. We cannot, however, assess the impact of school closures and decreased social gathering on new PA acquisition or chronic infection. Looking at all these variables, the widespread use of HEMT likely played a significant role in reducing both new PA acquisition and chronic PA infection.

Acknowledgements:

References: