Real-life effect of elexacaftor/tezacaftor/ivacaftor therapy on microbiological findings in patients with Cystic fibrosis

<bold>Introduction:</bold> The highly effective CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) improves CFTR function and clinical outcomes. A decrease in culture-based detection of P.aeruginosa (PA), but also persistent PCR detection of the pathogens present before ETI was described. <bold>Objectives:</bold> The objective of our study was to determine if ETI improved microbiological outcomes overtime. We hypothesized that positive cultures would decrease. <bold>Methods:</bold> Sputum cultures and throat swabs were prospectively collected in all patients treated with ETI in Verona CF center; also, samples of the 24 months before the start of ETI were extracted from our records. Only patients with at least 12 months of follow-up were included. Total yearly positivities for each pathogen were divided by the number of samples collected yearly on that patient. <bold>Results:</bold> We included 346 patients (F 53.7%, mean age 31.3 ±13.2, F/F genotype 34.4%), treated with ETI for mean 26.1 (±8.8) months. When considering the 1st year of ETI, S. maltophila (SM), A. xilosoxidans (AX), B. cepacia (BC), non-tuberculous-mycobacteria (NTM) and Scedosporium were less frequently isolated, in comparison to the year before ETI. When also the 2nd year of ETI was considered, a decrease in AX, SM and NTM was shown, though non significantly. Methicillin resistant S.aureus (MRSA) and PA findings did not change during ETI. A not significant increasing trend for PA, SM, BC could be seen from the 1st to the 2nd year of treatment. <bold>Conclusions:</bold> Improvements in respiratory cultures were seen on the 1st year of treatment; this was less clear during the 2nd year of ETI; PA and MRSA positive culture rates didn't change during ETI.