Use of elexacaftor/tezacaftor/ivacaftor leads to changes in detection frequencies of Staphylococcus aureus and Pseudomonas aeruginosa dependent on age and lung function in people with CF.

The impressive improvements of CFTR function by elexacaftor/tezacaftor/ivacaftor (ETI) result in changes in the detection frequencies of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). We assessed determinants of the response to ETI with regards to SA and PA detection frequencies as documented in the German CF Registry for people with CF (pwCF) ≥12 years. We evaluated changes in the detection frequencies of SA and PA for 21 months before and after initiation of ETI and used different statistical tests to identify determinants of detection changes. We included data from 1,092 pwCF with results from culture-dependent diagnostics for SA and PA detection from 7,944 microbiological samples prior and 6.845 microbiological samples after initiation of ETI. Detections of SA decreased from 54.3% to 44.3% and 40.2% and those of PA from 39.9% to 31.9% and 22.6% 3 and 21 months after initiation of therapy, respectively (all p<0.001). Reduction of SA and PA were observed in throat swabs and sputa, associated significantly with age, prior lung function and were dependent on pre-ETI colonization status. The different patterns of reductions of SA and PA suggest that pathogen-specific biological processes govern the responsiveness of microbiological colonization towards ETI in pwCF.

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Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AMD reports receiving money paid to her institution for performance of clinical studies with CFTR modulators and personal remuneration by Vertex Pharmaceuticals Inc. for medical education writing (12/2023) and participation in an advisory board (12/2021). She received grants from the German Ministry for Health and Education (grant number 82DZL002A1) and the German Science Foundation (grant number DI 1224/6-1). She is unpaid member of the executive board of the German patients’ advocacy group on CF, member of the scientific advisory board and the registry advisory board of Muko e.V. SS reports no conflict of interest. LN reports receiving money paid to his institution for performance of clinical studies and personal remuneration from Articulate Science for medical writing. He is unpaid member of the Trial Steering Committee for CF STORM, medical lead of the German CF Registry and pharmacovigilance study manager of the European Cystic Fibrosis Society Patient Registry (ECFSPR). MB and SH report publication support by Chiesi Inc. paid to the Mukoviszidose Institute gGmbH (MI). BT reports receiving grant support by the German Science Foundation and personal remuneration from Vertex Pharmaceutical Inc. for educational events and lectures and the Helmholtz Institut für Infektionsforschung.