Changes in Airway Sampling and Pseudomonas aeruginosa Isolation after the Introduction of Elexacaftor/Tezacaftor/Ivacaftor.

RATIONALE: The impact of elexacaftor/tezacaftor/ivacaftor (ETI) on provision of airway samples, chronic infection definitions, and Pseudomonas aeruginosa (Pa) isolation frequency and abundance in those with established chronic Pa infection before ETI is unknown.

OBJECTIVES

To retrospectively analyse the impact of ETI on airway sampling and infection in those with chronic Pa at the time of ETI initiation.

METHODS

This was a retrospective cohort study of 211 people with cystic fibrosis at Royal Brompton with Leeds-defined chronic Pa infection either -1 or -2 years before ETI. Electronic patient records were analyzed 5 years before (-5 to -1) and 2 years after (+1 and +2) ETI for: number/type of airway samples provided per person per year (pppy), Pa (mucoid/nonmucoid) culture results (to calculate isolation frequency), and Pa abundance (log-transformed median cfu/ml).

RESULTS

A total of 148 patients had complete data; 136 provided one or more airway samples per year. Year -1 coincided with the coronavirus disease (COVID-19) pandemic. Comparisons are made from Year -2 to Years +1 and +2, finding sustained reduction in: samples provided pppy (yr, mean [standard deviation (SD)]: -2, 8.0 [4.5]; +1, 3.0 [2.5]; P < 0.0001; +2, 2.9 [2.2]; P < 0.0001), proportion of people meeting Standards of Care of four or more samples pppy (Year -2, 90%; Year +1, 31%; Year +2; P < 0.0001), proportion of Pa-positive samples (Year -2, 84.1%; Year +1, 66.1%; P < 0.0001; Year +2, 58.3%; P < 0.0001), proportion exhibiting mucoid phenotype (Year -2, 62.1%; Year +1, 48.4%; P < 0.001; Year +2, 43.6%; P < 0.0001), and median mucoid and nonmucoid Pa abundance (1-2 log cfu/ml).

CONCLUSIONS

Introduction of ETI coincides with reduced sample provision pppy; a minority of patients now meet Standards of Care (four or more samples pppy), challenging the use of current chronic infection definitions. Use of ETI, even in those with established chronic Pa and mucoid phenotype, coincides with reduced Pa isolation frequency/abundance.