Elexacaftor/ivacaftor/tezacaftor effect on microbial density and the
Introduction Previous generations of CFTR modulation have been shown to
temporarily decrease the frequency of culture positivity of P.
aeruginosa and other respiratory pathogens. Recently, a three-drug
combination Trikafta (elexacaftor/ivacaftor/tezacaftor) was approved for
individuals with at least one F508del mutation. There is limited data on
the effect of CFTR modulators on bacterial density and CF microbiome.
Methods Our study included 2 separate forms of data collection: Firstly,
a retrospective chart evaluation of routine respiratory cultures 1.5
years before and after initiation of Trikafta. Respiratory culture
density was recorded based upon the growth fraction of standard
respiratory plate: none (0/4), scant (1/4), light (2/4), moderate (3/4),
and large (4/4). The second data measurement included obtaining
next-generation sequencing (NGS) for bacterial and fungal abundance of
post-Trikafta initiation patients only. Results There was a significant
density decrease in P. aeruginosa (1.5 vs 1.19, p= 0.01),
S. aureus (2.47 vs 1.9, p= 0.002), A. denitrificans (1.39
vs,1.14, p=0.02), E. coli (1.09 vs 1.00, p=0.045) before and
after initiation of Trikafta. On the NGS the 5 most abundant bacteria
after Trikafta initiation were : S. salivarius, S.
parasanguinis, R. mucilaginosa, V. atypica, and P.
histocola. Conclusion Our study results demonstrate that there is a
significant decrease in the density of known CF pathogenic bacteria. NGS
post-Trikafta has shown abundance of anaerobic bacteria ( S.
salivarius, S. parasanguinis, R. mucilaginosa, V.
atypica, and P. histocola) that have been linked to improved
clinical lung stability, lower airway inflammation and increased