loading page

Elexacaftor/ivacaftor/tezacaftor effect on microbial density and the microbiome composition.
  • +4
  • Yaron Fireizen,
  • Bugsu Ovunc,
  • Inderpal Randhawa,
  • Janina Krumbeck,
  • Nathan Marsteller,
  • Celeste Bangol,
  • Jagmohan Batra
Yaron Fireizen
Miller Children's and Women's Hospital Long Beach
Author Profile
Bugsu Ovunc
Miller Children's and Women's Hospital Long Beach
Author Profile
Inderpal Randhawa
Miller Children's and Women's Hospital Long Beach
Author Profile
Janina Krumbeck
Zymo Research Corporation
Author Profile
Nathan Marsteller
Translational Pulmonary and Immunology Research Center (TPIRC) 701 E 28th St #419 Long Beach CA
Author Profile
Celeste Bangol
Miller Children's and Women's Hospital Long Beach
Author Profile
Jagmohan Batra
Miller Children's and Women's Hospital Long Beach
Author Profile

Abstract

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 polymicrobial diversity.