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\begin{document}

\title{Elexacaftor/ivacaftor/tezacaftor effect on microbial density and the
microbiome composition.}



\author[1]{Yaron Fireizen}%
\author[1]{Bugsu Ovunc}%
\author[1]{Inderpal Randhawa}%
\author[2]{Janina Krumbeck}%
\author[3]{Nathan Marsteller}%
\author[1]{Celeste Bangol}%
\author[1]{Jagmohan Batra}%
\affil[1]{Miller Children's and Women's Hospital Long Beach}%
\affil[2]{Zymo Research Corporation}%
\affil[3]{Translational Pulmonary and Immunology Research Center (TPIRC) 701 E 28th St #419 Long Beach CA}%


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  \date{May 14, 2024}


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\begin{abstract}
Introduction Previous generations of CFTR modulation have been shown to
temporarily decrease the frequency of culture positivity of \emph{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 \emph{P. aeruginosa} (1.5 vs 1.19, p= 0.01),
\emph{S. aureus} (2.47 vs 1.9, p= 0.002), \emph{A. denitrificans} (1.39
vs,1.14, p=0.02), \emph{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 \emph{: S. salivarius}, \emph{S.
parasanguinis}, \emph{R. mucilaginosa}, \emph{V. atypica}, and \emph{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 ( \emph{S.
salivarius}, \emph{S. parasanguinis}, \emph{R. mucilaginosa}, \emph{V.
atypica}, and \emph{P. histocola}) that have been linked to improved
clinical lung stability, lower airway inflammation and increased
polymicrobial diversity.%
\end{abstract}%



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\verb`CF ped pulm.docx`  available at \url{https://authorea.com/users/412719/articles/580914-elexacaftor-ivacaftor-tezacaftor-effect-on-microbial-density-and-the-microbiome-composition}

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