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Review
. 2024 Dec 4;33(174):240068.
doi: 10.1183/16000617.0068-2024. Print 2024 Oct.

Changing profile of bacterial infection and microbiome in cystic fibrosis: when to use antibiotics in the era of CFTR-modulator therapy

Justyna Milczewska  1   2   3 , Zulfiya Syunyaeva  4   3 , Aleksandra Żabińska-Jaroń  2 , Dorota Sands  1   2 , Stephanie Thee  5   6
Affiliations
Review

Changing profile of bacterial infection and microbiome in cystic fibrosis: when to use antibiotics in the era of CFTR-modulator therapy

Justyna Milczewska et al. Eur Respir Rev. .

Abstract

The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, especially the triple therapy combining the drugs elexacaftor, tezacaftor, ivacaftor (ETI), has significantly changed the course of the disease in people with cystic fibrosis (pwCF). ETI, which is approved for the majority (80-90%) of pwCF, partially restores CFTR channel function, resulting in improved mucociliary clearance and, consequently, improved lung function, respiratory symptoms and pulmonary exacerbations. The bacterial burden of classical CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus is reduced without reaching eradication in the majority of infected patients. Limited data is available on less common or emerging bacterial pathogens. ETI has a positive effect on the lung microbiome but does not fully restore it to a healthy state. Due to the significant reduction in sputum production under ETI, respiratory samples such as deep-throat swabs are commonly taken, despite their inadequate representation of lower respiratory tract pathogens. Currently, there are still unanswered questions related to this new therapy, such as the clinical impact of infection with cystic fibrosis (CF) pathogens, the value of molecular diagnostic tests, the durability of the effects on respiratory infection and the role of fungal and viral infections. This article reviews the changes in bacterial lung infections and the microbiome in CF to provide evidence for the use of antibiotics in the era of ETI.

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Conflict of interest statement

Conflict of interest: J. Milczewska reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceuticals (Poland) Sp. z o.o. Z. Syunyaeva reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceuticals, and support for attending meetings from Vertex Pharmaceuticals. A. Żabińska-Jaroń has nothing to disclose. D. Sands reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceuticals and Pfizer, support for attending meetings from Vertex Pharmaceuticals, participation on a data safety monitoring board or advisory board with Vertex Pharmaceuticals, and leadership roles with ECFS (Board member) and Polish CF Society (President). S. Thee reports payment or honoraria for lectures, presentations, manuscript writing or educational events from PARI Medical Holding, Vertex Pharmaceuticals and Viatris, support for attending meetings from Vertex Pharmaceuticals and Viatris, and leadership roles with ECFS (THCF working group and pulmonary exacerbation group) and ERS (CRC AMR-lung).

Figures

FIGURE 1
FIGURE 1
Frequency of respiratory tract infections in cystic fibrosis patients by age. Reproduced from [152]. MRSA: methicillin-resistant Staphylococcus aureus.
FIGURE 2
FIGURE 2
Effects of cystic fibrosis transmembrane conductance regulator modulator therapy (CFTRmt) on the lung and open questions regarding the effects of therapy. PEx: pulmonary exacerbation; pwCF: people with cystic fibrosis. Created with BioRender.com.
See this image and copyright information in PMC

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