Evidence map›Paper›PMID 21804191›Full record

ArticleThe Journal of clinical investigation2011

Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection.

Maurizio Renna, Catherine Schaffner, Karen Brown, Shaobin Shang, Marcela Henao Tamayo, Krisztina Hegyi, Neil J Grimsey, David Cusens, Sarah Coulter, Jason Cooper and 11 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed, 4 pooled it
16.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

152 citing papers in PubMed, 4 syntheses or guidelines pooled it, 307 citations in OpenAlex.

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92 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 4 institutions in 2 countries.

Maurizio RennaDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Catherine Schaffner
Karen Brown
Shaobin Shang
Marcela Henao Tamayo
Krisztina Hegyi
Neil J Grimsey
David Cusens
Sarah Coulter
Jason Cooper
Anne R Bowden
Sandra M Newton
Beate Kampmann
Jennifer Helm
Andrew Jones
Charles S Haworth
Randall J Basaraba
Mary Ann DeGroote
Diane J Ordway
David C Rubinsztein
R Andres Floto
University of Cambridge · GBColorado State University · USImperial College London · GBPapworth Hospital · GB

Funding

Medical Research Council MC_UP_A900_1122Wellcome Trust
6 · The paper itself

Abstract

Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens.

Indexed as

Anti-Bacterial AgentsAzithromycinAdultAnimalsAutophagyChlorocebus aethiopsCOS CellsCystic FibrosisDrug Resistance, BacterialEnzyme InhibitorsHeLa CellsHumansLysosomesMacrolidesMacrophagesMiceAnti-Bacterial AgentsAzithromycinbafilomycin A1Enzyme InhibitorsMacrolidesMAP1LC3A protein, humanMicrotubule-Associated ProteinsRecombinant Fusion ProteinsSirolimus

Identifiers

PMID21804191
PMCPMC3163956
OpenAlexW2016283787

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.