{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T09:46:10Z","timestamp":1792835170137,"version":"4.5.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["569246"],"award-info":[{"award-number":["569246"]}]},{"name":"John Hunter Hospital Charitable Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The macrolide antibiotic azithromycin reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination of antibiotic-resistant organisms can occur, calling into question the long-term safety of azithromycin maintenance therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic resistance genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>16S rRNA sequencing and quantitative PCR were performed to assess the effect of azithromycin on sputum microbiology from participants of the AMAZES (Asthma and Macrolides: The Azithromycin Efficacy and Safety) trial: a 48-week, double-blind, placebo-controlled trial of thrice-weekly 500 mg oral azithromycin in adults with persistent uncontrolled asthma. Pooled-template shotgun metagenomic sequencing, quantitative PCR, and isolate whole-genome sequencing were performed to assess antibiotic resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Paired sputum samples were available from 61 patients (n\u2009=\u200934 placebo, n\u2009=\u200927 azithromycin). Azithromycin did not affect bacterial load (P\u2009=\u20090.37) but did significantly decrease Faith\u2019s phylogenetic diversity (P\u2009=\u20090.026) and Haemophilus influenzae load (P\u2009&amp;lt;\u20090.0001). Azithromycin did not significantly affect levels of Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, or Moraxella catarrhalis. Of the 89 antibiotic resistance genes detected, five macrolide resistance genes and two tetracycline resistance genes were increased significantly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with persistent uncontrolled asthma, azithromycin reduced airway H. influenzae load compared with placebo but did not change total bacterial load. Macrolide resistance increased, reflecting previous studies. These results highlight the need for studies assessing the efficacy of nonantibiotic macrolides as a long-term therapy for patients with persistent uncontrolled asthma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201809-1739oc","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T15:24:12Z","timestamp":1552663452000},"page":"309-317","source":"Crossref","is-referenced-by-count":176,"title":["Long-Term Azithromycin Reduces\n                    <i>Haemophilus influenzae<\/i>\n                    and Increases Antibiotic Resistance in Severe Asthma"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4357-8243","authenticated-orcid":false,"given":"Steven L.","family":"Taylor","sequence":"first","affiliation":[{"name":"South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia"},{"name":"South Australian Health and Medical Research Institute Microbiome Research Laboratory, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-2272","authenticated-orcid":false,"given":"Lex E. 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