Details

Autor(en) / Beteiligte

• Taylor, Steven L
• Leong, Lex E X
• Mobegi, Fredrick M
• Choo, Jocelyn M
• Wesselingh, Steve
• Yang, Ian A
• Upham, John W
• Reynolds, Paul N
• Hodge, Sandra
• James, Alan L
• Jenkins, Christine
• Peters, Matthew J
• Baraket, Melissa
• Marks, Guy B
• Gibson, Peter G
• Rogers, Geraint B
• Simpson, Jodie L

Titel

Long-Term Azithromycin Reduces Haemophilus influenzae and Increases Antibiotic Resistance in Severe Asthma

Ist Teil von

• American journal of respiratory and critical care medicine, 2019-08, Vol.200 (3), p.309-317

Ort / Verlag

United States: American Thoracic Society

Erscheinungsjahr

2019

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic resistance genes. 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. Paired sputum samples were available from 61 patients (  = 34 placebo,  = 27 azithromycin). Azithromycin did not affect bacterial load (  = 0.37) but did significantly decrease Faith's phylogenetic diversity (  = 0.026) and load (  < 0.0001). Azithromycin did not significantly affect levels of , , , or . Of the 89 antibiotic resistance genes detected, five macrolide resistance genes and two tetracycline resistance genes were increased significantly. In patients with persistent uncontrolled asthma, azithromycin reduced airway 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.