{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:18:42Z","timestamp":1790338722820,"version":"4.1.0"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Azithromycin (AZM) is a 15-membered-ring macrolide that presents a broad-spectrum antimicrobial activity against Gram-positive bacteria and atypical microorganisms but suffers from a poor diffusion across the outer-membrane of Gram-negative bacilli, including<jats:italic>Pseudomonas aeruginosa<\/jats:italic>(PA). However, AZM has demonstrated clinical benefits in patients suffering from chronic PA respiratory infections, especially cystic fibrosis patients. Since the rise of multidrug-resistant PA has led to a growing need for new therapeutic options, this macrolide has been proposed as an adjunctive therapy. Clinical trials assessing AZM in PA acute pneumonia are scarce. However, a careful examination of the available literature provides good rationales for its use in that context. In fact, 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. Furthermore, growing evidence supports a downregulation of PA virulence dependent on direct interaction with the ribosomes, and based on the modulation of several key regulators from the Quorum Sensing network. First highlighted<jats:italic>in vitro<\/jats:italic>, these interesting properties of AZM have subsequently been confirmed in the animal models. In this review, we systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects.<jats:italic>In vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.<\/jats:p>","DOI":"10.3389\/fmicb.2021.642541","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T07:00:01Z","timestamp":1615878001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?"],"prefix":"10.3389","volume":"12","author":[{"given":"Anne-Ga\u00eblle","family":"Leroy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyne","family":"Caillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Caroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Broquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Corvec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Asehnoune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Roquilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Cr\u00e9met","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1093\/jac\/38.1.81","article-title":"Comparison of various macrolides on stimulation of human neutrophil degranulation in vitro","volume":"38","author":"Abdelghaffar","year":"1996","journal-title":"J. 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