Abstract
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 Pseudomonas aeruginosa (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 in vitro, 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. In vitro and in vivo studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.
Highlights
Isolated from Streptomyces species, macrolide antibiotics are composed of a central macrocyclic lactone ring of 14, 15, or 16 atoms of carbon to which various sugar substituents are attached (Retsema and Fu, 2001)
Pseudomonas aeruginosa QS network relies on three interconnected systems: two acyl-homoserine lactones (AHL) QS systems, LasI-LasR and RhlI-RhlR, and a third system relying on the production of alkyl-quinolones (AQ) named the Pseudomonas quinolone signal (PQS) system (Jimenez et al, 2012; García-Reyes et al, 2020)
We found only one study that assessed the effects of a modified macrolide, EM703, lacking antibiotic activity, as an adjunct anti-inflammatory treatment in association with levofloxacin, in a Pseudomonas aeruginosa (PA) acute pneumonia murine model (Kasetty et al, 2017)
Summary
Anne-Gaëlle Leroy 1,2*, Jocelyne Caillon 1,2, Nathalie Caroff 1, Alexis Broquet 1, Stéphane Corvec 2,3, Karim Asehnoune 1,4, Antoine Roquilly 1,4 and Lise Crémet 1,2. 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 Pseudomonas aeruginosa (PA). 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. 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. We systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects. In vitro and in vivo studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
