Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

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.

Prevalence of Fungal and Bacterial Co-Infection in Pulmonary Fungal Infections: A Metagenomic Next Generation Sequencing-Based Study

“…For fungal and bacterial co-infections, 17 types of bacteria were identified, almost all of which were hospital-associated pathogens. P. aeruginosa , the most commonly isolated bacterial species in this study, is a gram-negative opportunistic pathogen existing in diverse environmental settings that harbors multi-drug resistance and poses serious therapeutic challenges ( Lister et al., 2009 ; Leroy et al., 2021 ). Interestingly, four strains of Mycobacterium tuberculosis were isolated in pulmonary bacterial and fungal co-infection, of which three were co-infected with Aspergillus and one with Rhizopus .…”

Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse model

“…In cystic fibrosis with Pseudomonas aeruginosa infection, long-term azithromycin therapy reduces exacerbations by inhibiting virulence factors in P . aeruginosa [ 2 – 5 ]. Macrolides have also been used in non–cystic fibrosis bronchiectasis, diffuse panbronchiolitis, chronic obstructive pulmonary disease, chronic rhinosinusitis, and asthma [ 1 , 2 , 6 ].…”

“…Systemic inflammation associated with ARDS is commonly treated for up to 3 weeks with corticosteroids such as methylprednisolone or dexamethasone [ 10 ]. Macrolide treatment has also been shown to improve clinical outcomes in patients with ARDS, accompanied by evidence that these effects resulted from the immunomodulatory, not the antimicrobial, effects of the macrolides [ 5 , 11 ]. Lipopolysaccharide (LPS) administration can induce pathologic and biological changes similar to those seen in ARDS, including neutrophilic infiltration and increased intrapulmonary cytokines, which have been extensively studied in experimental models of acute lung injury [ 12 ].…”

Excipient-Free Inhalable Microparticles of Azithromycin Produced by Electrospray: A Novel Approach to Direct Pulmonary Delivery of Antibiotics

“…This accumulation results in a long half-life (68-79 h) of the drug. Among its characteristics, the excellent penetration in lung tissues and the sustained drug concentration by tissues and cells, makes the azithromycin a good candidate for the treatment of respiratory infections [12].…”

“…It presents activity against both Gram-negative and Gram-positive pathogens [14], such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria are responsible for several chronic lung infections, especially in patients with impaired immune system or who are suffering from damaged mucosa such as cystic fibrosis (CF) disease [12,15]. As a consequence of these lung infections, a further deterioration of lung function appears.…”