Leroy Anne-Gaëlle, Caillon Jocelyne, Caroff Nathalie, Broquet Alexis, Corvec Stéphane, Asehnoune Karim, Roquilly Antoine, Crémet Lise
Laboratoire EA 3826 "Thérapeutiques cliniques et expérimentales des infections", IRS2-Nantes Biotech, Université de Nantes, Nantes, France.
CHU de Nantes, Service de Bactériologie-Hygiène hospitalière, Nantes Université, Nantes, France.
Front Microbiol. 2021 Mar 16;12:642541. doi: 10.3389/fmicb.2021.642541. eCollection 2021.
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 (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 , 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. and studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.
阿奇霉素（AZM）是一种15元环大环内酯类抗生素，对革兰氏阳性菌和非典型微生物具有广谱抗菌活性，但在穿过革兰氏阴性杆菌（包括铜绿假单胞菌）的外膜时扩散性较差。然而，阿奇霉素已在患有慢性铜绿假单胞菌呼吸道感染的患者，尤其是囊性纤维化患者中显示出临床益处。由于多重耐药铜绿假单胞菌的出现导致对新治疗选择的需求不断增加，这种大环内酯类抗生素已被提议作为辅助治疗。评估阿奇霉素在铜绿假单胞菌急性肺炎中作用的临床试验很少。然而，仔细查阅现有文献可为其在这种情况下的使用提供充分的理论依据。事实上，14元和15元环大环内酯类抗生素已显示出免疫调节和免疫抑制作用，这在急性疾病的管理中可能具有重要意义。此外，越来越多的证据支持铜绿假单胞菌毒力的下调依赖于与核糖体的直接相互作用，并基于群体感应网络中几个关键调节因子的调节。首先被强调的是，阿奇霉素的这些有趣特性随后在动物模型中得到了证实。在本综述中，我们系统地分析了有关阿奇霉素免疫调节和抗铜绿假单胞菌作用的文献。回顾了体外和体内研究以及临床试验，以寻找阿奇霉素在铜绿假单胞菌急性肺炎中使用的理论依据。
