title: Azithromycin attenuates lung inflammation in a mouse model of ventilator-associated pneumonia by multidrug-resistant Acinetobacter baumannii.
abstract: Acinetobacter baumannii is one of the main pathogens that cause ventilator-associated pneumonia (VAP) and is associated with a high rate of mortality. Little is known about the efficacy of macrolides against A. baumannii. In order to confirm the efficacy of azithromycin (AZM) against VAP caused by multidrug-resistant A. baumannii (MDRAB), we used a mouse model that mimics VAP by placement of a plastic tube in the bronchus. AZM (10 and 100 mg/kg of body weight) was administered subcutaneously every 24 h beginning at 3 h after inoculation. Phosphate-buffered saline was administered as the control. Survival was evaluated over 7 days. At 48 h postinfection, mice were sacrificed and the numbers of viable bacteria in lungs and bronchoalveolar lavage fluid were compared. Histopathological analysis of lung specimens was also performed. The treatment groups displayed significantly longer survival than the control group (P < 0.05). AZM did not have an antimicrobial effect. Histopathological examination of lung specimens indicated that the progression of lung inflammation was prevented in the AZM-treated groups. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in bronchoalveolar lavage fluid were significantly decreased (P < 0.05) in the AZM-treated groups. AZM may have a role for the treatment of VAP with MDRAB because of its anti-inflammatory effects.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamada
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Norihito
authors.initials: N
authors.lastname: Kaku
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Harada
authors.forename: Yohei
authors.initials: Y
authors.lastname: Migiyama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nagaoka
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Imamura
authors.forename: Taiga
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Izumikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kakeya
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000472:pathogenicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D058491:Bacterial Load; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D024901:Drug Resistance, Multiple, Bacterial; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D017963:Azithromycin