Azithromycin Attenuates Lung Inflammation in a Mouse Model of Ventilator-Associated Pneumonia by Multidrug-Resistant Acinetobacter baumannii

Abstract

c; Global COE Program, Nagasaki University, Nagasaki, Japan d 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.

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

“…AZM prevents the progression of lung inflammation in Acinetobacter baumannii-infected mice, without having an antimicrobial effect (71), and alters the macrophage phenotype and pulmonary compartmentalization during P. aeruginosa lung infection (72). Moreover, CLR displays efficacy against an intubation model of induced pneumonia caused by a CLR-resistant NTHI strain in mice, with reductions of bacterial loads and inflammation in CLRtreated animals (45).…”

Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model

“…Previous studies reported that the intestine in perioperative patients may serve as a hotbed for hospital infections and is the main site for the colonization and growth of MDRAb (7,27,28). Animal experimental MDRAb infection models include those for pneumonia (29,30), femoral region infection (31), burns (32), sepsis (33), severe diabetes (34), and infectious endophthalmitis (35); however, to our knowledge, no animal model currently exists for intestinal infections. In the in- …”

The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection

“…The importance of early antibiotic treatment during the course of infection and modulation of the inflammatory response are also illustrated in the model used in this study. In recent years, macrolides have caught increasing attention as anti-inflammatory agents, and several modes of action have been reported to explain these properties, including reduced production of proinflammatory cytokines, inhibited generation of reactive oxygen species (ROS), and increased neutrophil apoptosis (29)(30)(31)(32)(33)(34)(35). The development of novel erythromycin-derived macrolides such as EM703, targeting only inflammation and lacking unwanted side effects such as antibacterial activity and gastrointestinal motility-stimulating activity, make this therapeutic strategy more attractive.…”