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Updated: May 10, 2026

Murine Oropharyngeal Aspiration Model of Ventilator-associated and Hospital-acquired Bacterial Pneumonia
Published on: June 28, 2018
Azithromycin attenuates lung inflammation in a mouse model of ventilator-associated pneumonia by multidrug-resistant
Koichi Yamada1, Katsunori Yanagihara, Norihito Kaku
1Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
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.
Insights
Azithromycin (AZM) did not kill multidrug-resistant Acinetobacter baumannii causing pneumonia in mice. However, AZM reduced inflammation and improved survival, suggesting a potential anti-inflammatory role in treating ventilator-associated pneumonia (VAP).
Area of Science:
- Infectious Diseases
- Pulmonology
- Pharmacology
Background:
- Acinetobacter baumannii is a primary cause of ventilator-associated pneumonia (VAP), often exhibiting multidrug resistance (MDRAB) and high mortality.
- The efficacy of macrolides, such as azithromycin (AZM), against A. baumannii remains largely unexplored.
Purpose of the Study:
- To investigate the efficacy of azithromycin (AZM) in a mouse model of VAP caused by multidrug-resistant Acinetobacter baumannii (MDRAB).
- To evaluate the direct antimicrobial effects and the anti-inflammatory properties of AZM in this VAP model.
Main Methods:
- A mouse model of VAP was established using a plastic tube in the bronchus, followed by inoculation with MDRAB.
- Mice received subcutaneous azithromycin (10 and 100 mg/kg) or phosphate-buffered saline (control) daily.
- Survival rates, bacterial loads in lungs and bronchoalveolar lavage fluid (BALF), histopathological lung changes, and BALF inflammatory markers were assessed.
Main Results:
- Azithromycin treatment significantly increased survival rates compared to the control group (P < 0.05).
- No direct antimicrobial effect of AZM against A. baumannii was observed.
- Histopathological analysis revealed prevention of lung inflammation progression in AZM-treated groups, with significantly reduced total cell and neutrophil counts, and lower cytokine levels in BALF (P < 0.05).
Conclusions:
- Azithromycin demonstrated significant anti-inflammatory effects in a mouse model of VAP caused by MDRAB.
- Despite lacking direct antimicrobial activity, AZM's ability to mitigate lung inflammation and improve survival suggests a potential therapeutic role in managing VAP due to MDRAB.
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