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.

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.