Macrolide-treated Pseudomonas aeruginosa induces paradoxical host responses in the lungs of mice and a high mortality rate

J Antimicrob Chemother. 2002 Jul;50(1):59-66. doi: 10.1093/jac/dkf048.

Abstract

Objective: Accumulating data have demonstrated that macrolide antibiotics suppress Pseudomonas aeruginosa virulence, which may explain the efficacy of macrolides in clinical settings. We examined the virulence of macrolide-treated bacteria in vivo.

Methods: P. aeruginosa PAO-1 was grown for 24 h on agar containing sub-MIC antibiotics, and then mice were challenged intranasally with 10(7) cfu of bacteria.

Results and conclusions: The mortality rate of mice inoculated with bacteria grown in the presence of clarithromycin (10 mg/L), erythromycin (10 mg/L) or azithromycin (5 mg/L) was 80%, 80% and 100%, respectively. In contrast, none of the mice inoculated with non-treated bacteria or bacteria treated with other antibiotics died. Lung weight and protein concentration in bronchoalveolar lavage fluid (BALF) were significantly higher in the clarithromycin group between 3 and 9 h. Moreover, we detected higher levels of tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in the BALF of these mice. These data demonstrate that macrolide-treated P. aeruginosa induced paradoxically strong responses, such as elevation of TNF-alpha, NO and permeability in the lungs.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Lung / immunology*
  • Lung / microbiology
  • Lung / pathology
  • Macrolides
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / immunology
  • Pancreatic Elastase / immunology
  • Pancreatic Elastase / metabolism
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / microbiology*
  • Pneumonia, Bacterial / pathology
  • Pseudomonas Infections / immunology
  • Pseudomonas Infections / microbiology*
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / isolation & purification
  • Pseudomonas aeruginosa / pathogenicity*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology
  • Virulence

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Pancreatic Elastase