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A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
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Combination therapy with ampicillin and azithromycin in an experimental pneumococcal pneumonia is bactericidal and

Arnab Majhi, Kiran Kundu, Rana Adhikary

  • 1Department of Physiology, Immunology laboratory, University of Calcutta, University Colleges of Science and Technology, 92 APC Road, Calcutta 700009, West Bengal,India. biswadevbishayi4@gmail.com.

Journal of Inflammation (London, England)
|February 26, 2014
PubMed
Abstract

Insights

Combination therapy with ampicillin (AMP) and azithromycin (AZM) effectively reduced bacterial burden and lung inflammation in a murine model of Streptococcus pneumoniae infection. This approach offers a promising strategy for treating multidrug-resistant pneumococcal pneumonia.

Area of Science:

  • Microbiology and Immunology
  • Pharmacology
  • Infectious Diseases

Background:

  • Multidrug resistance in Streptococcus pneumoniae (SP) poses a significant challenge for treating bacterial infections.
  • Limited therapeutic options are available for infections caused by resistant SP strains.

Purpose of the Study:

  • To compare the efficacy of ampicillin (AMP) monotherapy versus combination therapy with azithromycin (AZM) in reducing bacterial load and lung inflammation.
  • To evaluate the impact of AMP and AZM, alone and in combination, on inflammatory markers and histopathological changes in a murine pneumococcal pneumonia model.

Main Methods:

  • Balb/C mice were infected with SP (10^6 CFU).
  • Treatments included intravenous AMP (200 mg/kg) and AZM (50 mg/kg) administered alone or in combination starting 18 hours post-infection.
  • Bacterial clearance, serum/lung cytokine levels (TNF-α, IFN-γ, IL-6, IL-10), myeloperoxidase, inflammatory cell counts, COX-2, and lung histology were assessed.

Main Results:

  • Combination therapy significantly reduced lung inflammation and accelerated bacterial clearance compared to monotherapy.
  • The combined treatment decreased pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6) and increased anti-inflammatory IL-10.
  • Key indicators of inflammation, including myeloperoxidase, inflammatory cell counts, and COX-2 levels in the lungs, were significantly reduced.

Conclusions:

  • Combination therapy demonstrated comparable bactericidal activity against multidrug-resistant SP isolates.
  • This therapeutic strategy may offer an alternative dosing regimen to manage pneumococcal pneumonia effectively.

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