Combination therapy with ampicillin and azithromycin in an experimental pneumococcal pneumonia is bactericidal and effective in down regulating inflammation in mice

Arnab Majhi, Kiran Kundu, Rana Adhikary, Madhubanti Banerjee, Sayantika Mahanti, Anirban Basu, Biswadev Bishayi

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Objectives. Emergence of multidrug resistance among Streptococcus pneumoniae (SP), has limited the available options used to treat infections caused by this organism. The objective of this study was to compare the role of monotherapy and combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating bacterial burden and down regulating lung inflammation in a murine experimental pneumococcal infection model. Methods. Balb/C mice were infected with 10§ssup§6§esup§ CFU of SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50 mg/kg) either alone or in combination was initiated 18 h post infection, animals were sacrificed from 0 - 6 h after initiation of treatment. AMP and AZM were quantified in serum by microbiological assay. Levels of TNF-α, IFN-γ IL-6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell count in broncho alveolar lavage fluid, COX-2 and histopathological changes in lungs were estimated. Results: Combination therapy down regulated lung inflammation and accelerated bacterial clearance. This approach also significantly decreased TNF-α, IFN-γ, IL-6 and increased IL-10 level in serum and lungs along with decreased myeloperoxidase, pulmonary vascular permeability, inflammatory cell numbers and COX-2 levels in lungs. Conclusions: Combinatorial therapy resulted in comparable bactericidal activity against the multi-drug resistant isolate and may represent an alternative dosing strategy, which may help to alleviate problems with pneumococcal pneumonia.

Original languageEnglish
Article number5
JournalJournal of Inflammation
Volume11
Issue number1
DOIs
StatePublished - 24 Feb 2014
Externally publishedYes

Keywords

  • Ampicillin
  • Azihromycin
  • Combination therapy
  • Inflammation
  • Multiple drug resistance
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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