Immunotherapy markedly increases the effectiveness of antimicrobial therapy for treatment of Burkholderia pseudomallei infection

Katie L. Propst, Ryan M. Troyer, Lisa M. Kellihan, Herbert P. Schweizer, Steven W. Dow

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Burkholderia pseudomallei is a soil bacterium that is endemic in southeast Asia and northern Australia and that can cause both acutely lethal pneumonia and chronic systemic infections in humans. The effective treatment of infection with B. pseudomallei requires rapid diagnosis and prolonged treatment with high doses of antimicrobials, and even with appropriate antibiotic therapy, patient relapses are common. Thus, new approaches to the treatment of B. pseudomallei infections are needed. In the present study, we asked whether active immunotherapy with gamma interferon (IFN-γ), a key cytokine regulating the intracellular replication of B. pseudomallei, could increase the effectiveness of conventional antimicrobial therapy for B. pseudomallei infection. Macrophage infection assays and in vivo pulmonary challenge models were used to assess the inhibitory effects of combined treatment with IFN-γ and ceftazidime on B. pseudomallei infection. We found that treatment with even very low doses of IFN-γ and ceftazidime elicited strong synergistic inhibition of B. pseudomallei growth within infected macrophages. In vivo, active immunotherapy markedly potentiated the effectiveness of low-dose ceftazidime therapy for the treatment of infected mice in a pulmonary challenge model of B. pseudomallei. Combined treatment was associated with a significant reduction in the bacterial burden and a significant lessening of bacterial dissemination. We concluded, therefore, that immunotherapy with either endogenous or exogenous IFN-γ could significantly increase the effectiveness of conventional antimicrobial therapy for the treatment of acute B. pseudomallei infection.

Original languageEnglish (US)
Pages (from-to)1785-1792
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume54
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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