NDLI: Immunotherapy Markedly Increases the Effectiveness of Antimicrobial Therapy for Treatment of Burkholderia pseudomallei Infection▿ †

Content Provider	PubMed Central
Author	Propst, Katie L. Troyer, Ryan M. Kellihan, Lisa M. Schweizer, Herbert P. Dow, Steven W.
Copyright Year	2010
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.
Related Links	http://dx.doi.org/10.1128/aac.01513-09
Ending Page	1792
Page Count	8
Starting Page	1785
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	5
Volume Number	54
Language	English
Publisher	American Society for Microbiology (ASM)
Publisher Date	2010-05-01
Access Restriction	Open
Rights Holder	American Society for Microbiology (ASM)
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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