Affiliation:
1. Department of Microbiology, Immunology, and Pathology, Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research, Colorado State University, Ft. Collins, Colorado 80523
Abstract
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
40 articles.
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