Immunotherapy Markedly Increases the Effectiveness of Antimicrobial Therapy for Treatment ofBurkholderia pseudomalleiInfection

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 withB. 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 ofB. 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 ofB. pseudomallei , could increase the effectiveness of conventional antimicrobial therapy forB. pseudomallei infection. Macrophage infection assays andin vivo pulmonary challenge models were used to assess the inhibitory effects of combined treatment with IFN-γ and ceftazidime onB. pseudomallei infection. We found that treatment with even very low doses of IFN-γ and ceftazidime elicited strong synergistic inhibition ofB. 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 ofB. 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 acuteB. pseudomallei infection.