Immunotherapy markedly increases the effectiveness of antimicrobial therapy for treatment of Burkholderia pseudomallei infection
| Autor: | Ryan M. Troyer, Steven W. Dow, Lisa M. Kellihan, Katie L. Propst, Herbert P. Schweizer |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Melioidosis
Burkholderia pseudomallei medicine.drug_class medicine.medical_treatment Antibiotics Ceftazidime Active immunotherapy Biology Microbiology Avian Proteins Interferon-gamma Mice Pharmacotherapy medicine Animals Immunologic Factors Experimental Therapeutics Pharmacology (medical) Letters to the Editor Pharmacology Mice Inbred BALB C Macrophages Drug Synergism Immunotherapy bacterial infections and mycoses Antimicrobial biology.organism_classification medicine.disease Anti-Bacterial Agents Disease Models Animal Infectious Diseases Immunology bacteria Cytokines Drug Therapy Combination Female Cell Division medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 54(5) |
| ISSN: | 1098-6596 |
| Popis: | Burkholderia pseudomalleiis 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. pseudomalleirequires 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. pseudomalleiinfections 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. pseudomalleiinfection. Macrophage infection assays andin vivopulmonary challenge models were used to assess the inhibitory effects of combined treatment with IFN-γ and ceftazidime onB. pseudomalleiinfection. We found that treatment with even very low doses of IFN-γ and ceftazidime elicited strong synergistic inhibition ofB. pseudomalleigrowth 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. pseudomalleiinfection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|