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Combination antimicrobial therapy of acute Burkholderia pseudomallei infection in a mouse model
G C Ulett1, R E Norton, R G Hirst
1Department of Microbiology and Immunology, James Cook University, Townsville, Queensland, Australia.
Abstract:
Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic in tropical and subtropical regions of South-East Asia and Northern Australia. Antimicrobial therapy regimens for treatment of acute septicemic melioidosis are of variable efficacy. Ceftazidime is the current antibiotic of choice and is commonly administered with other agents such as cotrimoxazole or doxycycline. The emergence of resistant strains of B. pseudomallei and the persistence of high mortality rates prompted the present study. Using an established mouse model of acute disseminated B. pseudomallei infection, we compared the efficacy of ceftazidime versus cefpirome in combination with cotrimoxazole or chloramphenicol therapy in vivo. Control mice that were infected but did not receive antibiotic therapy died within 96 hours of infection. No deaths occurred in treatment groups receiving either cephalosporin or cotrimoxazole, despite the demonstrated resistance of B. pseudomallei to cotrimoxazole in vitro. The mortality rate in treatment groups receiving either cephalosporin and chloramphenicol was 66%. These results demonstrate a comparable level of efficacy between ceftazidime and cefpirome for treatment of acute B. pseudomallei infection in mice.
Insights
Ceftazidime and cefpirome show comparable efficacy in treating B. pseudomallei infections in mice. This study compared cephalosporins with other antibiotics for melioidosis treatment.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is prevalent in tropical/subtropical areas.
- Current antimicrobial treatments for septicemic melioidosis have variable efficacy.
- Emerging B. pseudomallei resistance and high mortality necessitate new therapeutic strategies.
Purpose of the Study:
- To compare the in vivo efficacy of ceftazidime and cefpirome against B. pseudomallei.
- To evaluate combinations of cephalosporins with cotrimoxazole or chloramphenicol.
Main Methods:
- An established mouse model of acute disseminated B. pseudomallei infection was utilized.
- Mice received treatments including ceftazidime, cefpirome, cotrimoxazole, or chloramphenicol, alone or in combination.
- Control groups received no antibiotic therapy.
Main Results:
- All control mice died within 96 hours.
- No deaths were observed in groups treated with either cephalosporin or cotrimoxazole, even with in vitro resistance.
- Mortality rates in groups receiving cephalosporin plus chloramphenicol were 66%.
Conclusions:
- Ceftazidime and cefpirome exhibit comparable efficacy in treating acute B. pseudomallei infections in a murine model.
- Combination therapy with cephalosporins and chloramphenicol resulted in a 66% mortality rate.
- Further research into effective antimicrobial regimens for melioidosis is warranted.
