Anti-Infective Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Infective Agents)

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Burkholderia pseudomallei - Antimicrobial Susceptibility Testing and Alternative Models of Predicting Clinical Efficacy.

Author(s): Robert Norton.

Abstract:

Melioidosis is caused by the gram-negative bacterium Burkholderia pseudomallei. The disease can present with a diverse range of clinical manifestations and is endemic in northern Australia and Southeast Asia. There is a dramatic increase in clinical cases during the wet season and mortality rates remain as high as 70% in some endemic areas. This is despite current optimal treatment with ceftazidime or meropenem, with trimethoprim-sulfamethoxazole.. This highlights the need for studies into novel antimicrobials or adjunctive therapies. There are currently no CLSI disc diffusion susceptibility criteria for this organism. A comparative study looking at methods of susceptibility testing for B. pseudomallei showed that an MIC based method is required to test susceptibility against trimethoprim-sulfamethoxazole. CLSI MIC breakpoints for this organism are available. In-vitro susceptibility testing to alternative antimicrobials has also been done for ertapenem, moxifloxacin and tigecycline. Recently, a BALB/c mouse model of melioidosis has been used to investigate strategies for antimicrobial therapy. Combination therapy with ceftazidime and trimethoprim-sulfamethoxazole has been found to be most efficacious. The use of granulocyte colony stimulating factor as adjunctive therapy has also been studied and shown to be of little value in this model. Similar studies are planned for the novel glycylcycline tigecycline. An Acanthamoeba intracellular, broth microdilution, model for B. pseudomallei has also been developed. This showed elevated MICs to both meropenem and ceftazidime when compared with standard MIC determination. Both these alternative models provide us with a unique opportunity to further our knowledge in several key aspects of an important tropical infectious disease.

Keywords: Melioidosis, Burkholderia pseudomallei, susceptibility testing, animal model

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Article Details

VOLUME: 6
ISSUE: 2
Year: 2007
Page: [83 - 88]
Pages: 6
DOI: 10.2174/187152107780361661
Price: $58