Epidemiological cut-off value of clinical isolates of Burkholderia pseudomallei from Northern Queensland to meropenem, ceftazidime, trimethoprim/sulfamethoxazole and doxycycline by the microbroth dilution method.

Abstract

Melioidosis is caused by the bacterium Burkholderia pseudomallei. The most common antibiotics used to treat melioidosis in Australia are meropenem, ceftazidime, trimethoprim/sulfamethoxazole (SXT) and doxycycline. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) do not provide standards for assessing the susceptibility of B. pseudomallei for these agents. The International Standards Organisation (ISO) microbroth dilution method is accepted both by the CLSI and EUCAST as the gold standard of antimicrobial susceptibility testing. Many previous studies of the susceptibility of B. pseudomallei used Etest or disk diffusion and presented the results as aggregate data. Etest and disk diffusion methods have not been standardised for B. pseudomallei and aggregate data cannot be used to determine an epidemiological cut-off value (ECOFF). An ECOFF is vital for the setting of clinical breakpoints. In this study, minimum inhibitory concentrations (MICs) of meropenem, ceftazidime, SXT and doxycycline were assessed by microbroth dilution for a library of 234 well characterised clinical isolates of B. pseudomallei from Northern Queensland, Australia. The resultant histograms and aggregate data represent the first MIC profile of a large library of B. pseudomallei that has been successfully produced using microbroth dilution. The MIC profiles can be used to contribute towards a determination of an ECOFF for this species for these agents, which will aid in the setting and refining of clinical breakpoints for the most important antimicrobials used to treat melioidosis.