In vitro activity and synergy of bismuth thiols and tobramycin against Burkholderia cepacia complex

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ObjectivesTo determine the susceptibility of Burkholderia multivorans and Burkholderia cenocepacia to bismuth-thiols (BTs), and to examine the synergistic effects of tobramycin and subinhibitory concentrations of BTs against these organisms.MethodsThe susceptibilities of 25 clinical isolates each of B. multivorans and B. cenocepacia to six BTs were measured by broth dilution in accordance with NCCLS protocols. Ten strains were selected to evaluate the antimicrobial interaction between BTs and tobramycin. Fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) indices were calculated to assess synergy.ResultsB. multivorans and B. cenocepacia showed a wide range of susceptibilities to BTs. Bismuth ethanedithiol (BisEDT) was one of the more potent BTs against these organisms (MIC50 7.8 µM), and was selected for synergy studies. Selected strains were highly resistant to tobramycin. The addition of subinhibitory concentrations of BisEDT (2 µM) reduced the MIC and MBC of tobramycin against all strains, achieving synergy in many instances. The FIC index was in the range 0.28–0.66 and the FBC in the range 0.12–0.85. Most strains became susceptible to tobramycin at clinically achievable concentrations in the presence of non-toxic BisEDT levels.ConclusionsTreatment with subinhibitory BisEDT and tobramycin reduces the MICs and MBCs for B. multivorans and B. cenocepacia. BTs may represent an important adjunctive therapy for resistant Burkholderia cepacia complex.

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