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JAC Advance Access published online on October 29, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg471
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

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

Wilfredo G. Veloira 1 , Philip Domenico 2 *, John J. LiPuma 3 , Jonathan M. Davis 1 , Ellen Gurzenda 4 , and Jeffrey A. Kazzaz 2

1 Department of Pediatrics (Pulmonary Medicine and Neonatology) and the CardioPulmonary Research Institute, Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, NY
2 Department of Medicine and the CardioPulmonary Research Institute, Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, NY
3 Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA
4 The CardioPulmonary Research Institute, Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, NY

* Corresponding author. E-mail: pdomenico{at}winthrop.org.

Received 10 June 2003 ; revised 11 September 2003 ; accepted 13 September 2003

Abstract

Objectives: To 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.

Methods: The 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.

Results: B. 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.

Conclusions: Treatment 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.

Keywords: cystic fibrosis, antibiotics, biofilms, bacterial polysaccharide, aminoglycosides
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