This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Te Dorsthorst, D. T. A.
Right arrow Articles by Mouton, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Te Dorsthorst, D. T. A.
Right arrow Articles by Mouton, J. W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2004, p. 2007-2013, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2007-2013.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Interactions between Amphotericin B, Itraconazole, and Flucytosine against 21 Clinical Aspergillus Isolates Determined by Two Drug Interaction Models

D. T. A. Te Dorsthorst,1,2,3 P. E. Verweij,2,3 J. F. G. M. Meis,1 N. C. Punt,4 and J. W. Mouton1*

Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital Nijmegen,1 Department of Medical Microbiology, University Medical Center Nijmegen,2 Nijmegen University Center for Infectious Diseases, Nijmegen,3 Medimatics, Maastricht, The Netherlands4

Received 10 July 2003/ Returned for modification 14 July 2003/ Accepted 21 February 2004

Combination therapy of flucytosine (5FC) with other antifungal agents could be of use for the treatment of invasive aspergillosis. However, interpretation of the results of in vitro interactions is problematic. The fractional inhibitory concentration (FIC) index is the most commonly used method, but it has several major drawbacks in characterizing antifungal drug interaction. Alternatively, a response surface approach using the concentration-effect relationship over the whole concentration range instead of just the MIC can be used. We determined the in vitro interactions between amphotericin B (AMB), itraconazole, and 5FC against 21 Aspergillus isolates with a broth microdilution checkerboard method that employs the dye MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. FIC indices based on three different MIC endpoints (MIC-0, MIC-1, and MIC-2) and the interaction coefficient alpha were determined, the latter by estimation from the response surface approach described by Greco et al. (W. R. Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995). The value obtained for the FIC index was found to be dependent on the MIC endpoint used and could be either synergistic, indifferent, or antagonistic. The response surface approach gave more consistent results. Of the three combinations tested, the AMB-5FC combination was the most potent in vitro against Aspergillus spp. We conclude that the use of the response surface approach for the interpretation of in vitro interaction studies of antifungals may be helpful in order to predict the nature and intensity of the drug interaction. However, the correlation of these results with clinical outcome remains difficult and needs to be further investigated.

* Corresponding author. Mailing address: Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Weg door Jonkerbos 100, 6532 SZ Nijmegen, The Netherlands. Phone: 31-(0)24-3657514. Fax: 31-(0)24-3657516. E-mail: mouton{at}cwz.nl.

Antimicrobial Agents and Chemotherapy, June 2004, p. 2007-2013, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2007-2013.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nett, J. E., Guite, K. M., Ringeisen, A., Holoyda, K. A., Andes, D. R. (2008). Reduced Biocide Susceptibility in Candida albicans Biofilms. Antimicrob. Agents Chemother. 52: 3411-3413 [Abstract] [Full Text]  
  • Guo, Q., Sun, S., Yu, J., Li, Y., Cao, L. (2008). Synergistic activity of azoles with amiodarone against clinically resistant Candida albicans tested by chequerboard and time-kill methods. J Med Microbiol 57: 457-462 [Abstract] [Full Text]  
  • Li, Y., Sun, S., Guo, Q., Ma, L., Shi, C., Su, L., Li, H. (2008). In vitro interaction between azoles and cyclosporin A against clinical isolates of Candida albicans determined by the chequerboard method and time-kill curves. J Antimicrob Chemother 61: 577-585 [Abstract] [Full Text]  
  • Sun, S., Li, Y., Guo, Q., Shi, C., Yu, J., Ma, L. (2008). In Vitro Interactions between Tacrolimus and Azoles against Candida albicans Determined by Different Methods. Antimicrob. Agents Chemother. 52: 409-417 [Abstract] [Full Text]  
  • Brun, Y. F., Dennis, C. G., Greco, W. R., Bernacki, R. J., Pera, P. J., Bushey, J. J., Youn, R. C., White, D. B., Segal, B. H. (2007). Modeling the Combination of Amphotericin B, Micafungin, and Nikkomycin Z against Aspergillus fumigatus In Vitro Using a Novel Response Surface Paradigm. Antimicrob. Agents Chemother. 51: 1804-1812 [Abstract] [Full Text]  
  • Nett, J., Lincoln, L., Marchillo, K., Massey, R., Holoyda, K., Hoff, B., VanHandel, M., Andes, D. (2007). Putative Role of {beta}-1,3 Glucans in Candida albicans Biofilm Resistance. Antimicrob. Agents Chemother. 51: 510-520 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»