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 Afeltra, J.
Right arrow Articles by Verweij, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Afeltra, J.
Right arrow Articles by Verweij, P. E.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2004, p. 1335-1343, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1335-1343.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Potent Synergistic In Vitro Interaction between Nonantimicrobial Membrane-Active Compounds and Itraconazole against Clinical Isolates of Aspergillus fumigatus Resistant to Itraconazole

Javier Afeltra,1,2 Roxana G. Vitale,1,2 Johan W. Mouton,3 and Paul E. Verweij1,2*

Department of Medical Microbiology, University Medical Center Nijmegen,1 Department of Medical Microbiology and Infectious Diseases, Canisius Wilhemina Hospital,3 Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands2

Received 30 June 2003/ Returned for modification 24 August 2003/ Accepted 12 November 2003

To develop new approaches for the treatment of invasive infections caused by Aspergillus fumigatus, the in vitro interactions between itraconazole (ITZ) and seven different nonantimicrobial membrane-active compounds—amiodarone (AMD), amiloride, lidocaine, lansoprazole (LAN), nifedipine (NIF), verapamil, and fluphenazine—against seven ITZ-susceptible and seven ITZ-resistant (ITZ-R) strains were evaluated by the checkerboard microdilution method based on National Committee for Clinical Laboratory Standards M-38A guidelines. The nature and the intensity of the interactions were assessed by a nonparametric approach (fractional inhibitory concentration [FIC] index model), a fully parametric response surface approach (Greco model) of the Loewe additivity no-interaction theory, and the nonparametric (Prichard model) and semiparametric response surface approaches of the Bliss independence (BI) no-interaction theory. Statistically significant synergy was found for the combination of ITZ and AMD and the combination of LAN and NIF, although with different intensities against ITZ-R strains. The FIC index values ranged from 1 to 0.02 for ITZ-AMD, 0.53 to 0.04 for ITZ-LAN, and 0.28 to 0.06 for ITZ-NIF. By use of the BI-based model, the strongest synergy was found for the combination of ITZ with AMD, followed by the combination of ITZ and NIF. The parametric models could not be fit adequately because most of the drugs alone did not show any effect and, thus, no sigmoid dose-response. In general, the combination of ITZ with calcium pump blockers displayed in vitro synergistic activity, primarily against ITZ-R strains, and warrants further investigation.

* Corresponding author. Mailing address: Department of Medical Microbiology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 31-24-3614356. Fax: 31-24-3540216. E-mail: p.verweij{at}mmb.umcn.nl.

Antimicrobial Agents and Chemotherapy, April 2004, p. 1335-1343, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1335-1343.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Maresova, L., Muend, S., Zhang, Y.-Q., Sychrova, H., Rao, R. (2009). Membrane Hyperpolarization Drives Cation Influx and Fungicidal Activity of Amiodarone. J. Biol. Chem. 284: 2795-2802 [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]  
  • 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]  
  • Garcia-Effron, G., Mellado, E., Gomez-Lopez, A., Alcazar-Fuoli, L., Cuenca-Estrella, M., Rodriguez-Tudela, J. L. (2005). Differences in Interactions between Azole Drugs Related to Modifications in the 14-{alpha} Sterol Demethylase Gene (cyp51A) of Aspergillus fumigatus. Antimicrob. Agents Chemother. 49: 2119-2121 [Abstract] [Full Text]  
  • Cuenca-Estrella, M. (2004). Combinations of antifungal agents in therapy-what value are they?. J Antimicrob Chemother 54: 854-869 [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»