This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Rodriguez-Tudela, J. L.
Right arrow Articles by Cuenca-Estrella, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodriguez-Tudela, J. L.
Right arrow Articles by Cuenca-Estrella, M.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2008, p. 2468-2472, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00156-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Epidemiological Cutoffs and Cross-Resistance to Azole Drugs in Aspergillus fumigatus{triangledown} ,{dagger}

Juan Luis Rodriguez-Tudela,* Laura Alcazar-Fuoli, Emilia Mellado, Ana Alastruey-Izquierdo, Araceli Monzon, and Manuel Cuenca-Estrella

Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain

Received 4 February 2008/ Returned for modification 22 March 2008/ Accepted 7 May 2008

Antifungal susceptibility testing of molds has been standardized in Europe and in the United States. Aspergillus fumigatus strains with resistance to azole drugs have recently been detected and the underlying molecular mechanisms of resistance characterized. Three hundred and ninety-three isolates, including 32 itraconazole-resistant strains, were used to define wild-type populations, epidemiological cutoffs, and cross-resistance between azole drugs. The epidemiological cutoff for itraconazole, voriconazole, and ravuconazole for the wild-type populations of A. fumigatus was ≤1 mg/liter. For posaconazole, the epidemiological cutoff was ≤0.25 mg/liter. Up till now, isolates susceptible to itraconazole have not yet displayed resistance to other azole drugs. Cross-resistance between azole drugs depends on specific mutations in cyp51A. Thus, a substitution of glycine in position 54 of Cyp51A confers cross-resistance between itraconazole and posaconazole. A substitution of methionine at position 220 or a duplication in tandem of a 34-bp fragment in the cyp51A promoter combined with a substitution of leucine at position 98 for histidine confers cross-resistance to all azole drugs tested. The results obtained in this study will help to develop clinical breakpoints for azole drugs and A. fumigatus.

* Corresponding author. Mailing address: Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Ctra Majadahonda Pozuelo km 2, 28220 Majadahonda, Spain. Phone: 34 91 822 3919. E-mail: jlrtudela{at}isciii.es

{triangledown} Published ahead of print on 12 May 2008.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, July 2008, p. 2468-2472, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00156-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Araujo, R., Espinel-Ingroff, A. (2009). Comparison of Assessment of Oxygen Consumption, Etest, and CLSI M38-A2 Broth Microdilution Methods for Evaluation of the Susceptibility of Aspergillus fumigatus to Posaconazole. Antimicrob. Agents Chemother. 53: 4921-4923 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Ghannoum, M. A., Rex, J. H., Alexander, B. D., Andes, D., Brown, S. D., Chaturvedi, V., Espinel-Ingroff, A., Fowler, C. L., Johnson, E. M., Knapp, C. C., Motyl, M. R., Ostrosky-Zeichner, L., Sheehan, D. J., Walsh, T. J., for the Clinical and Laboratory Standards Institut, (2009). Wild-Type MIC Distribution and Epidemiological Cutoff Values for Aspergillus fumigatus and Three Triazoles as Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Methods. J. Clin. Microbiol. 47: 3142-3146 [Abstract] [Full Text]  
  • Baddley, J. W., Marr, K. A., Andes, D. R., Walsh, T. J., Kauffman, C. A., Kontoyiannis, D. P., Ito, J. I., Balajee, S. A., Pappas, P. G., Moser, S. A. (2009). Patterns of Susceptibility of Aspergillus Isolates Recovered from Patients Enrolled in the Transplant-Associated Infection Surveillance Network. J. Clin. Microbiol. 47: 3271-3275 [Abstract] [Full Text]  
  • Beernaert, L. A., Pasmans, F., Van Waeyenberghe, L., Dorrestein, G. M., Verstappen, F., Vercammen, F., Haesebrouck, F., Martel, A. (2009). Avian Aspergillus fumigatus Strains Resistant to both Itraconazole and Voriconazole. Antimicrob. Agents Chemother. 53: 2199-2201 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Boyken, L., Rice, C., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2008). In Vitro Survey of Triazole Cross-Resistance among More than 700 Clinical Isolates of Aspergillus Species. J. Clin. Microbiol. 46: 2568-2572 [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»