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 Bennett, J. E.
Right arrow Articles by Marr, K. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bennett, J. E.
Right arrow Articles by Marr, K. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2004, p. 1773-1777, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1773-1777.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mechanism of Increased Fluconazole Resistance in Candida glabrata during Prophylaxis

John E. Bennett,1* Koichi Izumikawa,1 and Kieren A. Marr2

Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,1 Fred Hutchinson Cancer Research Center, University of Washington, School of Medicine, Seattle, Washington2

Received 29 September 2003/ Returned for modification 1 December 2003/ Accepted 8 January 2004

Candida glabrata can become resistant to fluconazole, causing persistent colonization and invasive infection during prolonged exposure to the drug. To determine the mechanism of resistance in this setting, weekly oropharyngeal cultures for C. glabrata were obtained over a 2-year period from hematopoietic stem cell transplant recipients who were receiving fluconazole prophylaxis. In 20 patients from whom at least two isolates of the same karyotype were obtained more than two weeks apart, fluconazole MICs doubled every 31 days on average. The mechanism of fluconazole resistance in isolates from the 14 of the 20 patients studied in whom MICs changed at least fourfold was studied. Cellular resistance was accompanied by increased drug efflux as measured by decreased accumulation of fluconazole and rhodamine 6G and increased abundance of transcripts from two drug transporters, CgCDR1 and PDH1. The rapidity and regularity of the rising resistance indicated that C. glabrata is able to upregulate drug efflux without losing the ability to maintain colonization.

* Corresponding author. Mailing address: National Institutes of Health, Clinical Center Room 11C304, Bethesda, MD 20892. Phone: (301) 496-3461. Fax: (301) 480-0050. E-mail: jbennett{at}niaid.nih.gov.

Antimicrobial Agents and Chemotherapy, May 2004, p. 1773-1777, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1773-1777.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pfaller, M. A., Messer, S. A., Hollis, R. J., Boyken, L., Tendolkar, S., Kroeger, J., Diekema, D. J. (2009). Variation in Susceptibility of Bloodstream Isolates of Candida glabrata to Fluconazole According to Patient Age and Geographic Location in the United States in 2001 to 2007. J. Clin. Microbiol. 47: 3185-3190 [Abstract] [Full Text]  
  • Sionov, E., Chang, Y. C., Garraffo, H. M., Kwon-Chung, K. J. (2009). Heteroresistance to Fluconazole in Cryptococcus neoformans Is Intrinsic and Associated with Virulence. Antimicrob. Agents Chemother. 53: 2804-2815 [Abstract] [Full Text]  
  • Posteraro, B., Martucci, R., La Sorda, M., Fiori, B., Sanglard, D., De Carolis, E., Florio, A. R., Fadda, G., Sanguinetti, M. (2009). Reliability of the Vitek 2 Yeast Susceptibility Test for Detection of In Vitro Resistance to Fluconazole and Voriconazole in Clinical Isolates of Candida albicans and Candida glabrata. J. Clin. Microbiol. 47: 1927-1930 [Abstract] [Full Text]  
  • Cannon, R. D., Lamping, E., Holmes, A. R., Niimi, K., Baret, P. V., Keniya, M. V., Tanabe, K., Niimi, M., Goffeau, A., Monk, B. C. (2009). Efflux-Mediated Antifungal Drug Resistance. Clin. Microbiol. Rev. 22: 291-321 [Abstract] [Full Text]  
  • Tumbarello, M., Sanguinetti, M., Trecarichi, E. M., La Sorda, M., Rossi, M., de Carolis, E., de Gaetano Donati, K., Fadda, G., Cauda, R., Posteraro, B. (2008). Fungaemia caused by Candida glabrata with reduced susceptibility to fluconazole due to altered gene expression: risk factors, antifungal treatment and outcome. J Antimicrob Chemother 62: 1379-1385 [Abstract] [Full Text]  
  • Ruan, S.-Y., Chu, C.-C., Hsueh, P.-R. (2008). In Vitro Susceptibilities of Invasive Isolates of Candida Species: Rapid Increase in Rates of Fluconazole Susceptible-Dose Dependent Candida glabrata Isolates. Antimicrob. Agents Chemother. 52: 2919-2922 [Abstract] [Full Text]  
  • Johnson, E. M. (2008). Issues in antifungal susceptibility testing. J Antimicrob Chemother 61: i13-i18 [Abstract] [Full Text]  
  • Chauhan, N., Kruppa, M., Calderone, R. (2007). The Ssk1p Response Regulator and Chk1p Histidine Kinase Mutants of Candida albicans Are Hypersensitive to Fluconazole and Voriconazole. Antimicrob. Agents Chemother. 51: 3747-3751 [Abstract] [Full Text]  
  • Shin, J. H., Chae, M. J., Song, J. W., Jung, S.-I., Cho, D., Kee, S. J., Kim, S. H., Shin, M. G., Suh, S. P., Ryang, D. W. (2007). Changes in Karyotype and Azole Susceptibility of Sequential Bloodstream Isolates from Patients with Candida glabrata Candidemia. J. Clin. Microbiol. 45: 2385-2391 [Abstract] [Full Text]  
  • Posteraro, B., Tumbarello, M., La Sorda, M., Spanu, T., Trecarichi, E. M., De Bernardis, F., Scoppettuolo, G., Sanguinetti, M., Fadda, G. (2006). Azole Resistance of Candida glabrata in a Case of Recurrent Fungemia.. J. Clin. Microbiol. 44: 3046-3047 [Abstract] [Full Text]  
  • Rogers, P. D., Vermitsky, J.-P., Edlind, T. D., Hilliard, G. M. (2006). Proteomic analysis of experimentally induced azole resistance in Candida glabrata. J Antimicrob Chemother 58: 434-438 [Abstract] [Full Text]  
  • Panackal, A. A., Gribskov, J. L., Staab, J. F., Kirby, K. A., Rinaldi, M., Marr, K. A. (2006). Clinical Significance of Azole Antifungal Drug Cross-Resistance in Candida glabrata.. J. Clin. Microbiol. 44: 1740-1743 [Abstract] [Full Text]  
  • Tsai, H.-F., Krol, A. A., Sarti, K. E., Bennett, J. E. (2006). Candida glabrata PDR1, a Transcriptional Regulator of a Pleiotropic Drug Resistance Network, Mediates Azole Resistance in Clinical Isolates and Petite Mutants.. Antimicrob. Agents Chemother. 50: 1384-1392 [Abstract] [Full Text]  
  • Helmerhorst, E. J., Venuleo, C., Sanglard, D., Oppenheim, F. G. (2006). Roles of Cellular Respiration, CgCDR1, and CgCDR2 in Candida glabrata Resistance to Histatin 5. Antimicrob. Agents Chemother. 50: 1100-1103 [Abstract] [Full Text]  
  • Magill, S. S., Shields, C., Sears, C. L., Choti, M., Merz, W. G. (2006). Triazole Cross-Resistance among Candida spp.: Case Report, Occurrence among Bloodstream Isolates, and Implications for Antifungal Therapy. J. Clin. Microbiol. 44: 529-535 [Abstract] [Full Text]  
  • Richard, G.-F., Dujon, B. (2006). Molecular Evolution of Minisatellites in Hemiascomycetous Yeasts. Mol Biol Evol 23: 189-202 [Abstract] [Full Text]  
  • Olson, J. A., Adler-Moore, J. P., Smith, P. J., Proffitt, R. T. (2005). Treatment of Candida glabrata Infection in Immunosuppressed Mice by Using a Combination of Liposomal Amphotericin B with Caspofungin or Micafungin. Antimicrob. Agents Chemother. 49: 4895-4902 [Abstract] [Full Text]  
  • Pina-Vaz, C., Rodrigues, A. G., Costa-de-Oliveira, S., Ricardo, E., Mardh, P.-A. (2005). Potent synergic effect between ibuprofen and azoles on Candida resulting from blockade of efflux pumps as determined by FUN-1 staining and flow cytometry. J Antimicrob Chemother 56: 678-685 [Abstract] [Full Text]  
  • Richard, G.-F., Kerrest, A., Lafontaine, I., Dujon, B. (2005). Comparative Genomics of Hemiascomycete Yeasts: Genes Involved in DNA Replication, Repair, and Recombination. Mol Biol Evol 22: 1011-1023 [Abstract] [Full Text]  
  • Sanguinetti, M., Posteraro, B., Fiori, B., Ranno, S., Torelli, R., Fadda, G. (2005). Mechanisms of Azole Resistance in Clinical Isolates of Candida glabrata Collected during a Hospital Survey of Antifungal Resistance. Antimicrob. Agents Chemother. 49: 668-679 [Abstract] [Full Text]  
  • Borst, A., Raimer, M. T., Warnock, D. W., Morrison, C. J., Arthington-Skaggs, B. A. (2005). Rapid Acquisition of Stable Azole Resistance by Candida glabrata Isolates Obtained before the Clinical Introduction of Fluconazole. Antimicrob. Agents Chemother. 49: 783-787 [Abstract] [Full Text]  
  • Vermitsky, J.-P., Edlind, T. D. (2004). Azole Resistance in Candida glabrata: Coordinate Upregulation of Multidrug Transporters and Evidence for a Pdr1-Like Transcription Factor. Antimicrob. Agents Chemother. 48: 3773-3781 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J. (2004). Rare and Emerging Opportunistic Fungal Pathogens: Concern for Resistance beyond Candida albicans and Aspergillus fumigatus. J. Clin. Microbiol. 42: 4419-4431 [Full Text]  
  • (2004). Fluconazole-Resistant Candida glabrata Pumps the Drug Out. JWatch Infect. Diseases 2004: 7-7 [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»