This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Redding, S. W. Articles by Lopez-Ribot, J. Search for Related Content PubMed PubMed Citation Articles by Redding, S. W. Articles by Lopez-Ribot, J.

Multiple Patterns of Resistance to Fluconazole in Candida glabrata Isolates from a Patient with Oropharyngeal Candidiasis Receiving Head and Neck Radiation

Department of General Dentistry,¹ Department of Medicine, Division of Infectious Diseases,² Department of Pathology,³ Department of Radiation Oncology, The University of Texas Health Science Center and The South Texas Veterans Healthcare System, San Antonio, Texas 78229-3900⁴

Received 12 August 2002/ Returned for modification 18 September 2002/ Accepted 8 November 2002

Candida glabrata has emerged in recent years as a significant cause of systemic fungal infection. We have previously reported on the first three patients receiving radiation for head and neck cancer to develop oropharyngeal candidiasis due to C. glabrata. The goal of this study was to track the development of increased fluconazole resistance in C. glabrata isolates and to evaluate previously described genetic mechanisms associated with this resistance from one of these three patients. The patient was a 52-year-old man with squamous cell carcinoma treated with radiation. At week 7 of his radiation, he developed oropharyngeal candidiasis, which was treated with 200 mg of fluconazole daily for 2 weeks. Serial cultures from this and three subsequent time points yielded C. glabrata. Isolates from these cultures were subjected to antifungal susceptibility testing, DNA karyotyping, and evaluation of the expression of genes previously associated with C. glabrata resistance to fluconazole, CgCDR1, CgCDR2, and CgERG11. Two strains (A and B) of C. glabrata were identified and found to display different patterns of resistance development and gene expression. Strain A developed resistance over a 2-week period and showed no overexpression of these genes. In contrast, strain B first showed resistance 6 weeks after fluconazole therapy was discontinued but showed overexpression of all three genes. In conclusion, development of resistance to fluconazole by C. glabrata is a highly varied process involving multiple molecular mechanisms.

This article has been cited by other articles:

• Vermitsky, J.-P., Self, M. J., Chadwick, S. G., Trama, J. P., Adelson, M. E., Mordechai, E., Gygax, S. E. (2008). Survey of Vaginal-Flora Candida Species Isolates from Women of Different Age Groups by Use of Species-Specific PCR Detection. J. Clin. Microbiol. 46: 1501-1503 [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]  
• Pfaller, M. A., Diekema, D. J. (2007). Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem. Clin. Microbiol. Rev. 20: 133-163 [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]  
• Uko, S., Soghier, L. M., Vega, M., Marsh, J., Reinersman, G. T., Herring, L., Dave, V. A., Nafday, S., Brion, L. P. (2006). Targeted Short-Term Fluconazole Prophylaxis Among Very Low Birth Weight and Extremely Low Birth Weight Infants. Pediatrics 117: 1243-1252 [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]  
• 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]  
• Barchiesi, F., Spreghini, E., Maracci, M., Fothergill, A. W., Baldassarri, I., Rinaldi, M. G., Scalise, G. (2004). In Vitro Activities of Voriconazole in Combination with Three Other Antifungal Agents against Candida glabrata. Antimicrob. Agents Chemother. 48: 3317-3322 [Abstract] [Full Text]  
• Barker, K. S., Crisp, S., Wiederhold, N., Lewis, R. E., Bareither, B., Eckstein, J., Barbuch, R., Bard, M., Rogers, P. D. (2004). Genome-wide expression profiling reveals genes associated with amphotericin B and fluconazole resistance in experimentally induced antifungal resistant isolates of Candida albicans. J Antimicrob Chemother 54: 376-385 [Abstract] [Full Text]  
• Pfaller, M. A., Messer, S. A., Boyken, L., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2004). Geographic Variation in the Susceptibilities of Invasive Isolates of Candida glabrata to Seven Systemically Active Antifungal Agents: a Global Assessment from the ARTEMIS Antifungal Surveillance Program Conducted in 2001 and 2002. J. Clin. Microbiol. 42: 3142-3146 [Abstract] [Full Text]  
• Brun, S., Berges, T., Poupard, P., Vauzelle-Moreau, C., Renier, G., Chabasse, D., Bouchara, J.-P. (2004). Mechanisms of Azole Resistance in Petite Mutants of Candida glabrata. Antimicrob. Agents Chemother. 48: 1788-1796 [Abstract] [Full Text]