Drug-Resistant Candida glabrata Infection in Cancer Patients - Volume 20, Number 11—November 2014 - Emerging Infectious Disease journal - CDC

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Drug-Resistant Candida glabrata Infection in Cancer Patients - Volume 20, Number 11—November 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 11—November 2014

Research

Drug-Resistant Candida glabrata Infection in Cancer Patients

On This Page

• Patients and Methods
• Results
• Discussion
• Suggested Citation

Figures

• Figure

Tables

• Table 1
• Table 2
• Table 3

Technical Appendicies

• Technical Appendix

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Dimitrios Farmakiotis1, Jeffrey J. Tarrand, and Dimitrios P. Kontoyiannis 

Author affiliations: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA (D. Farmakiotis, J.J. Tarrand, D.P. Kontoyiannis); Baylor College of Medicine, Houston (D. Farmakiotis)

Suggested citation for this article

Abstract

Cancer patients are at risk for candidemia, and increasing Candida spp. resistance poses an emerging threat. We determined rates of antifungal drug resistance, identified factors associated with resistance, and investigated the correlation between resistance and all-cause mortality rates among cancer patients with ≥1 C. glabrata–positive blood culture at MD Anderson Cancer Center, Houston, Texas, USA, during March 2005–September 2013. Of 146 isolates, 30 (20.5%) were resistant to fluconazole, 15 (10.3%) to caspofungin, and 10 (6.8%) to multiple drugs (9 caspofungin-resistant isolates were also resistant to fluconazole, 1 to amphotericin B). Independently associated with fluconazole resistance were azole preexposure, hematologic malignancy, and mechanical ventilation. Independently associated with caspofungin resistance were echinocandin preexposure, monocytopenia, and total parenteral nutrition. Fluconazole resistance was highly associated with caspofungin resistance, independent of prior azole or echinocandin use. Caspofungin resistance was associated with increased 28-day all-cause mortality rates. These findings highlight the need for good stewardship of antifungal drugs.

Patients with cancer are often at risk for candidemia because of indwelling catheters, abdominal surgery, use of cytotoxic chemotherapy, parenteral nutrition, antibacterial drugs, and corticosteroids (1–5). Increasing drug resistance among Candida spp. poses an emerging threat to these patients. Moreover, the widespread prophylactic use of azoles in patients with hematologic malignancies and a reduced threshold for empiric initiation of antifungal treatment among critically ill patients have led to a notable shift from infections with C.albicans to infections with non-albicans Candida species (2–4). Among cancer patients, one of the most commonCandida species isolated is C. glabrata (3–5), which is the main species exhibiting multiazole, echinocandin, and multidrug resistance (resistance to at least 2 classes of antifungal drugs) (6–9).

Recently, on the basis of the integration of epidemiologic, molecular, and limited clinical data, the Clinical Laboratory Standards Institute (CLSI) updated antifungal susceptibility break points for Candida spp. (10,11). According to the new definitions, rates of caspofungin nonsusceptibility among C. glabrata clinical isolates range from <10% (12) to as high as 62% (13). Previous use of azoles or echinocandins are strong predictors of resistance to the respective classes (3,5,6,14,15), but little is known about the current rates of cross-resistance between azoles and echinocandins in patients with cancer or about additional clinical factors that could be associated with resistance. In a contemporary cohort of cancer patients with C. glabrata fungemia, we determined rates of in vitro resistance and cross-resistance to azoles and echinocandins, identified factors associated with resistance, and investigated the association between antifungal resistance and all-cause mortality rates.

Dr Farmakiotis is board certified in internal medicine and works as a transplant infectious diseases fellow at Brigham and Women’s Hospital and Dana Farber Cancer Institute. His research interests focus on fungal infections in immunocompromised patients with cancer, particularly those with hematologic malignancies.

Acknowledgments

We thank Dong Sik Yung for his contribution to data collection, Nathaniel D. Albert for technical support, and Ying Jang for her assistance with statistical analyses.

D.P.K. is the Frances King Black Endowed Professor for Cancer Research and. has received research support and honoraria from Astellas US, Pfizer, Gilead, and Merck & Co., Inc.

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Figure

• Figure. A) Mean 28-day survival (days, mean ± SE) and B) Kaplan-Meier survival curves, relative to caspofungin MIC and susceptibility in Candida glabrata isolates, according to the updated definitions (susceptible: MIC<0.25...

Tables

• Table 1. Basic demographic, clinical, and laboratory characteristics for 144 cancer patients with 146 episodes of Candida glabrata fungemia, MD Anderson Cancer Center, Houston, Texas, USA, March 2005–September 2013
• Table 2. Factors present at the time of candidemia and associated with fluconazole resistance, in cancer patients with Candida glabrata fungemia, MD Anderson Cancer Center, Houston, Texas, USA, March 2005–September 2013
• Table 3. Factors present at the time of candidemia and associated with caspofungin resistance in cancer patients with Candida glabrata fungemia, MD Anderson Cancer Center, Houston, Texas, USA, March 2005–September 2013

Technical Appendix

• Technical Appendix.  123 KB

Suggested citation for this article: Farmakiotis D, Tarrand JJ, Kontoyiannis DP. Drug-resistant Candida glabrata infection in cancer patients. Emerg Infect Dis [Internet]. 2014 Nov [date cited]. http://dx.doi.org/10.3201/eid2011.140685

DOI: 10.3201/eid2011.140685

1Current affiliation: Harvard Medical School Brigham and Women’s Hospital and Dana Farber Cancer Institute, Boston, Massachusetts, USA