Drug-Resistant Candida glabrata Infection in Cancer Patients

Dimitrios Farmakiotis; Jeffrey J. Tarrand; Dimitrios P. Kontoyiannis

Disclosures

Emerging Infectious Diseases. 2014;20(11):1833-1840. 

In This Article

Abstract and Introduction

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.

Introduction

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 common Candida 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.

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