Clinical characteristics of the first cases of invasive candidiasis in China due to pan-echinocandin-resistant Candida tropicalis and Candida glabrata isolates with delineation of their resistance mechanisms

Abstract: Echinocandin antifungal agents have become the first-line therapy for invasive candidiasis (IC) in many countries. Despite their increasing use, resistance to this class of drug is, overall, still uncommon. Here, we report two patients from the People’s Republic of China with IC, one with infection caused by pan-echinocandin-resistant Candida tropicalis and the other by pan-echinocandin-resistant Candida glabrata . We also describe the mechanisms of drug resistance of these isolates. The echinocandin-resistant C. glabrata isolate was cultured from ascitic fluid of a 46-year-old male patient with intra-abdominal IC developing after surgery in 2012. This patient had had no prior antifungal exposure. The echinocandin-resistant C. tropicalis isolate was cultured from chest drainage fluid of a 60-year-old female patient with severe coronary disease and lung infection. Prior to culture and identification of the isolate, the patient had received micafungin treatment for 19 days. Both isolates were cross-resistant to micafungin, anidulafungin, and caspofungin, with minimum inhibitory concentration values of ≥2 µg/mL. The amino acid substitution E655K was found adjacent to the FKS2 HS1 region of the C. glabrata isolate, while the substitution S80P were found in the FKS1 HS1 region of the C. tropicalis isolate. This report highlights the emergence of echinocandin resistance in two important non- albicans Candida species. Although the overall prevalence of echinocandin resistance is low in the People’s Republic of China, monitoring of antifungal susceptibility trends in all Candida species is warranted. Keywords: Candida tropicalis , Candida glabrata , echinocandins, antifungal resistance, People’s Republic of China