Epidemiology, practice patterns, and prognostic factors for candidemia; and characteristics of fourteen patients with breakthrough Candida bloodstream infections: a single tertiary hospital experience in Japan

Ryuichi Hirano,1,2 Yuichi Sakamoto,3 Junichi Kitazawa,3 Shoji Yamamoto,1 Hiroyuki Kayaba2 1Department of Pharmacy, Aomori Prefectural Central Hospital, Aomori, Japan; 2Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 3Department of Laboratory Medicine, Aomori Prefectural Central Hospital, Aomori, Japan Background: Candidemia is associated with high mortality, and its prognostic factors need to be examined in more detail in order to improve its management. A case of breakthrough (BT) candidemia is defined as the development of candidemia during antifungal therapy. The microbiological characteristics of and appropriate clinical practices for BT candidemia remain unclear. Objectives: The primary objective of the present study was to identify the prognostic factors of candidemia, while the secondary objective was to elucidate the microbiological characteristics of patients with BT candidemia. Materials and methods: A total of 121 patients diagnosed with candidemia between January 2007 and December 2016 were enrolled in this study. The primary outcome was the 30-day mortality rate. Results: The overall incidence of candidemia was 0.056 cases/1000 inpatients. Among the 126 Candida isolated, C. albicans accounted for 36%, C. parapsilosis 26%, C. glabrata 12%, C. ­guilliermondii 14%, C. tropicalis 3%, C. pelliculos 1%, and other unidentifiable Candida ­species 8%. The 30-day mortality rate was 33%. In a multivariate Cox hazard analysis, C. albicans, the absence of antifungal therapy, age, lung disease, and mechanical ventilation were associated with a high mortality rate, whereas C. parapsilosis, the removal of a central venous catheter, and surgical wards were associated with a lower mortality rate. Fourteen patients had BT candidemia. A significant difference was observed in the proportion of C. guilliermondii and other Candida species exhibiting resistance to fluconazole and voriconazole, between patients with and without BT candidemia. Resistance to fluconazole was prominent in patients that developed candidemia with a history of azole antifungal agents. Conclusion: The prompt initiation of antifungal therapy and removal of central venous ­catheter were essential for better outcomes. A class switch to other antifungal agents needs to be considered in empirical antifungal therapy for BT candidemia with a history of exposure to azole antifungal agents. Keywords: antifungal stewardship, breakthrough candidemia, candidemia, Japa