Trends of the Epidemiology of Candidemia in Switzerland: A 15-Year FUNGINOS Survey

Abstract

Background: The increasing incidence of candidemia and emergence of drug-resistant Candida species are major concerns worldwide. Long-term surveillance studies are needed.

Methods: The Fungal Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004-2018), nationwide, epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility, and consumption were stratified in 3 periods (2004-2008, 2009-2013, 2014-2018). Population-based incidence over the period 2009-2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS).

Results: A total of 2273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100 000 inhabitants (P = .022) and 0.86 to 0.99/10 000 patient-days (P = .124), respectively. The proportion of Candida albicans decreased significantly from 60% to 53% (P = .0023), whereas Candida glabrata increased from 18% to 27% (P < .0001). Other non-albicans Candida species remained stable. Candida glabrata bloodstream infections occurred predominantly in the age group 18-40 and above 65 years. A higher proportional increase of C glabrata was recorded in wards (18% to 29%, P < .0001) versus intensive care units (19% to 24%, P = .22). According to Clinical and Laboratory Standards Institute, nonsusceptibility to fluconazole in C albicans was observed in 1% of isolates, and anidulafungin and micafungin nonsusceptibility was observed in 2% of C albicans and C glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (P < .0001).

Conclusions: Over the 15-year period, the incidence of candidemia increased. A species shift toward C glabrata was recently observed, concurring with increased consumption of mold-active triazoles.

Keywords: antifungals; candida; candidemia; epidemiology; resistance.

Figure 1.

(A) Annual incidence of candidemia per 10 000 patient days in the 7 hospitals over the 3 time periods 2004–2008, 2009–2013, and 2014–2018. (B) Species distribution of Candida bloodstream isolates. Total number of Candida isolates per time period are indicated at the top.

Figure 2.

(A) Species distribution of Candida bloodstream isolates according to patients’ age over 2004–2018 (4 hospitals). Total number of Candida isolates per age group are indicated at the top. (B) Species distribution of Candida bloodstream isolates according to patients’ location in the hospital over 2004–2018 (7 hospitals). Total number of Candida isolates per time period and ward are indicated at the top. Other Candida spp included (total numbers): Candida dubliniensis (n = 65), C lusitaniae (n = 20), Candida pelliculosa (n = 13), Candida kefyr (n = 11), Candida guilliermondii (n = 8), C norvegensis (n = 8), Candida africana (n = 5), Candida orthopsilosis (n = 4), Candida nivariensis (n = 4), Candida fabianii (n = 3), Candida inconspicua (n = 2), Candida palmioleophila (n = 2), Candida rugosa (n = 1), Candida pulcherrima (n = 1).

Figure 3.

(A) Annual consumption of broad-spectrum antibiotics and antifungals in Defined Daily Doses (DDDs) per 100 patient days over 2004–2018. (B) Annual consumption of antifungals in DDDs per 100 patient days over 2004–2018. (C) Annual consumption of azoles in DDDs per 100 patient days over 2004–2018. Data of 7 hospitals are reported. Broad-spectrum antibiotics include the following: cefepime, piperacillin/tazobactam, imipenem, and meropenem. Antifungals include fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, amphotericin B deoxycholate, liposomal amphotericin B, caspofungin, and anidulafungin. The DDDs were defined as follows: cefepime 4 grams, piperacillin/tazobactam 14 grams, imipenem 2 grams, meropenem 3 grams; fluconazole 0.4 grams, itraconazole 0.2 grams, voriconazole 0.4 grams, posaconazole 0.3–0.6 grams, isavuconazole 0.2 grams, amphotericin B deoxycholate 0.07 grams, liposomal amphotericin B 0.21 grams, caspofungin 0.05 grams, and anidulafungin 0.2 grams.