Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997–2016

Abstract

Background The emergence of antifungal resistance threatens effective treatment of invasive fungal infection (IFI). Invasive candidiasis is the most common health care–associated IFI. We evaluated the activity of fluconazole (FLU) against 20 788 invasive isolates of Candida (37 species) collected from 135 medical centers in 39 countries (1997–2016). The activity of anidulafungin, caspofungin, and micafungin (MCF) was evaluated against 15 308 isolates worldwide (2006–2016). Methods Species identification was accomplished using phenotypic (1997–2001), genotypic, and proteomic methods (2006–2016). All isolates were tested using reference methods and clinical breakpoints published in the Clinical and Laboratory Standards Institute documents. Results A decrease in the isolation of Candida albicans and an increase in the isolation of Candida glabrata and Candida parapsilosis were observed over time. Candida glabrata was the most common non–C. albicans species detected in all geographic regions except for Latin America, where C. parapsilosis and Candida tropicalis were more common. Six Candida auris isolates were detected: 1 each in 2009, 2013, 2014, and 2015 and 2 in 2016; all were from nosocomial bloodstream infections and were FLU-resistant (R). The highest rates of FLU-R isolates were seen in C. glabrata from North America (NA; 10.6%) and in C. tropicalis from the Asia-Pacific region (9.2%). A steady increase in isolation of C. glabrata and resistance to FLU was detected over 20 years in the United States. Echinocandin-R (EC-R) ranged from 3.5% for C. glabrata to 0.1% for C. albicans and C. parapsilosis. Resistance to MCF was highest among C. glabrata (2.8%) and C. tropicalis (1.3%) from NA. Mutations on FKS hot spot (HS) regions were detected among 70 EC-R isolates (51/70 were C. glabrata). Most isolates harboring FKS HS mutations were resistant to 2 or more ECs. Conclusions EC-R and FLU-R remain uncommon among contemporary Candida isolates; however, a slow and steady emergence of resistance to both antifungal classes was observed in C. glabrata and C. tropicalis isolates.

Antifungal drug susceptibility, molecular basis of resistance to echinocandins and molecular epidemiology of fluconazole resistance among clinical Candida glabrata isolates in Kuwait

“…However, resistance to echinocandins in Candida spp. has also appeared in recent years with the highest rate occurring among C. glabrata and breakthrough invasive C. glabrata infections have been reported in patients on micafungin therapy [14][15][16][21][22][23][24] . Resistance to polyenes is also being reported with increasing frequency in clinical C. glabrata isolates [25][26][27][28][29] and a multidrug-resistant phenotype (resistant to azoles and echinocandins) occurring in ICU and non-ICU settings has also been described in recent years 30,31 .…”

SUMOylation in Human Pathogenic Fungi: Role in Physiology and Virulence

“…Candida bloodstream infections (BSIs), a frequent occurrence in immunocompromised individuals, are associated with an average mortality rate of about 40% [47,54,56,75]. The incidence of opportunistic candidemia has increased substantially worldwide in the last two decades, with Candida albicans being the most dominant species followed by the non-albicans species, represented largely by C. glabrata, C. tropicalis and C. parapsilosis, and rapidly emerging C. auris [47,54,75,76]. C. glabrata accounts for 10%-35% of Candida bloodstream infections, based on the geographical distribution [75][76][77][78][79].…”

“…The incidence of opportunistic candidemia has increased substantially worldwide in the last two decades, with Candida albicans being the most dominant species followed by the non-albicans species, represented largely by C. glabrata, C. tropicalis and C. parapsilosis, and rapidly emerging C. auris [47,54,75,76]. C. glabrata accounts for 10%-35% of Candida bloodstream infections, based on the geographical distribution [75][76][77][78][79]. C. albicans is a diploid organism, with key virulence traits of activity of secreted proteases, mating, morphological and colony switching and biofilm formation [80][81][82].…”

Development of Thiazolidinones as Fungal Carbonic Anhydrase Inhibitors

“…increased over the past three decades due to the large use of immunomodulatory agents, extensive use of broad-spectrum antimicrobial drugs, and central vascular catheters [2]. Candida albicans represents the most common cause of invasive candidiasis in the United States of America, followed by C. glabrata, C. parapsilosis, and C. tropicalis [3,4]. Antifungal resistance increased over time also because of the empiric, routine prophylactic, and widespread use of antifungal-based pesticides [5].…”