Emergence of echinocandin-resistant Candida spp. in a hospital setting: a consequence of 10 years of increasing use of antifungal therapy?

Abstract

Since their introduction in the 2000s, echinocandin drugs have become widely used for the treatment and prophylaxis of invasive fungal infections and, notably, invasive candidiasis. Although cases of breakthrough candidiasis in patients receiving echinocandins have been reported, clinical failure during echinocandin treatment due to the acquisition of resistance by a normally susceptible Candida spp. isolate is considered rare. To date, no publications have been published correlating the use of echinocandins and the emergence of echinocandin resistance among Candida species. So, our goal is to report an initial analysis of echinocandin use in relation to the emergence of resistant Candida isolates. We report here a single-centre experience of the emergence of eight resistant isolates belonging to normally susceptible Candida species in six patients receiving echinocandins. We describe the context and analyse the use of echinocandins over the previous decade. For seven of these isolates, we identified FKS gene mutations involved in decreased susceptibility. Seven isolates were obtained in 2011, on the heels of a ten-fold increase in caspofungin use over the preceding decade. In contrast, in 2012, the use of echinocandins decreased in our institution by 19.5 % and, in that year, only one Candida-resistant isolate was detected, despite the stable global epidemiology of invasive candidaemia. This work underlines the necessity of improving the prescription of antifungal drugs. Improvement in the monitoring of strain susceptibility should also be considered in order to better detect the emergence of resistant or non-susceptible yeast strains.

Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

“…However, the reason for the high MIC values for CAS is unclear (45) . Recent works have described a functional point mutation in the glucan synthase (FKS) gene of the C. parapsilosis complex species, which may explain this observation (46) (47) . FKS gene mutations have been shown to be associated with resistance to CAS, as demonstrated by increases in MICs in mutant isolates compared with those of wild-type isolates (48) (49) (50) .…”

CD101: a novel long‐acting echinocandin

“…Overall, current frequency of echinocandin resistance remains relatively low (< 1%) with Candida albicans and most other Candida species except Candida glabrata (Castanheira et al, 2010; Pfaller et al, 2011; Pfaller et al, 2013). However, widespread echinocandin usage has been accompanied by reports of emerging multidrug resistance among clinical Candida isolates (Alexander et al, 2013; Fekkar et al, 2014), as well as epidemiological shifts with increased proportion of less susceptible Candida species (Lortholary et al, 2011). Resistance to echinocandins is associated with mutations in two hot spot (HS) regions in the FKS genes that correlate with clinical failure or poor response to therapy (Perlin, 2011; Shields et al, 2012; Beyda et al, 2014).…”

Multicenter Comparison of the Etest and EUCAST Methods for Antifungal Susceptibility Testing of Candida Isolates to Micafungin

“…Micafungin is now widely used for prophylaxis and treatment of invasive candidiasis (IC) (4,5). During the last decade, acquired resistance of various Candida species to echinocandins has emerged worldwide, including in France, and may become an important issue in the therapeutic management of IC (6)(7)(8)(9)(10).…”