The changing spectrum of Saccharomycotina yeasts causing candidemia: phylogeny mirrors antifungal susceptibility patterns for azole drugs and amphothericin B

Abstract

Ascomycetous yeast species belonging to the subphylum Saccharomycotina (Ascomycota, Fungi) may cause a variety of pathologies in humans. Candida albicans accounts for almost half of candidemia cases but the emergence of uncommon yeasts in the clinical setting is increasing. Here, we highlight the epidemiology of Saccharomycotina budding yeasts causing bloodstream infections, address antifungal susceptibility patterns and unravel how the latter corresponds to their phylogenetic relationship. Only studies applying Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and/or sequence-based identification methods were considered. A ribosomal DNA-based phylogeny was used to present phylogenetic relationships of yeasts pathogens and their close relatives and to show how the antifungal susceptibility patterns for amphotericin B and azole drugs correlate with the clades found. Candida albicans was still the leading cause of yeast-related sepsis, but 22 other Saccharomycotina yeast species were also identified as a common cause of sepsis based on the literature. Similar minimum inhibitory concentration (MIC) values are found between phylogenetically closely related species and appear to be clade-specific to a large extent. This demonstrates that phylogeny may serve as a first guidance for treatment of emerging yeasts with uncommon susceptibility patterns due to intrinsic resistance.

Epidemiological features of nosocomial candidaemia in neonates, infants and children: A multicentre study in Iran

“…Surprisingly, we isolated emerging Candida species, namely C. dubliniensis , C. fabianii , C. utilis , C. eremophila and C. melibiosica , from infected paediatric patients, which have also been previously isolated in other countries. In agreement with other studies, the majority of these emerging Candida species showed reduced susceptibility to antifungal agents . Uncommon Candida species often go undetected in routine microbiology laboratories, and the clinical significance of these species remains underestimated.…”

“…Interestingly, all tested antifungals showed potent antifungal activity against other isolates from the C. parapsilosis complex. The low frequency of C. glabrata and C. krusei detected in the current study is consistent with the observations of Charsizadeh et al This can be explained by (a) the representation of a paediatric population in the current study, as C. glabrata is responsible for 4.5% of cases in paediatric patients compared with 12.4% of cases among adult patients; and (b) the low rate of administration of azole prophylaxis …”

“…In agreement with other studies, the majority of these emerging Candida species showed reduced susceptibility to antifungal agents. 22,[30][31][32][33] Uncommon Candida species often go undetected in routine microbiology laboratories, and the clinical significance of these species remains underestimated. In developing countries, considering the lack of adequate facilities in hospital laboratories, identification of Candida species is limited to conventional methods.…”

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

“…The taxonomic classification and naming of Saccharomycotina yeasts is currently being revisited and will ultimately entered into the clinics. The fact that opportunistic Candida pathogens belong to such diverged clades indicates that their ability to infect human has emerged independently multiple times during evolution, which is further highlighted by the variable molecular mechanisms of virulence and differential antifungal susceptibility patterns [18,21,22].…”

“…An important consideration regarding the issue of susceptibility to antifungal drugs of different pathogens is that resistance can have different origins. On the one hand, different species have different intrinsic susceptibility to different antifungal drugs [21,22], which defines a shared trait of a species, but is more or less variable among strains. Here again, different species might have different potentials to adapt to different drugs, and hence, the acquired resistance is not entirely independent of the phylogenetic background.…”