Comparison of fungemia caused by Candida and non-Candida rare yeasts: a retrospective study from a tertiary care hospital.

Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited, and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor, and outcome. In addition, a candidemia group, including patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to the reference method. A total of 85 patients with fungemia episodes were included: 25 with NCY fungemia and 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole, and amphotericin B were ≤ 2 µg/ml, and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs, and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters, and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species was the problem, particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.

Among all fungemia episodes, hematological malignancies, immunosuppressive therapy, neutropenia, and preexposure to antifungals were risk factors for non-Candida yeast fungemia; diabetes mellitus, urinary catheters, and total parenteral nutrition were risks for candidemia.

Candida haemulonii Species Complex: A Mini-review.

Candida haemulonii species complex (CHSC) are emerging multidrug-resistant yeast pathogens able to cause life-threatening human infections in at-risk populations for invasive candidiasis worldwide. A recent laboratory survey conducted in 12 medical centers found that prevalence rates of Candida haemulonii complex isolates rose from 0.9 to 1.7% along the period between 2008 and 2019. We present a mini-review addressing recent aspects of the epidemiology, diagnosis and therapy of infections due to CHSC.

Clinical, Microbiological, and Molecular Characterization of Candia (Starmera) stellimalicola, a Rare Fungal Pathogen Causing Human Infections.

Candia (Starmera) stellimalicola is a yeast species spread worldwide and recovered from varieties of ecological reservoirs, but human infections are rarely reported. In this study, we reported an intra-abdominal infection case caused by C. stellimalicola and described its microbiological and molecular characteristics. C. stellimalicola strains were isolated from ascites fluid of an 82-year-old male patient having diffuse peritonitis with fever and elevated WBC counts. Routine biochemical and MALDI-TOF MS methods failed to identify the pathogenic strains. Phylogenetic analysis of 18S, 26S and internal transcribed space (ITS) rDNA regions, as well as whole-genome sequence identified the strains as C. stellimalicola. Compared with other Starmera species, C. stellimalicola had unique physiological characteristics including thermal tolerance (able to grow at 42 °C), which may prompt its environmental adaptability and potential for opportunistic human infection. Fluconazole minimum inhibitory concentration (MIC) values of the strains identified in this case was 2 mg/L, and the patient had a favorable outcome after receiving fluconazole treatment. In comparison, the majority of C. stellimalicola strains previously documented had high MIC values (≥ 16 mg/L) to fluconazole. In conclusion, with the raise in human infections caused by rare fungal pathogens, molecular diagnostic remains the most efficient way for accurate species identification; and antifungal susceptibility testing is essential to guide proper patient management.

Echinocandins Susceptibility Patterns of 2,787 Yeast Isolates: Importance of the Thresholds for the Detection of FKS Mutations.

Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.

Fungaemia due to rare yeasts in paediatric intensive care units: A prospective study.

BACKGROUND: Considering the emergence of fungaemia due to rare yeasts at our centre, we performed a systematic epidemiologic study on fungaemia due to rare yeast. OBJECTIVES: We undertook the present prospective observational study to explore the epidemiological features and clinical characteristics of fungaemia due to rare yeasts in paediatric ICUs at our centre. METHODS: The successive yeasts isolated from blood at our PICUs during December 2017 through March 2019 were identified by molecular methods. Fungaemia due to yeasts other than C. albicans, C. tropicalis, C. glabrata, C. krusei and C. parapsilosis was categorised as rare yeasts. Antifungal susceptibility testing of the yeast isolates was performed as per clinical and laboratory standards institute (CLSI) guidelines. We also compared different clinical parameters of fungaemia due to common versus rare yeasts, and rare yeasts in neonates versus non-neonates. RESULTS: During the study period, 212 yeast isolates were obtained from 159 patients at PICUs of our hospital, and 127 isolates from 98 patients (61.6%) were categorised as rare yeasts. Neonates acquired fungaemia significantly earlier after ICU admission than non-neonates (median:4 vs 6 days; p = .005). Regarding epidemiology study of rare yeast fungaemia, Wickerhamomyces anomalus (43.8%) and Candida utilis (40.8%) were common isolates; surgical intervention and gastrointestinal disease were significantly associated; overall, azole, echinocandin and amphotericin B resistance was at 9.1%, 1.02% and 1.02%, respectively; overall mortality was 65.3%. CONCLUSIONS: The emergence of rare yeasts especially W. anomalus and C. utilis causing fungaemia in our children demands urgent attention to control the spread.

Fungaemia due to rare yeasts in a tertiary care university centre within 18 years.

BACKGROUND: Fungaemia due to rare yeasts has been recognised as an emerging, clinically relevant, but less investigated condition. Intrinsic resistance or reduced susceptibility of these species to echinocandins or fluconazole remains as a challenge in empirical treatment. OBJECTIVES: To describe the clinical characteristics, administered antifungal agents, outcomes of patients with rare yeasts other than Candida (RY-OTC) fungaemia and determine the antifungal susceptibility profiles of the isolates. PATIENTS AND METHODS: RY-OTC fungaemia between January-2001 and December-2018 were retrospectively evaluated. Antifungal susceptibility tests were performed according to CLSI M27-A3. RESULTS: We identified 19 patients with fungaemia due to 20 RY-OTC (8 Trichosporon asahii, 4 Cryptococcus neoformans, 4 Saprochaete capitata, 3 Rhodotorula mucilaginosa, 1 Trichosporon mucoides) with an incidence of 2.2% among 859 fungaemia episodes. Haematological malignancy was the most common (42%) underlying disorder. In 6 patients, RY-OTC fungaemia developed as breakthrough infection while receiving echinocandins, amphotericin B or fluconazole. Amphotericin B, fluconazole or voriconazole were the drugs of choice for the initial treatment of breakthrough fungaemia. Among patients without previous exposure to antifungals, the most common empirical treatment was an echinocandin (50%), followed by fluconazole (42%) and amphotericin B (8%). Overall mortality was 47%. Worse outcome was most common among patients receiving echinocandins (83% vs 25%, P < .05). Voriconazole and posaconazole showed the highest in vitro activity against all the isolates tested. Amphotericin B MICs were relatively higher and the degree of activity of fluconazole and itraconazole was variable. CONCLUSIONS: Early recognition of RY-OTC and knowledge about their susceptibility patterns remain crucial in initial treatment pending susceptibility data of isolates.

Fluconazole Resistance in Isolates of Uncommon Pathogenic Yeast Species from the United Kingdom.

The triazole drug fluconazole remains one of the most commonly prescribed antifungal drugs, both for prophylaxis in high-risk patients and also as a second-line treatment option for invasive Candida infections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole with Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, which account for the majority of infections due to pathogenic yeast species. However, less common species for which only limited susceptibility data are available are increasingly reported in high-risk patients and from breakthrough infections. The UK National Mycology Reference Laboratory performs routine antifungal susceptibility testing of clinical isolates of pathogenic yeast submitted from across the United Kingdom. Between 2002 and 2016, ∼32,000 isolates were referred, encompassing 94 different yeast species. Here, we present fluconazole antifungal susceptibility data generated using a CLSI methodology over this 15-year period for 82 species (2,004 isolates) of less common yeast and yeast-like fungi, and amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and anidulafungin, with members of the Nakaseomyces clade (C. glabrata, Candida nivariensis, and Candida bracarensis). At least 22 different teleomorph genera, comprising 45 species, exhibited high MICs when tested with fluconazole (>20% of isolates with MICs higher than the clinical breakpoint [≥8 mg/liter] proposed for C. albicans). Since several of these species have been reported anecdotally from breakthrough infections and therapeutic failures in patients receiving fluconazole, the current study underscores the importance of rapid and accurate yeast identification and may aid clinicians dealing with infections with rarer yeasts to decide whether fluconazole would be appropriate.

Clinico-mycological characteristics and outcomes of rare yeast infections.

Unusual fungi, encountered infrequently in practice, present a significant diagnostic challenge, leading to potential delays in diagnosis and treatment. This study aims to describe a number of cases, where infections were caused by rare yeast pathogens. Organisms isolated included rare Candida species, Geotrichum, Lodderomyces and Trichosporon species. The mean duration of the outcome of the patients from microbiological diagnosis was 20 days. A total of 3 patients succumbed to their illness. This study aims to shed light on the varied clinical presentation and outcome of infections caused by rare yeast pathogens.

Saprochaete/Magnusiomyces: identification, virulence factors, and antifungal susceptibility of a challenging rare yeast.

Saprochaete/Magnusiomyces is among rare yeasts which might emerge as causes of breakthrough infections and nosocomial outbreaks. Identification to the species level might be a challenge in clinical laboratories. Data on virulence factors are scarce and antifungal susceptibility testing methodology is not definite. The aim of this study was to confirm species identification of clinical Saprochaete/Magnusiomyces isolates, find out their virulence factors, and obtain antifungal minimum inhibitory concentrations with two reference methods. Of the 57 isolates included, 54 were Saprochaete capitata and four were Saprochaete clavata as identified by ID32C, MALDI-TOF MS, and sequencing. When tested using phenotypic methods, all isolates were negative for coagulase, hemolysis, acid proteinase, and phospholipase, 56.1% were positive for esterase, and 19.3% had intermediate surface hydrophobicity. All isolates formed biofilms, with 40.4% of the isolates producing more biomass than biofilm-positive reference strain Candida albicans MYA-274. Antifungal susceptibility testing needed an adjusted spectrophotometric inoculum than recommended in reference methods for Candida/Cryptococcus. In conclusion, Saprochaete/Magnusiomyces species could be identified using methods available in the clinical laboratories. Despite the disadvantages of the phenotypic methods, esterase positivity was observed for the first time. A high biomass production was observed in biofilms. The need for standardization of antifungal susceptibility testing was brought to attention.

Unlocking the plant growth-promoting potential of yeast spp.: exploring species from the Moroccan extremophilic environment for enhanced plant growth and sustainable farming.

In this study, we successfully isolated two distinct yeasts from Moroccan extreme environments. These yeasts were subjected to molecular characterization by analyzing their Internal Transcribed spacer (ITS) regions. Our research thoroughly characterizes plant growth-promoting abilities and their drought and salt stress tolerance. In a greenhouse assay, we examined the impact of selected yeasts on Medicago sativa's growth. Four treatments were employed: (i) control without inoculation (NI), (ii) inoculation with L1, (iii) inoculation with L2, and (iv) inoculation with the mixture L1 + L2. L1 isolated from Toubkal Mountain shared 99.83% sequence similarity to Rhodotorula mucilaginosa. Meanwhile, L2, thriving in the arid Merzouga desert, displayed a similar identity to Naganishia albida (99.84%). Yeast strains were tolerant to NaCl (2 M) and 60% PEG (polyethylene glycol P6000) in case of drought. Both strains could solubilize phsphorus, with L2 additionally demonstrating potassium solubilization. In addition, both strains produce indole acetic acid (up to 135 µl ml-1), have siderophore ability, and produce aminocyclopropane-1-carboxylic acid deaminase. Isolates L1 and L2, and their consortium showed that the single or combined strain inoculation of M. sativa improved plant growth, development, and nutrient assimilation. These findings pave the way for harnessing yeast-based solutions in agricultural practices, contributing to enhanced crop productivity and environmental sustainability.

Four uncommon clinical fungi, Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii and Wickerhamomyces anomalus, isolated in superficial samples from Côte d'Ivoire.

AIMS: The rare yeast species Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus are increasingly implicated in severe mycoses in immunocompromised patients. This study aimed to assess the prevalence of uncommon yeast species in Côte d'Ivoire. METHODS: The yeast isolates from superficial samples, mainly vaginal swabs, were collected at the Pasteur Institute of Abidjan in a study on the molecular epidemiology of clinical yeast species. Identification relied on MALDI-TOF MS and ITS sequence analysis. Antifungal susceptibility testing was performed using the CLSI method. RESULTS: Of the 315 strains analysed from 227 outpatients, 14 belonged to 4 uncommon species: Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus. None exhibited elevated fluconazole, amphotericin B, caspofungin, ketoconazole, or flucytosin MIC. CONCLUSIONS: The presence of these rare yeasts represents a risk in immunocompromised people. Their adequate and timely identification is a priority. Overall, enhancing the mycoses diagnostic capacities in Côte d'Ivoire, and more generally in African clinical laboratories with limited resources is a critical aim.

A Pragmatic Approach to Susceptibility Classification of Yeasts without EUCAST Clinical Breakpoints.

EUCAST has established clinical breakpoints for the six most common Candida species and Cryptococcus neoformans but not for less common yeasts because sufficient evidence is lacking. Consequently, the question "How to interpret the MIC?" for other yeasts often arises. We propose a pragmatic classification for amphotericin B, anidulafungin, fluconazole, and voriconazole MICs against 30 different rare yeasts. This classification takes advantage of MIC data for more than 4000 isolates generated in the EUCAST Development Laboratory for Fungi validated by alignment to published EUCAST MIC data. The classification relies on the following two important assumptions: first, that when isolates are genetically related, pathogenicity and intrinsic susceptibility patterns may be similar; and second, that even if species are not phylogenetically related, the rare yeasts will likely respond to therapy, provided the MIC is comparable to that against wild-type isolates of more prevalent susceptible species because rare yeasts are most likely "rare" due to a lower pathogenicity. In addition, the treatment recommendations available in the current guidelines based on the in vivo efficacy data and clinical experience are taken into consideration. Needless to say, it is of utmost importance (a) to ascertain that the species identification is correct (using MALDI-TOF or sequencing), and (b) to re-test the isolate once or twice to confirm that the MIC is representative for the isolate (because of the inherent variability in MIC determinations). We hope this pragmatic guidance is helpful until evidence-based EUCAST breakpoints can be formally established.

Infections due to Rare Cryptococcus Species. A Literature Review.

Infections due to rare Cryptococcus species (other than C. neoformans species complex, C. gattii species complex, C. albidus or C. laurentii) are barely reported. The aim of this work is to present a comprehensive literature review of all the papers describing infections due to these species referenced in the main databases (PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar). Clinical and epidemiological data together with laboratory findings (identification and antifungal susceptibility) of each isolate were analyzed. Fifty-eight cryptococosis due to rare species were described in 46 papers between 1934-2018. These reports included 16 rare Cryptococcus spp. that were generally associated with nervous system infections and fungemias. Some species are non-capsulated and are not able to grow at 37 °C. Few species were identified by commercially available methods, making internal transcriber spacer (ITS) and D1/D2 regions sequencing mandatory. The most potent antifungal was amphotericin B (although some species showed high MIC values). The studied strains showed high MICs values to 5-fluorocytosine (all >64 µg/mL), echinocandins (all >8 µg/mL), and fluconazole (>80% of the MICs >4 µg/mL). Due to the scarcity of the data and the absence of guidelines for the treatment of these infections, this review could be informative and could help in the diagnosis and treatment of these infections.

Isavuconazole MIC distribution of 29 yeast species responsible for invasive infections (2015-2017).

OBJECTIVES: Isavuconazole is a recent extended-spectrum triazole with activity against yeasts. However, few data are available about the in vitro activity of rare yeast species. We report the MIC distribution of isavuconazole compared with fluconazole for a large collection of common or rare yeasts. METHODS: Isavuconazole and fluconazole MICs were determined using the EUCAST method for 1457 clinical isolates, mainly recovered from invasive infections, belonging to 29 species. They were sent to the National Reference Centre for Invasive Mycoses & Antifungals between January 2015 and October 2017 and species identification was performed using a polyphasic approach (matrix-assisted laser desorption/ionization time of flight analysis and a molecular method). RESULTS: Isavuconazole had effective in vitro activity against Cryptococcus neoformans (MIC90 < 0.25 mg/L), the five most common Candida spp. (MIC90 ≤ 0.5 mg/L for Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei) and also against the majority of rare species, including Candida kefyr and Candida lusitaniae. A few isolates of C. albicans (0.7%, 3/404), C. glabrata (2.7%, 5/184), C. tropicalis (1.0%, 1/96) and C. parapsilosis (0.8%, 1/127) exhibited MIC ≥4 mg/L. All were also resistant to fluconazole according to the EUCAST breakpoints. Some isolates with isavuconazole MIC ≥4 mg/L were also observed among rarer species: Meyerozyma guilliermondii (8.7%, 2/23), Wickerhamomyces anomalus (10.0%, 1/10). Other rare species Saprochaete clavata, Magnusiomyces capitatus, and Rhodotorula mucilaginosa had high MIC50 (≥1 mg/L) and MIC90 (≥4 mg/L) and could be considered as resistant to isavuconazole. CONCLUSIONS: We confirmed the good in vitro activity of isavuconazole against common Candida, Cryptococcus species and the majority of the rare yeast species studied.