Uncommon Candida and Other Opportunistic Yeast-Like Fungi: Diagnosis and Treatment

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Fungal Pathogens".

Deadline for manuscript submissions: closed (5 December 2021) | Viewed by 30767

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Guest Editor
Department of Laboratory Medicine and Pathology, Hamad medical Corporation, Doha, Qatar
Interests: clinical mycology; diagnostic microbiology; aspergillosis; candidemia; mucormycosis; fungal infections; filamentous fungi; infectious diseases
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Special Issue Information

Dear colleagues.

Despite therapeutic advances, invasive infections due to Candida spp. constitute the predominant group of hospital-based fungal infections worldwide. These infections are an important cause of morbidity and mortality in hospitalized patients with serious underlying diseases such as hemato-oncological malignancies—especially immunocompromised patients.

The present trend of Candida infections shows that a large proportion of bloodstream infections are due to Candida species other than C. albicans, particularly among hematological, transplant, and intensive care unit patients. Candidemia caused by other uncommon species is less well known, and data have been reported only in small case series. However, these uncommon fungal species have emerged as a new health threat to hospitalized patients and are endemic in some areas. The widespread use of immunosuppressive therapies, broad-spectrum antibiotics, and antifungal prophylaxis have been associated with a continuous shift from C. albicans to various non-albicans Candida spp. during the past two decades, and may further increase the role of Candida species as the causative pathogens among high-risk patients. C. auris has emerged globally as a multidrug-resistant health-care-associated fungal pathogen. Recent reports highlight ongoing challenges due to the diagnosis and treatment related to high rates of antifungal drug resistance, and significant patient mortality. Other non-albicans Candida species are increasingly being isolated, and the use of antifungal drugs such as azoles for prophylaxis and echinocandins that are being used more frequently among high-risk populations have been associated with a continuous shift from C. albicans to various non-albicans Candida spp. during the past two decades. Moreover, uncommon Candida spp. have emerged as causes of nosocomial bloodstream infections. Those isolates commonly exhibit decreased in vitro susceptibility to antifungal agents.

Invasive infections due to rare yeast-like fungi such as Trichosporon and Geotrichum constitute emerging but poorly investigated conditions. Because most institutions have had limited experience with infections caused by uncommon Candida and other opportunistic yeast-like fungi, we encourage further studies on challenges in the diagnosis, treatment, and prevention of the cases caused by these pathogens.

We look forward to your contribution.

Dr. Saad Taj-Aldeen
Guest Editor

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Keywords

  • yeast-like fungi
  • Trichosporon
  • Geotrichum
  • infectious disease

Published Papers (9 papers)

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Research

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9 pages, 914 KiB  
Article
Serum Cytokine Profile in Patients with Candidemia versus Bacteremia
by Saad J. Taj-Aldeen, Fayaz Ahmad Mir, Siveen K. Sivaraman and Atqah AbdulWahab
Pathogens 2021, 10(10), 1349; https://doi.org/10.3390/pathogens10101349 - 19 Oct 2021
Cited by 1 | Viewed by 1806
Abstract
Bloodstream Candida infections constitute a major threat for hospitalized patients in intensive care units and immunocompromised hosts. Certain serum cytokines play a decisive role in anti-microbial host defense. Cytokines may act as discriminatory biomarkers that can significantly increase in candidemia compared to bacteremia [...] Read more.
Bloodstream Candida infections constitute a major threat for hospitalized patients in intensive care units and immunocompromised hosts. Certain serum cytokines play a decisive role in anti-microbial host defense. Cytokines may act as discriminatory biomarkers that can significantly increase in candidemia compared to bacteremia patients. The concentration of secreted cytokine/chemokines was determined using a multiplexed cytometric bead array run on a cell analyzer. The cytokines tested during the study were interleukin (IL)-1β, IL-6, IL-17A, IL-10, IFN-γ, IL-4, IL-2, IL-8, IL-12p70 and the tumor necrosis factor (TNF)-α. The cytokines of 51 candidemia patients were characterized and compared to the cytokine levels of 20 bacteremia patients. Levels were significantly elevated in patients with bloodstream infections compared to healthy controls. Cytokines comprising IL-2, IL-17A, IL-6 and IL-10 were significantly elevated in the patients with bloodstream Candida infection as compared to the patients having bloodstream bacterial infections. The levels were found to be promising as a potential diagnostic marker for bloodstream Candida infections. Full article
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11 pages, 923 KiB  
Article
Unpredictable In Vitro Killing Activity of Amphotericin B against Four Candida auris Clades
by Zoltán Papp, Andrew M. Borman, Lajos Forgács, Renátó Kovács, Zoltán Tóth, Chiu Chun-Ju, Gábor Kardos, Béla Juhász, Judit Szilvássy and László Majoros
Pathogens 2021, 10(8), 990; https://doi.org/10.3390/pathogens10080990 - 6 Aug 2021
Cited by 6 | Viewed by 2353
Abstract
Candida auris is an emerging multiresistant yeast against which amphotericin B (AMB) is still the first therapeutic choice in certain clinical situations (i.e., meningitis, endophthalmitis, and urinary tract infections). As data about the in vitro killing activity of AMB against C. auris clades [...] Read more.
Candida auris is an emerging multiresistant yeast against which amphotericin B (AMB) is still the first therapeutic choice in certain clinical situations (i.e., meningitis, endophthalmitis, and urinary tract infections). As data about the in vitro killing activity of AMB against C. auris clades are lacking, we determined MICs, minimum fungicidal concentrations (MFCs), and killing activity of AMB against 22 isolates representing the 4 major C. auris clades (South Asian n = 6; East Asian n = 4; South African n = 6, and South American n = 6). MIC values were ≤1 mg/L regardless of clades; MFC ranges were, 1–4 mg/L, 2–4 mg/L, 2 mg/L, and 2–8 mg/L for South Asian, East Asian, South African, and South American clades, respectively. AMB showed concentration-, clade-, and isolate-dependent killing activity. AMB was fungicidal at 1 mg/L against two of six, two of four, three of six, and one of six isolates from the South Asian, East Asian, South African, and South American clades, respectively. Widefield fluorescence microscopy showed cell number decreases at 1 mg/L AMB in cases of the South Asian, East Asian, and South African clades. These data draw attention to the weak killing activity of AMB against C. auris regardless of clades, even when MICs are low (≤1 mg/L). Thus, AMB efficacy is unpredictable in treatment of invasive C. auris infections. Full article
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8 pages, 634 KiB  
Communication
Uncommon Non-Candida Yeasts in Healthy Turkeys—Antimicrobial Susceptibility and Biochemical Characteristic of Trichosporon Isolates
by Kamila Bobrek, Ireneusz Sokół and Andrzej Gaweł
Pathogens 2021, 10(5), 538; https://doi.org/10.3390/pathogens10050538 - 30 Apr 2021
Cited by 1 | Viewed by 1789
Abstract
The microbiota of the gastrointestinal tract of humans and animals is inhabited by a diverse community of bacteria, fungi, protozoa, and viruses. In cases where there is an imbalance in the normal microflora or an immunosuppression on the part of the host, these [...] Read more.
The microbiota of the gastrointestinal tract of humans and animals is inhabited by a diverse community of bacteria, fungi, protozoa, and viruses. In cases where there is an imbalance in the normal microflora or an immunosuppression on the part of the host, these opportunistic microorganisms can cause severe infections. The study presented here evaluates the biochemical and antifungal susceptibility features of Trichosporon spp., uncommon non-Candida strains isolated from the gastrointestinal tract of healthy turkeys. The Trichosporon coremiiforme and Trichosporon (Apiotrichum) montevideense accounted for 7.7% of all fungi isolates. The biochemical tests showed that Trichosporon coremiiforme had active esterase (C4), esterase-lipase (C8) valine arylamidase, naphthol-AS-BI phosphohydrolase, α-galactosidase, and β-glucosidase. Likewise, Trichosporon montevideense demonstrated esterase-lipase (C8), lipase (C14), valine arylamidase, naphthol-AS-BI phosphohydrolase, α-galactosidase, and β-glucosidase activity. T.coremiiforme and T. monteviidense isolated from turkeys were itraconazole resistant and amphotericin B, fluconazole, and voriconazole susceptible. Compared with human isolates, the MIC range and MIC values of turkey isolates to itraconazole were in a higher range limit in both species, while MIC values to amphotericin B, fluconazole, and voriconazole were in a lower range limit. Furthermore, the obtained ITS1—5.8rRNA—ITS2 fragment sequences were identical with T. coremiiforme and T. montevideense sequences isolated from humans indicating that these isolates are shared pathogens. Full article
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9 pages, 1310 KiB  
Communication
Antimicrobial Peptides Pom-1 and Pom-2 from Pomacea poeyana Are Active against Candidaauris, C. parapsilosis and C. albicans Biofilms
by Heinz Fabian Raber, Jetmira Sejfijaj, Ann-Kathrin Kissmann, Andreas Wittgens, Melaine Gonzalez-Garcia, Annia Alba, Antonio A. Vázquez, Fidel E. Morales Vicente, Julio Pérez Erviti, Dennis Kubiczek, Anselmo Otero-González, Armando Rodríguez, Ludger Ständker and Frank Rosenau
Pathogens 2021, 10(4), 496; https://doi.org/10.3390/pathogens10040496 - 20 Apr 2021
Cited by 12 | Viewed by 2451
Abstract
Recently two peptides isolated from the Cuban freshwater snail Pomacea poeyana (Pilsbry, 1927) were described to have antimicrobial activity against bacterial pathogens. Here we show considerable activities of Pom-1 and Pom-2 to reduce the viability of C. albicans, C. parapsilosis and the [...] Read more.
Recently two peptides isolated from the Cuban freshwater snail Pomacea poeyana (Pilsbry, 1927) were described to have antimicrobial activity against bacterial pathogens. Here we show considerable activities of Pom-1 and Pom-2 to reduce the viability of C. albicans, C. parapsilosis and the less common species C. auris measured as the decrease of metabolic activity in the resazurin reduction assay for planktonic cells. Although these activities were low, Pom-1 and Pom-2 turned out to be highly potent inhibitors of biofilm formation for the three Candida species tested. Whereas Pom-1 was slightly more active against C. albicans and C. parapsilosis as representatives of the more common Candida species Pom-2 showed no preference and was fully active also against biofilms of the more uncommon species C. auris. Pom-1 and Pom-2 may represent promising lead structures for the development of a classical peptide optimization strategy with the realistic aim to further increase antibiofilm properties and other pharmacologic parameters and to generate finally the first antifungal drug with a pronounced dedication against Candida biofilms. Full article
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10 pages, 266 KiB  
Article
Predominance of Candida Glabrata among Non-albicans Candida Species in a 16-Year Study of Candidemia at a Tertiary Care Center in Lebanon
by Aline El Zakhem, Rachid Istambouli, Maria Alkozah, Amal Gharamti, Mohamad Ali Tfaily, Jean-Francois Jabbour, George F. Araj, Hani Tamim and Souha S. Kanj
Pathogens 2021, 10(1), 82; https://doi.org/10.3390/pathogens10010082 - 19 Jan 2021
Cited by 14 | Viewed by 2400
Abstract
Background: Candidemia is associated with a high mortality rate, and its incidence is increasing worldwide with a rise in non-albicans candidemia (NAC). Epidemiologic data from Arab countries are scarce and there are no data from Lebanon; Methods: This is a single-center retrospective [...] Read more.
Background: Candidemia is associated with a high mortality rate, and its incidence is increasing worldwide with a rise in non-albicans candidemia (NAC). Epidemiologic data from Arab countries are scarce and there are no data from Lebanon; Methods: This is a single-center retrospective chart review of patients with candidemia in a tertiary care center in Lebanon from 2004 to 2019. We extracted data on patient characteristics, isolated Candida species antifungal susceptibility, management and outcomes; Results: We included 170 cases of candidemia. NAC was more common than albicans candidemia (64.7% vs. 35.3%). C. glabrata was the most common non-albicans species (37 isolates) followed by C. tropicalis (14). Recent use of antifungals was a risk factor for NAC (OR = 2.8, p = 0.01), while the presence of a central venous catheter was protective (OR = 0.41, p = 0.02). Fluconazole resistance was 12.5% in C. albicans and 21.5% in non-albicans spp. Mortality at 30 days was 55.5%, with no difference between NAC and albicans candidemia. It was higher in older and critically ill patients but lower in patients whose central venous catheter was removed after detecting fungemia; Conclusions: Candidemia is associated with high mortality in Lebanon, with a predominance of NAC and high prevalence of C. glabrata. Full article

Review

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45 pages, 1335 KiB  
Review
Overview on the Infections Related to Rare Candida Species
by Sunil Kumar, Awanish Kumar, Maryam Roudbary, Rasoul Mohammadi, Lucia Černáková and Célia Fortuna Rodrigues
Pathogens 2022, 11(9), 963; https://doi.org/10.3390/pathogens11090963 - 24 Aug 2022
Cited by 21 | Viewed by 5657
Abstract
Atypical Candida spp. infections are rising, mostly due to the increasing numbers of immunocompromised patients. The most common Candida spp. is still Candida albicans; however, in the last decades, there has been an increase in non-Candida albicans Candida species infections (e.g., [...] Read more.
Atypical Candida spp. infections are rising, mostly due to the increasing numbers of immunocompromised patients. The most common Candida spp. is still Candida albicans; however, in the last decades, there has been an increase in non-Candida albicans Candida species infections (e.g., Candida glabrata, Candida parapsilosis, and Candida tropicalis). Furthermore, in the last 10 years, the reports on uncommon yeasts, such as Candida lusitaniae, Candida intermedia, or Candida norvegensis, have also worryingly increased. This review summarizes the information, mostly related to the last decade, regarding the infections, diagnosis, treatment, and resistance of these uncommon Candida species. In general, there has been an increase in the number of articles associated with the incidence of these species. Additionally, in several cases, there was a suggestive antifungal resistance, particularly with azoles, which is troublesome for therapeutic success. Full article
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15 pages, 280 KiB  
Review
Invasive Trichosporonosis in Neonates and Pediatric Patients with Malignancies or Hematologic Disorders
by Maria Kourti and Emmanuel Roilides
Pathogens 2022, 11(2), 242; https://doi.org/10.3390/pathogens11020242 - 12 Feb 2022
Cited by 3 | Viewed by 2074
Abstract
(1) Background: Trichosporon species have emerged as important opportunistic fungal pathogens, with Trichosporon asahii being the leading and most frequent cause of invasive disease. (2) Methods: We performed a global review focused on invasive trichosporonosis in neonates and pediatric patients with malignancies or [...] Read more.
(1) Background: Trichosporon species have emerged as important opportunistic fungal pathogens, with Trichosporon asahii being the leading and most frequent cause of invasive disease. (2) Methods: We performed a global review focused on invasive trichosporonosis in neonates and pediatric patients with malignancies or hematologic disorders. We reviewed case reports and case series of trichosporonosis due to T. asahii published since 1994, the year of the revised taxonomic classification. (3) Results: Twenty-four cases of invasive trichosporonosis were identified in neonates with the presence of central venous catheter and use of broad-spectrum antibiotics recognized as the main predisposing factors. Thirty-two cases were identified in children with malignancies or hematologic disorders, predominantly with severe neutropenia. Trichosporon asahii was isolated from blood in 24/32 (75%) pediatric cases. Cutaneous involvement was frequently observed in invasive trichosporonosis. Micafungin was the most commonly used prophylactic agent (9/22; 41%). Ten patients receiving prophylactic echinocandins were identified with breakthrough infections. A favorable outcome was reported in 12/16 (75%) pediatric patients receiving targeted monotherapy with voriconazole or combined with liposomal amphotericin B. Overall mortality in neonates and children with malignancy was 67% and 60%, respectively. (4) Conclusions: Voriconazole is advocated for the treatment of invasive trichosporonosis given the intrinsic resistance to echinocandins and poor susceptibility to polyenes. Full article
14 pages, 2010 KiB  
Review
Invasive Saprochaete Infections: An Emerging Threat to Immunocompromised Patients
by Said El Zein, Joya-Rita Hindy and Souha S. Kanj
Pathogens 2020, 9(11), 922; https://doi.org/10.3390/pathogens9110922 - 7 Nov 2020
Cited by 22 | Viewed by 4420
Abstract
Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia. They have been associated with multiple hospital outbreaks mainly in Europe. In this article, we present a [...] Read more.
Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia. They have been associated with multiple hospital outbreaks mainly in Europe. In this article, we present a comprehensive review of the epidemiology, clinical presentation, diagnosis, antifungal susceptibility and treatment of these organisms. The diagnosis of invasive Saprochaete disease is challenging and relies primarily on the isolation of the fungi from blood or tissue samples. Both species are frequently misidentified as they are identical macroscopically and microscopically. Internal transcribed spacer sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry are useful tools for the differentiation of these fungi to a species level. Saprochaete spp. are intrinsically resistant to echinocandins and highly resistant to fluconazole. Current literature suggests the use of an amphotericin B formulation with or without flucytosine for the initial treatment of these infections. Treatment with extended spectrum azoles might be promising based on in vitro minimum inhibitory concentration values and results from case reports and case series. Source control and recovery of the immune system are crucial for successful therapy. Full article
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Other

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10 pages, 993 KiB  
Case Report
First Candida auris Outbreak during a COVID-19 Pandemic in a Tertiary-Care Center in Lebanon
by Fatima Allaw, Nada Kara Zahreddine, Ahmad Ibrahim, Joseph Tannous, Hussein Taleb, Abdul Rahman Bizri, Ghassan Dbaibo and Souha S. Kanj
Pathogens 2021, 10(2), 157; https://doi.org/10.3390/pathogens10020157 - 3 Feb 2021
Cited by 78 | Viewed by 6108
Abstract
Candida auris is an emerging fungal pathogen considered as a global health threat. Recently there has been growing concern regarding drug resistance, difficulty in identification, as well as problems with eradication. Although outbreaks have been reported throughout the globe including from several Arab [...] Read more.
Candida auris is an emerging fungal pathogen considered as a global health threat. Recently there has been growing concern regarding drug resistance, difficulty in identification, as well as problems with eradication. Although outbreaks have been reported throughout the globe including from several Arab countries, there were no previous reports from Lebanon. We herein report the first cases of C. auris infection from the American University of Beirut Medical Center, a tertiary care center in Lebanon describing the clinical features of the affected patients in addition to the infection control investigation and applied interventions to control the outbreak. Fourteen patients with C. auris infection/colonization identified using MALDI-TOF and VITEK 2- Compact system were reported over a period of 13 weeks. Patients were admitted to four separate critical care units. All of them came through the emergency room and had comorbid conditions. Half of the patients were infected with COVID-19 prior to isolation of the C. auris. C. auris was isolated from blood (two isolates), urine (three isolates), respiratory tract (10 isolates) and skin (one isolate). All the patients had received broad spectrum antibiotics prior to isolation of C. auris. Six patients received antifungal treatment, while the remaining eight patients were considered colonized. Environmental cultures were taken from all four units and failed to isolate the organism from any cultured surfaces. A series of interventions were initiated by the Infection Prevention and Control team to contain the outbreak. Rapid detection and reporting of cases are essential to prevent further hospital transmission. A national standardized infection control registry needs to be established to identify widespread colonization. Full article
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