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Therapeutic Advances in Infectious... 2024Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell... (Review)
Review
Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell transplant recipients but also patients with malignancies or autoimmune diseases receiving immunomodulatory therapies, such as Bruton Tyrosine Kinase (BTK) inhibitor. Their attributable mortality remains elevated, part of which is a contribution from globally emerging resistance in both molds and yeasts. Because antifungal susceptibility test results are often unavailable or delayed, empiric and tailored antifungal approaches including choice of agent(s) and use of combination therapy are heterogeneous and often based on clinician experience with knowledge of host's net state of immunosuppression, prior antifungal exposure, antifungal side effects and interaction profile, clinical severity of disease including site(s) of infection and local resistance data. In this review, we aim to summarize previous recommendations and most recent literature on treatment of invasive mold and yeast infections in adults to guide optimal evidence-based therapeutic approaches. We review the recent data that support use of available antifungal agents, including the different triazoles that have now been studied in comparison to previously preferred agents. We discuss management of complex infections with specific emerging fungi such as spp., spp., , and . We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies.
PubMed: 38249542
DOI: 10.1177/20499361231224980 -
Frontiers in Cellular and Infection... 2021Persister cells are metabolically inactive dormant cells that lie within microbial biofilms. They are phenotypic variants highly tolerant to antimicrobials and,...
Persister cells are metabolically inactive dormant cells that lie within microbial biofilms. They are phenotypic variants highly tolerant to antimicrobials and, therefore, associated with recalcitrant infections. In the present study, we investigated if and are able to produce persister cells. spp. are ubiquitous fungi, commonly found as commensals of the human skin and gut microbiota, and have been increasingly reported as agents of fungemia in immunocompromised patients. Biofilms derived from clinical strains of (n=5) and (n=7) were formed in flat-bottomed microtiter plates and incubated at 35°C for 48 h, treated with 100 μg/ml amphotericin B (AMB) and incubated at 35°C for additional 24 h. Biofilms were scraped from the wells and persister cells were assayed for susceptibility to AMB. Additionally, we investigated if these persister cells were able to generate new biofilms and studied their ultrastructure and AMB susceptibility. Persister cells were detected in both and biofilms and showed tolerance to high doses of AMB (up to 256 times higher than the minimum inhibitory concentration). Persister cells were able to generate biofilms, however they presented reduced biomass and metabolic activity, and reduced tolerance to AMB, in comparison to biofilm growth control. The present study describes the occurrence of persister cells in spp. and suggests their role in the reduced AMB susceptibility of . and biofilms.
Topics: Antifungal Agents; Basidiomycota; Biofilms; Humans; Microbial Sensitivity Tests; Trichosporon
PubMed: 33968802
DOI: 10.3389/fcimb.2021.645812 -
Clinical Microbiology and Infection :... Apr 2014The mortality associated with invasive fungal infections remains high with that involving rare yeast pathogens other than Candida being no exception. This is in part due...
The mortality associated with invasive fungal infections remains high with that involving rare yeast pathogens other than Candida being no exception. This is in part due to the severe underlying conditions typically predisposing patients to these healthcare-related infections (most often severe neutropenia in patients with haematological malignancies), and in part due to the often challenging intrinsic susceptibility pattern of the pathogens that potentially leads to delayed appropriate antifungal treatment. A panel of experts of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and the European Confederation of Medical Mycology (ECMM) undertook a data review and compiled guidelines for the diagnostic tests and procedures for detection and management of rare invasive yeast infections. The rare yeast pathogens were defined and limited to the following genera/species: Cryptococcus adeliensis, Cryptococcus albidus, Cryptococcus curvatus, Cryptococcus flavescens, Cryptococcus laurentii and Cryptococcus uniguttulatus (often published under the name Filobasidium uniguttulatum), Malassezia furfur, Malassezia globosa, Malassezia pachydermatis and Malassezia restricta, Pseudozyma spp., Rhodotorula glutinis, Rhodotorula minuta and Rhodotorula mucilaginosa, Sporobolomyces spp., Trichosporon asahii, Trichosporon asteroides, Trichosporon dermatis, Trichosporon inkin, Trichosporon jirovecii, Trichosporon loubieri, Trichosporon mucoides and Trichosporon mycotoxinivorans and ascomycetous ones: Geotrichum candidum, Kodamaea ohmeri, Saccharomyces cerevisiae (incl. S. boulardii) and Saprochaete capitatae (Magnusiomyces (Blastoschizomyces) capitatus formerly named Trichosporon capitatum or Geotrichum (Dipodascus) capitatum) and Saprochaete clavata. Recommendations about the microbiological investigation and detection of invasive infection were made and current knowledge on the most appropriate antifungal and supportive treatment was reviewed. In addition, remarks about antifungal susceptibility testing were made.
Topics: Humans; Mycoses; Rare Diseases
PubMed: 24102785
DOI: 10.1111/1469-0691.12360 -
Microbiology Spectrum Jun 2023Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019...
Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019 (COVID-19) poses an increasing fungal infection burden caused by T. asahii. Allicin is the main biologically active component with broad-spectrum antimicrobial activity in garlic. In this study, we performed an in-depth analysis of the antifungal characteristics of allicin against T. asahii based on physiological, cytological, and transcriptomic assessments. , allicin inhibited the growth of T. asahii planktonic cells and biofilm cells significantly. , allicin improved the mean survival time of mice with systemic trichosporonosis and reduced tissue fungal burden. Electron microscopy observations clearly demonstrated damage to T. asahii cell morphology and ultrastructure caused by allicin. Furthermore, allicin increased intracellular reactive oxygen species (ROS) accumulation, leading to oxidative stress damage in T. asahii cells. Transcriptome analysis showed that allicin treatment disturbed the biosynthesis of cell membrane and cell wall, glucose catabolism, and oxidative stress. The overexpression of multiple antioxidant enzymes and transporters may also place an additional burden on cells, causing them to collapse. Our findings shed new light on the potential of allicin as an alternative treatment strategy for trichosporonosis. Systemic infection caused by T. asahii has recently been recognized as an important cause of mortality in hospitalized COVID-19 patients. Invasive trichosporonosis remains a significant challenge for clinicians, due to the limited therapeutic options. The present work suggests that allicin holds great potential as a therapeutic candidate for T. asahii infection. Allicin demonstrated potent antifungal activity and potential protective effects. In addition, transcriptome sequencing provided valuable insights into the antifungal effects of allicin.
Topics: Animals; Mice; Antifungal Agents; Trichosporonosis; Trichosporon; COVID-19; Antioxidants
PubMed: 37199655
DOI: 10.1128/spectrum.00907-23 -
Antimicrobial Agents and Chemotherapy Feb 2021is an opportunistic fungal pathogen that can cause severe infections with high mortality rates. Azole derivatives are the best-targeted therapy for invasive...
Correlation of Genotypes with Anatomical Sites and Antifungal Susceptibility Profiles: Data Analyses from 284 Isolates Collected in the Last 22 Years across 24 Medical Centers.
is an opportunistic fungal pathogen that can cause severe infections with high mortality rates. Azole derivatives are the best-targeted therapy for invasive infections, but azole-resistant isolates have been reported. To investigate peculiarities in the antifungal susceptibility profile (ASP) of clinical isolates, we analyzed the genotype distribution, isolation sources, and ASP of 284 strains collected from 1997 to 2019 in different Brazilian medical centers. Species identification and genotype characterization were performed by analysis of the intergenic spacer (IGS1) region of the ribosomal DNA (rDNA). Antifungal susceptibility testing (AST) for amphotericin B and azoles was with the CLSI M27, 4th edition, microdilution broth method. Trends in the ASP of Brazilian isolates were investigated using epidemiological cutoff values. Five different genotypes were found among the 284 isolates tested (G1, 76%; G3, 10%; G4, 3%; G5, 7%; and G7, 4%). The isolates were collected mainly from urine (55%) and blood/catheter tip samples (25%) where G1 was the most frequent genotype found ( < 0.05). The G7 isolates exhibited the highest MIC values for azoles compared to those for the other genotypes ( < 0.05). Genotype 7 isolates also contributed to the increasing rates of voriconazole non-wild-type isolates found in recent years ( = 0.02). No significant differences were found among the AST results generated by isolates cultured from different anatomical sites. Monitoring genotype distributions and antifungal susceptibility profiles is warranted to prevent the spread of azole-resistant isolates.
Topics: Antifungal Agents; Basidiomycota; Brazil; DNA, Fungal; Data Analysis; Genotype; Humans; Microbial Sensitivity Tests; Trichosporon; Trichosporonosis
PubMed: 33318016
DOI: 10.1128/AAC.01104-20 -
Cureus Aug 2021species are basidiomycetous yeast-like organisms found ubiquitous in nature. They are increasingly been recognized as opportunistic pathogens capable of causing... (Review)
Review
species are basidiomycetous yeast-like organisms found ubiquitous in nature. They are increasingly been recognized as opportunistic pathogens capable of causing life-threatening invasive diseases (trichosporonosis), especially in immuno-suppressed patients and rarely in immuno-competent patients too. Earlier multiple members of the genus were clubbed together as but after the advent of molecular techniques, more than 50 different subspecies and around 16 different strains causing human diseases are reported. It is known to cause a wide range of diseases, from superficial to probable and proven invasive diseases to summer hypersensitivity. The ability of strains to form biofilms on implanted devices, glucuronoxylomannan in their cell walls, and production of proteases and lipases lead to the virulence of this genus. This ubiquitous fungus exhibits intrinsic resistance to echinocandins, variable minimum inhibitory concentrations (MIC) for amphotericin B, and moderate susceptibility to fluconazole and Itraconazole, which are the commonly used anti-fungal agents for any invasive fungal infections which lead to the re-emergence of this notorious yet neglected pathogen and hence the reports of breakthrough infections among patients receiving these antifungals. This review is to understand the epidemiological, clinical details, and antifungal susceptibility pattern of various infections and it highlights the importance of early detection and treatment for this emerging yeast and also will add to the ongoing surveillance for the anti-fungal susceptibility pattern for this fungus.
PubMed: 34567886
DOI: 10.7759/cureus.17345 -
Pathogens (Basel, Switzerland) Feb 2022(1) Background: species have emerged as important opportunistic fungal pathogens, with being the leading and most frequent cause of invasive disease. (2) Methods: We... (Review)
Review
(1) Background: species have emerged as important opportunistic fungal pathogens, with 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 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. 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.
PubMed: 35215184
DOI: 10.3390/pathogens11020242 -
Mycoses Aug 2021To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients.
OBJECTIVES
To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients.
METHODS
From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing.
RESULTS
Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives.
CONCLUSIONS
Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.
Topics: Adrenal Cortex Hormones; Aged; Antifungal Agents; Basidiomycota; Brazil; COVID-19; Candidemia; Female; Fungemia; Haplotypes; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Risk Factors; Superinfection; Trichosporonosis
PubMed: 34091966
DOI: 10.1111/myc.13333 -
Antibiotics (Basel, Switzerland) Jul 2023spp. endocarditis is a severe and hard-to-treat infection. Immunosuppressed subjects and carriers of prosthetic valves or intracardiac devices are at risk. This article... (Review)
Review
spp. endocarditis is a severe and hard-to-treat infection. Immunosuppressed subjects and carriers of prosthetic valves or intracardiac devices are at risk. This article presents the case of an immunocompetent 74-year-old man affected by endocarditis of the prosthetic aortic valve. After Bentall surgery, cultures of the removed valve demonstrated as the etiological agent. The patient was treated with amphotericin B at first and subsequently with fluconazole. Given the fragility of the patient and the aggressiveness of the pathogen, life-long prophylactic therapy with fluconazole was prescribed. After 5 years follow-up, no drug-related toxicities were reported and the patient never showed any signs of recurrence. The review of the literature illustrates that spp. endocarditis may present even many years after heart surgery, and it is often associated with massive valve vegetations, severe embolic complications, and unfavorable outcome. Due to the absence of international guidelines, there is no unanimous therapeutic approach, but amphotericin B and azoles are usually prescribed. Additionally, a prompt surgical intervention seems to be of paramount importance. When dealing with a life-threatening disease, such as mycotic endocarditis of prosthetic valves, it is essential to consider and treat even rare etiological agents such as spp.
PubMed: 37508277
DOI: 10.3390/antibiotics12071181 -
Journal of Fungi (Basel, Switzerland) Jul 2023Systemic infections caused by rare yeasts are increasing given the rise in immunocompromised or seriously ill patients. Even though globally, the clinical significance... (Review)
Review
Systemic infections caused by rare yeasts are increasing given the rise in immunocompromised or seriously ill patients. Even though globally, the clinical significance of these emerging opportunistic yeasts is increasingly being recognized, less is known about the epidemiology of rare yeasts in Latin America. This review collects, analyzes, and contributes demographic and clinical data from 495 cases of infection caused by rare yeasts in the region. Among all cases, 32 species of rare yeasts, distributed in 12 genera, have been reported in 8 Latin American countries, with (49.5%), (11.1%), and (7.8%) the most common species found. Patients were mostly male (58.3%), from neonates to 84 years of age. Statistically, surgery and antibiotic use were associated with higher rates of infections, while central venous catheter, leukemia, and cancer were associated with higher rates of infections. From all cases, fungemia was the predominant diagnosis (50.3%). Patients were mostly treated with amphotericin B (58.7%). Crude mortality was 40.8%, with a higher risk of death from fungemia and infections. Culture was the main diagnostic methodology. Antifungal resistance to one or more drugs was reported in various species of rare yeasts.
PubMed: 37504735
DOI: 10.3390/jof9070747