Rhinocerebral mucormycosis and Trichosporon asahii fungemia in a pediatric patient with acute lymphoblastic leukemia: a rare coinfection.

Mucormycosis is a rare life-threatening opportunistic infection, with rhinocerebral mucormycosis (ROCM) being the most common presentation. Trichosporon asahii is an emerging pathogen that often causes fatal infections in patients with underlying hematologic malignancies due to its high drug resistance. We report a rare case of concomitant rhinocerebral mucormycosis and T. asahii fungemia secondary to Pseudomonas aeruginosa sepsis in a patient with neutropenia and acute lymphoblastic leukemia. A boy aged one year and two months was diagnosed with B-cell acute lymphoblastic leukemia on January 10 and underwent three courses of regular chemotherapy. He experienced neutropenia for 154 days and was hospitalized for vomiting, diarrhea and fever for 3 days. The day after hospitalization, Pseudomonas aeruginosa was isolated by blood culture and ceftazidime/avibactam was administered. Extracorporeal Membrane Oxygenation (ECMO) was used to provide continuous extracorporeal respiration and circulation for the patient. On day 8, the patient developed T. asahii fungemia. On day 10, he presented with necrotizing skin caused by Rhizopus delemar. He was treated with liposomal amphotericin B for Rhizopus delemar and voriconazole for T. asahii infection. Unfortunately, his health deteriorated and he died on day 11 due to the rapid progression of the infection and multiple organ failure. The management and treatment of such a complex infection requires a multidisciplinary approach and close monitoring of the patient's condition. Therefore, it is imperative to continue to research and report rare cases such as this to further understand the complexities of mucormycosis and trichosporidiosis coinfection and improve patient outcomes.

Photodynamic therapy successfully treats refractory onychomycosis caused by Trichosporon asahii: a case report.

Onychomycosis, a fungal infection affecting the nail, is characterized by discoloration and thickening of the nail plate and is the most prevalent nail infection globally. We present a case of onychomycosis caused by Trichosporon asahii, a less common etiology. Notably, the patient was successfully treated with a non-traditional antibacterial approach, photodynamic therapy, which has been infrequently documented in the literature for such infections.

Erythematous ulcero-proliferative exophytic lesion in an oral squamous cell carcinoma patient- An unusual case of Trichosporonosis.

ABSTRACT: The emergence of non-Candida yeast infections in humans has been increasingly recognized over the last decades. Trichosporon is the third most isolated non-candidal yeast in patients with an impaired immune system. We report a rare case of Trichosporon asahii causing erythematous oral lesion in a patient with squamous cell carcinoma. Our case highlights the occurrence of unusual yeast pathogens in patients with cancer with typical clinical presentations and warrants suspicion of fungal etiology to prevent misdiagnosis of trichosporonosis.

Skin Manifestations of Micafungin Breakthrough Disseminated Trichosporonosis in Acute Megakaryoblastic Leukemia.

Disseminated trichosporonosis is a rare fungal infection whose risk factors are hematological malignancies and neutropenia. Recently, breakthrough Trichosporon infections after administration of micafungin, the first-line systemic antifungal agent in compromised hosts, have been widely recognized. A man in his seventies about 1 month into chemotherapy for acute megakaryoblastic leukemia presented with a worsening fever and dyspnea. The patient was being administered with empirical micafungin therapy for suspected candidiasis. As the symptoms progressed, scattered erythema appeared on the trunk, some with a dark red vesicle at the center. Blood cultures identified Trichosporon asahii, as did the specimen of the skin biopsy. On the basis also of the presence of pneumonia on chest computed tomography, we confirmed the diagnosis of disseminated trichosporonosis and changed the antifungal agent from micafungin to voriconazole. Blood culture turned out to be negative 1 month after administrating voriconazole. However, the patient died of the leukemia. Our review of previous reports on cutaneous manifestations of disseminated trichosporonosis revealed that despite their morphological diversity, erythema with a red papule or vesicle at the center, implying necrosis, was also observed in previous cases. Our case report suggests that dermatologists should be aware of skin manifestations of disseminated trichosporonosis after micafungin administration, especially in cases of hematological malignancies.

Intergenic spacer (IGS-1) region sequence-based identification, genotypic analysis, and antifungal susceptibility of clinical Trichosporon species.

OBJECTIVES: Molecular genotyping of Trichosporon species using intergenic spacer region (IGS-1) sequencing and antifungal drug susceptibility testing of T. asahii clinical isolates from Indian patients. MATERIALS AND METHODS: Fifty-five Trichosporon strains were characterized using IGS-1 sequencing from 2006 to 2018 and tested against 5 antifungals using CLSI M27-A3 guidelines. RESULTS: In this study, broad-spectrum antibiotics with steroids, catheters, and ICU stays were major underlying risk factors. These cases were most commonly associated with diabetes (type-2), chronic obstructive pulmonary disease, and hypertension. Out of fifty-five isolates, 47 (85%) were identified as T. asahii, and the remaining 6 were T. inkin (11%) and 2 were Cutaneotrichosporon dermatis (3.6%). The most common genotype of T. asahii was G3 (22; 49%) subsequently G4 (12; 23%), G1 (8; 17%), and G7 (2; 4%). One new genotype of T asahii was found in addition to the fifteen already known genotypes. Indian T. asahii isolates showed a low level of amphotericin B (range 0.06-4 â€‹mg/l) resistance but relatively higher in fluconazole (range 0.25-64 â€‹mg/l). Although, comparatively low MIC ranges were found in the case of voriconazole (0.03-1 â€‹mg/l), posaconazole (0.06-1 â€‹mg/l) and itraconazole (0.06-1 â€‹mg/l). Voriconazole appeared to be the most active drug in T. asahii isolates. The MICs for all the drugs were comparatively lower in the case of non-Trichosporon asahii strains. CONCLUSION: T. asahii was the most common Trichosporon isolate. Speciation is necessary for optimal antifungal therapy. Voriconazole-based treatment, Steroids, removal of catheters and control of underlying conditions results in positive outcomes.

Differences of clinical characteristics and outcome in proven invasive Trichosporon infections caused by asahii and non-asahii species.

BACKGROUND: Trichosporon is an emerging yeast that causes invasive infections in immunocompromised patients experiencing prolonged hospitalisation, indwelling venous catheters and neutropenia. METHODS: This retrospective observational cohort study analysed invasive Trichosporon infections (ITIs) occurring between January 2005 and December 2022 at three tertiary hospitals and compared the clinical characteristics and prognostic factors of ITIs caused by Trichosporon asahii and non-T. asahii spp. After evaluating 1067 clinical isolates, we identified 46 patients with proven ITIs, defined as cases in which Trichosporon was isolated from blood, cerebrospinal fluid, or sterile tissues. RESULTS: The patients were separated into T. asahii and non-T. asahii groups containing 25 and 21 patients, respectively, all of which except one were immunocompromised. During this period, both the number of clinical isolates and patients with ITIs (mainly T. asahii) increased; whereas, cases involving non-T. asahii spp. decreased. Compared with the non-T. asahii group, the T. asahii group had more patients with multiple catheters (84% vs. 33%, p = .001) and those receiving renal replacement therapy (48% vs. 14%, p = .005). The all-cause 28-day mortality rate after ITI in the T. asahii group (44%) was significantly higher than in the non-T. asahii group (10%, Log-rank p = .014). The multivariate Cox regression model revealed that T. asahii (reference, non-T. asahii spp.; aHR = 4.3; 95% CI = 1.2-15.2, p = .024) and neutropenia for 5 days or more (aHR = 2.2, 95% CI = 1.5-3.6, p = .035) were independent factors in the 28-day mortality after ITI. CONCLUSION: The proven ITIs due to T. asahii produced more unfavourable outcomes compared with ITIs caused by non-T. asahii spp.

Infección invasora por Trichosporon asahii en un niño con leucemia linfoblástica aguda / Invasive fungal infection by Trichosporon asahii in a pediatric patient with acute lymphoblastic leukemia: A case report and review of the literature

La enfermedad fúngica invasora (EFI) es una de las principales causas de morbimortalidad en los pacientes pediátricos inmunocom- prometidos. Los hongos que con mayor frecuencia causan EFI en este grupo de pacientes corresponden a especies de Candida y Aspergillus. Sin embargo, en los últimos años se ha descrito un aumento de patógenos no clásicos, tales como Fusarium, Scedosporium, Mucorales, Cryptococcus, Trichosporon, entre otros. Se presenta un caso de EFI por Trichosporon asahii en un preescolar con una leucemia linfo- blástica aguda en quimioterapia de inducción. Además, se presenta una revisión actualizada de la literatura especializada, con énfasis en la importancia del diagnóstico precoz y el tratamiento antifúngico específico.

Invasive fungal disease (IFD) is one of the leading causes of morbidity and death among immunosuppressed pediatric patients. The fungi that most frequently cause IFD in this group of patients correspond to Candida and Aspergillus species, however, in recent years an increase in non-classical pathogens, such as Fusarium, Scedosporium, Mucorales, Cryptococcus, Trichosporon, among others. A case of invasive fungal disease caused by Trichosporon asahii is presented in a preschool patient with acute lymphoblastic leukemia in induction stage. This review highlights the importance of active search for pathogens in immunosuppressed patients, and proposes a specific treatment.

Antifungal Activity and Potential Action Mechanism of Allicin against Trichosporon asahii.

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. In vitro, allicin inhibited the growth of T. asahii planktonic cells and biofilm cells significantly. In vivo, 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. IMPORTANCE 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 in vitro antifungal activity and potential in vivo protective effects. In addition, transcriptome sequencing provided valuable insights into the antifungal effects of allicin.

Tacrolimus inhibits stress responses and hyphal formation via the calcineurin signaling pathway in Trichosporon asahii.

The pathogenic fungus Trichosporon asahii causes fatal deep-seated mycosis in immunocompromised patients. Calcineurin, which is widely conserved in eukaryotes, regulates cell growth and various stress responses in fungi. Tacrolimus (FK506), a calcineurin inhibitor, induces sensitivity to compounds that cause stress on the cell membrane and cell wall integrity. In this study, we demonstrated that FK506 affects stress responses and hyphal formation in T. asahii. In silico structural analysis revealed that amino acid residues in the binding site of the calcineurin-FKBP12 complex that interact with FK506 are conserved in T. asahii. The growth of T. asahii was delayed by FK506 in the presence of SDS or Congo red but not in the presence of calcium chloride. FK506 also inhibited hyphal formation in T. asahii. A mutant deficient of the cnb gene, which encodes the regulatory subunit B of calcineurin, exhibited stress sensitivities on exposure to SDS and Congo red and reduced the hyphal forming ability of T. asahii. In the cnb-deficient mutant, FK506 did not increase the stress sensitivity or reduce hyphal forming ability. These results suggest that FK506 affects stress responses and hyphal formation in T. asahii via the calcineurin signaling pathway.

Possible Trichosporon asahii urinary tract infection in a critically ill COVID-19 patient.

BACKGROUND: Trichosporon asahii, an emerging fungal pathogen, has been frequently associated with invasive infections in critically ill patients. CASE REPORT: A 74-year-old male patient diagnosed with COVID-19 was admitted to an Intensive Care Unit (ICU). During hospitalization, the patient displayed episodes of bacteremia by Staphylococcus haemolyticus and a possible urinary tract infection by T. asahii. While the bacterial infection was successfully treated using broad-spectrum antibiotics, the fungal infection in the urinary tract was unsuccessfully treated with anidulafungin and persisted until the patient died. CONCLUSIONS: With the evolving COVID-19 pandemic, invasive fungal infections have been increasingly reported, mainly after taking immunosuppressant drugs associated with long-term broad-spectrum antibiotic therapy. Although Candida and Aspergillus are still the most prevalent invasive fungi, T. asahii and other agents have emerged in critically ill patients. Therefore, a proper surveillance and diagnosing any fungal infection are paramount, particularly in COVID-19 immunocompromised populations.

Trichosporon asahii causing subcutaneous mycoses in an immunocompetent patient: case report and a minireview.

Trichosporon spp. are a constituent of the normal flora of humans that can cause both superficial and invasive infections, mainly in immunocompromised and immunocompetent hosts, respectively. Herein, we a report of Trichosporon asahii causing subcutaneous fungal infection (SFI) in an immunocompetent patient after carpal tunnel surgery. Although susceptible to fluconazole, the treatment of SFI failed even using high doses of this azole. The skin lesion improved following the administration of voriconazole. We conducted a literature minireview searching reports on SFI in immunocompetent patients to check for epidemiological, diagnostic, therapeutic, and outcome characteristics. A total of 32 cases were reported. Despite being uncommon, the clinical suspicion and early diagnosis of SFI in immunocompetent patients undergoing previous surgery are important. Our study indicated that the azoles are the most active antifungal agents against Trichosporon spp., except for fluconazole, and voriconazole can be considered the first therapeutic option.

EQUAL Trichosporon Score 2022: an ECMM score to measure QUALity of the clinical management of invasive Trichosporon infections.

BACKGROUND: Invasive infections due to Trichosporon spp. are life-threatening opportunistic fungal infections that require complex clinical management. Guidelines assist clinicians but can be challenging to comply with. OBJECTIVES: To develop a scoring tool to facilitate and quantify adherence to current guideline recommendations for invasive trichosporonosis. METHODS: We reviewed the current guideline for managing rare yeast infections (ECMM, ISHAM and ASM). The most important recommendations for diagnosis, treatment and follow-up were assembled and weighted according to their strength of recommendation and level of evidence. Additional items considered highly relevant for clinical management were also included. RESULTS: The resulting EQUAL Trichosporon Score 2022 comprises 18 items, with a maximum score of 39 points. For diagnostics, seven or eight items, depending on whether organ involvement is present or not, apply, resulting in a maximum of 18 or 21 points. Recommendations on diagnostics include imaging, infectious diseases expert consultation, culture, microscopy, molecular techniques, histopathology, and susceptibility testing. For treatment, six recommendations with a maximum of ten points were identified, with two additional points for organ involvement and one point for second-line treatment in uncontrolled disease. Treatment recommendations include immediate initiation, source control, pharmacological treatment, therapeutic drug monitoring, treatment duration and surgical intervention. Follow-up comprises two items with five points maximum, covering follow-up blood cultures and imaging. CONCLUSIONS: The EQUAL Trichosporon Score weighs and aggregates factors recommended for optimal management of Trichosporon infections. It provides a tool for antifungal stewardship as well as for measuring guideline adherence, but remains to be correlated with patient outcomes.

Breakthrough Trichosporon asahii in a Patient With New Diagnosis B-ALL on Echinocandin Prophylaxis: A Case Report.

Invasive fungal disease is a difficult to diagnose complication of therapy in patients with hematologic malignancy. Antifungal prophylaxis is recommended in high-risk populations, but its use in other populations is less clear. This brief report describes a patient with Trisomy 21 on caspofungin prophylaxis who died of disseminated Trichosporon asahii during induction therapy for new diagnosis low-risk B-cell acute lymphoblastic leukemia, accompanied by a review of similar cases in the literature. Her case highlights the utility of relatively novel diagnostic modalities and reinforces the need for caution in placing patients on antifungal prophylaxis.

JMM Profile: Trichosporon yeasts: from superficial pathogen to threat for haematological-neutropenic patients.

Trichosporon yeasts are classical agents of superficial mycoses, and they are ranked as the first to second predominant basidiomycetous yeast able to cause invasive infections. The clinical presentation of Trichosporon infections varies with the affected anatomical site, with fungaemia present in the majority of invasive trichosporonosis cases. Only a limited number of antifungal compounds can be used to treat Trichosporon infections. Azoles are the first choice due to their intrinsic resistance to echinocandins. Better laboratory methods and up-to-date databases of commercial platforms are required to improve identification, susceptibility testing and surveillance of this potentially threating infection.

Orthopedic infections due to Trichosporon species: Case series and literature review.

Reports of orthopedic fungal infections caused by Trichosporon species are extremely scarce, thus we aimed to describe a case series and review the cases published in the literature. Patients were retrospectively included if a previous culture of bone, joint, or soft tissues had resulted positive for Trichosporon species along with a clinical diagnosis of an orthopedic infection. Eight patients were included with diverse orthopedic conditions, most of them cases of osteomyelitis. The main isolated species was Trichosporon asahii. All patients were treated with antifungals, mainly voriconazole, and surgical management, resulting in high rates of clinical improvement and low associated mortality.

Reports of orthopedic infections caused by Trichosporon species are scarce. We described a case series of orthopedic infections caused by Trichosporon species and reviewed the previous published cases in the literature. We observed a high rate of clinical improvement and a low associated mortality.