Trichosporon species have been recognized as emerging opportunistic yeasts. They are commonly found on the skin and in the gastrointestinal flora of humans in temperate and semitropical climates (1). However, Trichosporon spp. can cause invasive and life-threatening fungal disease in immunocompromised hosts (2).

An exceedingly rare representative of this genus, Trichosporon japonicum, was first isolated in 1971 from the air of a microbiological laboratory in Japan and named by Sugita and Nakase in 1998 (3). The first clinical case was published in 2008, describing a T. japonicum related fungemia in a child with acute myeloid leukemia (AML) (4). In this report, we present a case of T. japonicum infection in a pediatric patient with refractory acute B cell lymphoblastic leukemia. Due to the rarity and growing importance of T. japonicum, here, we discuss a case which represents the second complete clinical and mycological resolution of T. japonicum blood infection amongst all case reports in literature to date (5).

The genus Trichosporon is composed of ~50 species which are widely present in nature (soil, air, seawater); 16 species have been identified as human pathogens of which T. japonicum has been isolated from different sources such as biopsy, skin, sputum, vaginal mucosa, bile, urine, pleural fluid, nails (6, 7). To date, only two clinical cases of T. japonicum isolated from blood samples have been described in the literature (5, 8). One case was reported in an adult with hematological malignancy who had undergone hematopoietic stem cell transplantation. The infection was catheter-related, which was later removed, and it contributed to death; treatment with liposomal AMB was not adequate (8). Additionally, the very first clinical case concerned a child with AML post bone marrow transplantation. Multiple yeasts were isolated from sputum cultures, therefore, she was treated with liposomal AMB and itraconazole. T. japonicum was only identified after her death (4). These cases illustrate the difficulty and delay in accurate diagnosis of T. japonicum infection along with the associated high mortality.

Little is known about factors related to T. japonicum virulence. Thermotolerance is a key feature of pathogenicity in yeasts as it allows them to switch from commensal to a pathogenic lifestyle (2, 7). Our results demonstrated that isolates of T. japonicum grow at 30°C as well as 37°C (Figure 2). Another known virulence factor of Trichosporon spp. is biofilm formation; it has been studied lately in relation to antifungal susceptibility (9). In this regard, Agirbasli et al. described a case of significant biofilm formation in T. japonicum (4).

Invasive Trichosporon infections often cause breakthrough fungemia with high mortality rate particularly in patients with hematological malignancies. These bloodstream infections are primarily associated with the presence of a CVC (10). However, it is somehow tricky to determine the source or portal of entry of the yeast in our case since the symptoms resolved and fungal BCs were repeatedly negative while the CVC was preserved until the end of the patient's hospital stay. In addition, no data suggested that the country of origin could be the reservoir of T. japonicum.

There is an increased resistance of Trichosporon spp. to antifungals as commonly reported in literature (11). Data obtained by Francisco et al. revealed that Trichosporon genus exhibits high resistance to AMB which seems to be species specific (12). In our case, the isolates of T. japonicum showed high MIC for echinocandins and fluconazole, medium for AMB and multiple azoles while the most effective drugs were isavuconazole and voriconazole. The infection occurred despite the use of AMB prophylaxis; however, it was successfully treated with voriconazole given in combination with AMB. Even though the most recent global guidelines give only marginal recommendation for adding AMB to voriconazole (13), the clinical decision to use such combination treatment was supported by the profound aplasia and impracticability of CVC removal.

In this study, despite the conservation of the CVC and the underlying disease progression, a clearance of the fungal infection was obtained with the combination AMB-voriconazole regimen. We therefore demonstrate the important role of voriconazole as a valuable therapeutic tool against Trichosporon infections. In conclusion, regardless of the disease stage and presence or absence of clinical manifestations, we recommend a regular focused investigation for fungi and yeasts in neutropenic patients, expanding it beyond the species and genera subject to most common diagnostic procedures.

The parents of the patient gave their consent to all the treatment and the publication of the case report. Unfortunately, the perspective of the patient and their parents were not explored due to their return to the country of origin and terminal condition of the patient.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Ethics Committee of the Bambino Gesù Children's Hospital. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.

SA-N, MA, AK, LM, MO, BL, and GM contributed to study design, data collection, analysis and interpretation, and drafting and writing the manuscript. FQ, MC, and PM supported the study with their role and clinical expertise. FL followed the patient outcome and critically revised the manuscript. CP and PB were responsible for funding acquisition and supervised the project. All authors approved the final version to be submitted for publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RH declared a past co-authorship with the authors FL and PM and the absence of any ongoing collaboration with any of the authors to the handling editor.

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