Invasive trichosporonosis in children: a 10-year experience from a tertiary care center in Türkiye

Abstract

Invasive fungal infections, particularly those caused by Trichosporon species, have increasingly been observed in recent years, leading to high morbidity and mortality rates in immunosuppressed patients. Trichosporon asahii is the most common species associated with systemic infections. Despite their clinical importance, especially in pediatric patients, information remains limited. This study aims to investigate the clinical characteristics, comorbidities, treatment methods, and outcomes of invasive Trichosporon infections diagnosed over 10 years at a university hospital. The medical records of patients diagnosed with invasive Trichosporon infections between December 2013 and January 2024 at our center were retrospectively reviewed. A total of 12 cases of invasive Trichosporon infection were examined during the study period. In 75% of these cases, the isolated species was T. asahii. Underlying comorbidities were present in 33.3% of the patients, with hematologic malignancies in 33.3% and immunodeficiency in 33.3%. Among the treatment strategies, 12.5% of the patients received voriconazole monotherapy, and 37.5% received a combination of voriconazole and antifungal therapy, with the most common combination being voriconazole and liposomal L-AmB. The overall mortality rate was 41.7%, with 7-day mortality at 8.3% and 30-day mortality at 25%. Invasive Trichosporon infections are serious infections with a high mortality risk in immunocompromised patients. Early diagnosis, timely initiation of appropriate antifungal therapy, and management of underlying comorbidities are critical for improving patient outcomes. Due to the limited number of cases, further research in this field is needed.

Introduction

The incidence of invasive fungal infections is increasing both in our country and globally [1–3]. The main reasons for this increase include aggressive chemotherapy protocols used in cancer and organ transplant patients, prolonged neutropenia, invasive procedures such as central venous catheters, the rising number of immunosuppressed patients (bone marrow and solid organ transplants, HIV infection), and antifungal/antimicrobial prophylaxis or treatment practices [1]. Additionally, the identification of rarer pathogens, owing to the advancement of laboratory diagnostic methods, has contributed to changes in epidemiological data [2, 3].

Invasive fungal infections, particularly in immunosuppressed patients, are significant causes of morbidity and mortality. Trichosporon species are basidiomycetous, yeast-like fungi that are commonly found in nature, in soil, aquatic environments, and plants, and are also part of the normal flora in humans, residing in the gastrointestinal, genitourinary, respiratory systems, and skin [4–6]. Trichosporon species can cause invasive infections by leading to skin, eye, lung, kidney infections, and rarely, systemic fungemia [5].

In immunocompromised patients, especially those with hematologic malignancies, invasive infections caused by Trichosporon species are associated with significant morbidity and mortality rates [6]. These infections are most commonly observed in patients with febrile neutropenia [7]. The risk of invasive infections increases in patients with intravascular catheters, especially those with underlying malignancy, immunodeficiency, and those receiving long-term broad-spectrum antibiotic therapy [8–10]. Due to the rarity of Trichosporon infections in children and diagnostic challenges, the literature mostly consists of small case series. This study aims to investigate the demographic characteristics, underlying risk factors, treatment approaches, and clinical outcomes of invasive Trichosporon infections specifically in the pediatric population.

Materials and methods

Study design and setting

This retrospective study was conducted at Çukurova University Faculty of Medicine, Balcalı Hospital, a tertiary university hospital in Türkiye. The study period spanned from December 2013 to January 2024.

Inclusion and exclusion criteria

Patients under 18 years of age who had Trichosporon spp. growth in at least one of the following cultures—blood, catheter, tracheal aspirate, sputum, or peritoneal fluid—were evaluated.

Patients were included if they met the following criteria:

• Trichosporon spp. growth in sterile body fluids or blood.

• Clinical and/or laboratory evidence of systemic infection with multi-organ involvement, consistent with invasive fungal infection.

Exclusion criteria were:

• Age above 18 years.

• Inaccessibility of medical records or insufficient clinical data.

• Growth of Trichosporon spp. in non-sterile sites (e.g., throat, tracheal aspirate, or urine) without clinical evidence of infection, considered colonization.

Method and data collection

A total of 20 patients with Trichosporon spp. growth were identified. Based on clinical and laboratory assessment, eight patients were excluded due to likely colonization (three from tracheal aspirates, three from throat swabs, and two from urine cultures). Twelve pediatric patients were accepted as having invasive Trichosporonosis.

Patients were evaluated for Trichosporon infection due to clinical suspicion based on persistent fever unresponsive to broad-spectrum antibiotics, neutropenia (ANC <500/mm³), presence of central venous catheters, prolonged intensive care unit stay, immunosuppressive conditions (such as hematologic malignancies or chemotherapy), and signs of systemic infection such as hypotension, respiratory distress, or organ dysfunction. Fungal cultures were obtained as part of the diagnostic work-up in these clinical scenarios.

Demographic characteristics, clinical findings, underlying diseases, risk factors, antifungal susceptibility test results, treatments received, and outcomes (overall mortality, 7-day and 30-day mortality) were collected from hospital’s electronic health record system and, where needed, from archived physical patient files. Neutropenia was defined as an absolute neutrophil count (ANC) below 500 cells/mm³.

Microbiological identification and susceptibility testing

Yeast colonies grown on Sabouraud Dextrose Agar were first examined with Gram staining. Identification of Trichosporon species was performed using the VITEK^® 2 YST Identification Card with a 2.0 McFarland yeast suspension, achieving a probability of 97%–99%. Candida albicans ATCC 14053 was used as the quality control strain for identification.

Antifungal susceptibility was assessed using the VITEK^® 2 AST-YS08 Card. Minimum inhibitory concentration (MIC) values were recorded, although there are currently no established MIC breakpoints for Trichosporon spp. For quality control of antifungal testing, Candida parapsilosis ATCC 22019 was used.

Ethical approval

Ethical approval for this study was obtained from the ethics committee of the Çukurova University Faculty of Medicine(Meeting number: 151, 03 January 2025).

Statistical analysis

The statistical analysis of the study was performed using the Statistical Package for Social Sciences (SPSS) version 20 (IBM Corp., Armonk, NY, USA). Descriptive statistics for parametric numerical data were calculated as mean ± standard deviation, while non-parametric data were expressed as median (minimum–maximum). Categorical data were presented as percentages (%).

Results

Patient selection and demographics

A total of 20 patient records were initially reviewed. In three patients, Trichosporon spp. was isolated from tracheal aspirate cultures, in three from throat swabs, and in two from urine cultures. Based on clinical and laboratory findings, these eight cases were determined to represent colonization rather than invasive infection and were therefore excluded from the analysis. Ultimately, 12 patients who met the criteria for invasive Trichosporon infection were included in the study. Of these, 7 (58.3%) were male, and the median age was 82.5 months (min: 2 months, max: 158 months) (Table 1).

Table 1.

Demographic, clinical, and treatment characteristics of patients

Gender
Female, n (%)	5 (42.7)
Male, n (%)	7 (58.3)
Age (months)a	82.5 (2, 158)
Length of hospital stay (days)a	44.5 (16, 76)
PICUb admission, n (%)	7 (58.3%)
PICU stay duration (days)a	28 (3, 64)
Presence of neutropenia, n (%)	4
Overall mortality, n (%)	5 (41.7%)
7-day mortality, n (%)	1 (8.3%)
30-day mortality, n (%)	3 (25%)
Presence of central catheter, n (%)	11 (91.7%)
Central catheter duration (days)a	24 (5, 42)
Antifungal treatment, n (%)
Monotherapy	5 (41.7%)
Combination therapy	7 (58.3%)
Duration of antifungal treatment (days)a	16 (7, 30)
Antifungal prophylaxis after treatment, n (%)	3 (25%)

^aMedian (minimum, maximum).

^bPediatric intensive care unit.

Sites of infection and microbiological findings

In one patient, Trichosporon asahii growth was found in peritoneal fluid, while in the other 11, growth was detected in blood and/or catheter cultures (Table 2). The distribution of species was as follows: T. asahii (n = 9, 75%), Trichosporon mucoides (n = 2, 16.7%), and Trichosporon spp. (n = 1, 8.3%). Eleven patients had Trichosporon-related fungemia, seven of which were catheter-associated. One patient presented with peritonitis. After catheter placement, growth was observed at a median of 24 days (range: 5–42 days). The median day of culture positivity was the 14th day of hospitalization (range: 1–30 days). The first negative culture after treatment was obtained at a median of 6 days (range: 3–16 days). One patient (Case 9) died before a negative culture result could be obtained.

Table 2.

Demographic and clinical characteristics of the cases

Case no.	Age (months)	Gender	Year of admission	Underlying disease	Growth culture area	Simultaneous catheter growth	Pre-culture treatment	Post-culture treatment	Outcome
1	72	Male	2013	ALLa	Blood	None	None	Voriconazole	Discharged
2	100	Male	2015	ALLa	Blood	None	Caspofungin	Voriconazole, Ambisome	Exitus
3	30	Female	2015	Muscular dystrophy	Blood	None	Fluconazole	Voriconazole, Ambisome	Exitus
4	2	Female	2015	Metabolic disease	Blood	Yes	Fluconazole	Ambisome	Discharged
5	4	Female	2018	Immunodeficiency	Blood	None	Fluconazole	Caspofungin, Ambisome	Exitus
6	93	Male	2019	Sickle cell anemia	Blood	Yes	None	Ambisome, Caspofungin	Discharged
7	141	Male	2019	Immunodeficiency	Blood	Yes	Mikafungin	Fluconazole	Discharged
8	143	Male	2019	Immunodeficiency	Blood	Yes	None	Voriconazole	Discharged
9	2	Female	2020	Congenital heart disease	Peritoneal fluid	Yes	Fluconazole	Fluconazole	Exitus
10	8	Female	2021	Immunodeficiency	Blood	Yes	Fluconazole	Voriconazole Ambisome	Discharged
11	158	Male	2024	ALLa	Blood	None	Posaconazole	Posaconazole, Ambisome	Exitus
12	141	Male	2024	ALLa	Blood	Yes	Ambisome	Voriconazole, Ambisome	Discharged

^aAcute lymphocytic leukemia.

Underlying conditions and risk factors

All patients had underlying diseases. The distribution was as follows: Hematologic malignancy (n = 4, 33.3%), immunodeficiency (n = 4, 33.3%), congenital heart disease (n = 1, 8.3%), metabolic disease (n = 1, 8.3%), muscular dystrophy (n = 1, 8.3%), and sickle cell anemia (n = 1, 8.3%) (Table 2). Only one patient had received antifungal prophylaxis prior to the onset of infection.

Nine patients (75%) were receiving broad-spectrum antibiotics at the time of diagnosis. None of the patients were on parenteral nutrition. Eleven patients (91.7%) had a central venous catheter. Seven patients (58.3%) had a history of pediatric intensive care unit admission, with a median ICU stay of 28 days (range: 3–64 days). The median total hospital stay was 44 days (range: 16–76 days) (Table 1).

Hematological parameters

The median white blood cell count was 8.5 × 10³/μl (range: 1–33.4), median absolute neutrophil count 3.85 × 10³/μl (range: 1–28.7), median absolute lymphocyte count 1.3 × 10³/μl (range: 1–16.6), and median platelet count 102 × 10³/μl (range: 18–491). Four patients were neutropenic; 40% of the deceased patients were neutropenic.

Antifungal treatment and susceptibility

Prior to the detection of Trichosporon growth, nine patients received antifungal therapy based on clinical judgment. Of these, five were treated with fluconazole, and one each with liposomal amphotericin B (L-AmB), caspofungin, micafungin, and posaconazole.

Following identification of Trichosporon, antifungal therapy was adjusted. MIC values were determined for all isolates. Voriconazole had MIC <0.12 in eight patients (66.6%), while L-AmB had MIC <0.25 in only two patients (16.6%) (Table 3).

Table 3.

Minimum inhibitory concentrations (mg/ml) for Trichosporon isolates.

Case no	Fungal isolate	Amphotericin-B	Caspofungin	Fluconazole	Flucytosine	Micafungin	Voriconazole
1	Trichosporon spp.	2		32	16		≤0.12
2	Trichosporon Asahii	4		2	8
3	Trichosporon Asahii	1	≥4	2	8	>=4	≤0.12
4	Trichosporon Asahii	1	≤0.25	≤1	≤1	≤0.06	≤0.12
5	Trichosporon Asahii	0.5	≥8	2	≥64	>=8	≤0.12
6	Trichosporon Asahii	≤0.25	≥8	4	≤1	4	≤0.12
7	Trichosporon Asahii		≥8	2		≥8
8	Trichosporon mucoides	0.5	≥8	8	≥64	≥8	≤0.12
9	Trichosporon asahii	8	≥8	4	8	≥8	≤0.2
10	Trichosporon asahii	≤0.25	≥8	≤0.5	8	≥8	≤0.12
11	Trichosporon asahii		≥8	2		≥8
12	Trichosporon mucoides	0.5	≥8		≥64	≥8

Treatment regimens included voriconazole monotherapy (n = 2), voriconazole + L-AmB (n = 4), L-AmB + caspofungin (n = 2), fluconazole monotherapy (n = 2), L-AmB monotherapy (n = 1), and L-AmB + posaconazole (n = 1). Median treatment duration was 16 days (range: 7–30 days). One patient (Case 9) who died received fluconazole monotherapy, and therapy could not be changed due to rapid deterioration. Another patient (Case 7) also received fluconazole monotherapy and was later found to have recurrent Trichosporon growth during a subsequent hospitalization.

In one patient with hematologic malignancy (Case 11), despite appropriate antifungal therapy, catheter removal, and antifungal prophylaxis, a second episode occurred five months later during a period of profound neutropenia.

Clinical outcomes and mortality

Four of the five patients who died had received combination therapy. Of the seven survivors, three were discharged with antifungal prophylaxis.

The overall mortality rate was 41.7%. The 7-day mortality rate was 8.3%, and the 30-day mortality rate was 25%. Underlying conditions of deceased patients included hematologic malignancy (n = 2), congenital heart disease (n = 1), immunodeficiency (n = 1), and muscular dystrophy (n = 1).

Discussion

Trichosporon species are rare but increasingly recognized fungal pathogens that can cause invasive infections, particularly in immunocompromised individuals. These infections are associated with high morbidity and mortality, and their diagnosis and treatment remain challenging [11–13]. Trichosporon was first described in the 1890s and the first systemic infection related to Trichosporon was reported in 1970 [5, 14]. While Trichosporon species are part of the normal human flora and found in nature, under certain conditions (especially in immunosuppressed hosts) they can cause both superficial and life-threatening invasive infections [6].

Although exact prevalence rates vary by region and patient population, global estimates suggest that Trichosporon species account for 0.5–3.5% of all invasive fungal infections, with higher frequencies in immunocompromised patients [15]. In pediatric populations, available data remain limited. A multi-center study in Latin America identified Trichosporon as the causative agent in 1.1% of fungemia episodes in children with cancer, while lower but increasing detection rates have been reported in studies from Asia and Europe [16, 17]. Most studies in children involve small cohorts [15]. In this study, we present a decade-long experience with 12 pediatric cases of invasive Trichosporon infection at a single tertiary center, contributing valuable data to a sparsely populated field.

Consistent with previous studies, T. asahii was the most frequently isolated species in our cohort (75%), followed by T. mucoides (16.7%) [18]. This distribution is comparable to findings by Alboloshi et al. [19], who reported T. asahii in 90.5% and T. mucoides in 9.5% of pediatric cases. The predominance of T. asahii in bloodstream infections highlights its clinical relevance in pediatric settings.

Underlying comorbidities were present in all patients in our series. Hematologic malignancies (33.3%) and immunodeficiencies (33.3%) were the most common risk factors, in line with prior reports [20, 21]. Other less frequent underlying conditions included congenital heart disease, metabolic disease, muscular dystrophy, and sickle cell anemia. While malignancy is a well-established risk factor, our findings reinforce the importance of considering a broader spectrum of immunocompromising and chronic conditions [15, 22].

Regarding treatment options for invasive Trichosporon infections, L-AmB monotherapy was commonly used before the 2000s, and in the years following, triazoles were introduced as part of the treatment regimen [16]. Since 2014, European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Confederation of Medical Mycology (ECMM) guidelines have recommended voriconazole as the first-line treatment [23]. Studies have shown that L-AmB was effective in treating neonates, but particularly in patients with underlying hematologic diseases, the response to L-AmB was inadequate [6, 7]. It has been reported that L-AmB exhibits varying in vitro and in vivo activities against Trichosporon species, and resistance to the drug may develop over time [24].

In the study by Li et al. [25], which evaluated 140 patients with Trichosporon asahii infection, the effectiveness of L-AmB monotherapy was found to be 70.6%, while the effectiveness of triazoles as antifungal treatment was 74.1%. The combined use of L-AmB and triazoles showed an effectiveness of 57.9%. In the study by Kuo et al. [26], it was demonstrated that voriconazole treatment was more effective than other antifungal treatments in terms of survival. In our study, 12.5% of the patients received voriconazole monotherapy, while 37.5% were treated with a combination of voriconazole and another antifungal agent. The most common combination was L-AmB and voriconazole. Although this combination therapy was preferred on a case-by-case basis, no significant effectiveness against widespread Trichosporon infections was demonstrated [25]. Our findings support this observation.

Studies on the mortality rates of Trichosporon infections show varying results depending on the age group and center where the study was conducted. In the study by Alboloshi et al. [19], the mortality rate was 20% in patients under 10 years of age and 50% in those aged 10–65 years. In our study, similarly to the literature, the overall mortality rate was 41.7%. The 7-day mortality rate was 8.3%, and the 30-day mortality rate was 25%. Studies have shown that the choice of antifungal drugs used in treatment does not independently affect mortality, but factors such as the presence of neutropenia and immunodeficiency, the time of diagnosis, the presence of central venous catheters, and the appropriate timing and duration of antifungal therapy have been found to affect mortality [23]. In a multi-center study conducted in Turkey by Kara et al. [23], similar to our study, the mortality rate was 28.5%, and it was emphasized that underlying diseases affect prognosis and that further studies are needed for appropriate antifungal treatment. In our study, a patient with hematologic malignancy was treated with an appropriate duration of antifungal therapy, the existing central venous catheter was removed, and antifungal prophylaxis was administered, yet the patient developed Trichosporon again 5 months after the first infection during a period of deep neutropenia. Voriconazole and L-AmB combination therapy was started for this patient, but the patient, who also had accompanying neutropenia, died in a severe septic condition. In patients with worsening clinical conditions, neutropenia, and immunosuppression, Trichosporon species that remain colonized anywhere in the body can lead to active invasive infections again, thereby increasing mortality. When initiating empirical therapy, previous cultures should be screened for fungal growth, and the appropriate antifungal treatment should be started as soon as possible.

In our study, findings suggest that prolonged hospitalization, increased ICU stay, the use of multiple broad-spectrum antibiotics, and prolonged use of central venous catheters increase the risk of Trichosporon infections. However, no definitive statistical analysis has been conducted in this regard.

When invasive fungal infection is suspected, the antifungal agent to be used in treatment should be started empirically as soon as possible based on the current clinical flora, and treatment should continue with the most appropriate antifungal agent based on culture, antibiogram results, and MIC values.

The limitations of our study include the identification of invasive Trichosporon infection in only 12 patients during a 10-year period at a single center. This resulted in statistical data being obtained from a limited number of patients, and thus the results could not be generalized statistically. Upon reviewing the literature, it has been observed that existing studies on invasive Trichosporon infections are limited, and many studies have been case reports. The purpose of this study is to highlight Trichosporon species, a rare fungus found in our normal microbial flora, which can cause invasive diseases in conditions such as neutropenia and immunodeficiency, and contribute to the literature in this regard. Thus, our study aims to raise awareness about this clinically important fungus due to its rarity.

Conclusion

Invasive Trichosporon infections can lead to significant clinical outcomes with high morbidity and mortality rates. Early diagnosis and an appropriate treatment approach play a critical role in improving the quality of life and reducing the risk of mortality. However, more research is needed to determine the appropriate therapeutic agents for the effective management of these infections. Developing early diagnostic methods and antifungal treatment protocols is crucial for improving the treatment success of Trichosporon infections.

Author contributions

Asena Ünal (Conceptualization [lead], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [lead], Methodology [lead], Project administration [lead], Resources [equal], Software [equal], Supervision [equal], Validation [equal], Visualization [equal], Writing—original draft [lead], Writing—review & editing [lead]), Emel Bakanoglu (Conceptualization [equal], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [equal], Methodology [equal], Project administration [equal], Resources [equal], Software [equal], Supervision [equal], Validation [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), Fatma Tugba Çetin (Conceptualization [equal], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [equal], Methodology [equal], Project administration [equal], Resources [equal], Software [equal], Supervision [equal], Validation [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), Gökçe Oguz (Conceptualization [equal], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [equal], Methodology [equal], Project administration [equal], Resources [equal], Software [equal], Supervision [equal], Validation [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), Ümmühan Çay (Conceptualization [lead], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [equal], Methodology [lead], Project administration [lead], Resources [equal], Software [equal], Supervision [lead], Validation [equal], Visualization [equal], Writing—original draft [lead], Writing—review & editing [lead]), Özlem Özgür Gündeslioglu (Conceptualization [lead], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [equal], Methodology [supporting], Project administration [lead], Resources [equal], Software [equal], Supervision [lead], Validation [equal], Visualization [equal], Writing—original draft [lead], Writing—review & editing [lead]), Filiz Kibar (Conceptualization [equal], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [equal], Methodology [equal], Project administration [equal], Resources [equal], Software [equal], Supervision [equal], Validation [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), and Derya Alabaz (Conceptualization [lead], Data curation [equal], Formal analysis [equal], Funding acquisition [equal], Investigation [equal], Methodology [lead], Project administration [equal], Resources [equal], Software [equal], Supervision [equal], Validation [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal])

Conflict of interest: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, or publication of this article.

Ethical approval

The study was granted ethical approval by the Çukurova University Ethics Committee (Meeting number: 151, 03 January 2025).