Trichosporon fungemia in critically ill patients: A case series

ABSTRACT

Trichosporon species are emerging opportunistic pathogens capable of causing a spectrum of disease, from superficial skin infections to deep-seated, disseminated, and life-threatening infections. These infections are often challenging to diagnose due to their rarity, frequent misidentification as Candida, and intrinsic resistance to conventional antifungal therapies, resulting in delays in appropriate management. We report a case series of Trichosporon fungemia in six critically ill patients, highlighting varied clinical presentations. Common comorbidities included diabetes mellitus, hypertension, anemia, hypothyroidism, sepsis, multiorgan dysfunction, and complications related to indwelling devices. All cases had blood culture–confirmed Trichosporon fungemia. The overall mortality was 66.7% (4/6 cases). Our findings emphasize the importance of early recognition, prompt antifungal therapy, and strict infection control measures to improve outcomes in high-risk patients.

Introduction

Trichosporon species (spp.) are emerging opportunistic pathogens capable of causing a spectrum of disease, ranging from superficial skin infections to deep-seated, disseminated, and life-threatening infections, with mortality rates approaching 80%, particularly among immunocompromised individuals.[1] Trichosporon spp. were first described in 1865 by Beigel as the etiological agent of white piedra. However, their clinical significance as invasive pathogens became evident in 1970, when the first case of cerebral trichosporonosis was reported.[2,3] In many settings, diagnosis of Trichosporon relies primarily on morphological examinations, which can lead to misdiagnosis/delayed identification. Due to their rarity, misdiagnosis with Candida/Geotrichium, and resistance to conventional antifungal treatments, these infections are often challenging to diagnose further leading to delay in initiation of anti-fungal therapy.[1]

This prospective case series was conducted over 12.08.2024 to 31.12.2025 and included patients with blood culture–confirmed Trichosporon fungemia. Clinical and laboratory data were retrieved from medical records, and a total of six cases were analyzed. This case series aims to describe the clinical presentation, predisposing factors, diagnostic findings, treatment approaches, and outcomes of Trichosporon fungemia in critically ill patients.

Case Series

Case 1

A 62-year-old male presented in emergency with acute pain abdomen, gradually progressing, diffuse, dull-aching, nonradiating, cramping, and localized to epigastric and umbilical regions, and relieved on medication for 15 days. There was nonbilious, non-blood-stained vomiting (one-to-two tablespoon/episode) with partially digested food and 3–4 episodes/day of maroon-colored rectal bleeding with clots, characterized by a jet of blood not mixed with stool over the past 2 days. History was notable for chronic kidney disease on hemodialysis (1.5 years), with diabetes mellitus and hypertension (2 months). He had a previous right femur fracture with in-situ implant placed 5 years ago.

On examination, he was febrile (101.6°F), tachycardic (140 bpm), hypotensive (83/62 mmHg), and tachypneic (24/min) with SpO2-98% on room air. The patient was provisionally diagnosed with sepsis, and routine investigations were sent prior to initiation of empirical therapy. Intravenous antibiotic therapy was started with piperacillin/tazobactam (4.5 gm loading dose, followed by 2.25 gm every 8 hours) along with metronidazole (100 ml every 8 hours). After stabilization, the patient was transferred to the intensive care unit. Complete blood examination revealed leukocytosis (43.5 × 10³/µL), anemia (hemoglobulin 3.8 g/dl), thrombocytopenia (87,000/µl), low hematocrit (26.3%), and elevated red cell distribution width–coefficient of variation (20%). Liver function tests showed low direct bilirubin (0.9 mg/dl), hypoproteinemia (5.5 mg/dl), and low albumin/globulin ratio (0.7:1). Total iron binding capacity levels were decreased (159 µg/dl). Renal function tests demonstrated elevated s.creatinine (5.4 mg/dl), uric acid (9.3 mg/dl), and urea (141.2 mg/dl). Serum electrolytes were deranged, with hypernatremia (155 mmol/l), hyperchloremia (108 mmol/l), and hypokalemia (2.9 mmol/l). Inflammatory markers were raised [the procalcitonin and erythrocyte sedimentation rate (ESR) were 62.9 ng/ml, 22 mm/hr, respectively]. Given the severity of derangements, treatment was escalated with vasopressors and hemodialysis. Thyroid function tests revealed elevated thyroid stimulating hormone (TSH 14.56 µIU/ml) with low T3 (0.58 ng/dl) and T4 (3.85 µg/dl) levels. Accordingly, the patient was started on oral thyroxine 25 µg-once-daily dose.

After admission, the patient had one episode of seizure and managed successfully with Inj levetiracetam (500 mg every 8 hourly). Routine urine examination revealed leukocytosis, hematuria, and proteinuria, while urine culture was inconclusive. Ultrasound abdomen demonstrated cystitis, prostate enlargement, a simple cortical cyst in the left kidney, and mild bilateral renal echogenicity with partial loss of contour. Based on these findings, treatment was escalated to oral nitrofurantoin (100 mg every 12 hourly). While X-ray abdomen showed multiple dilated bowel loop, upper gastrointestinal endoscopy showed pangastritis. But the patient keeps on deteriorating, so further investigations were done. Chest-X-ray showed discrete patchy opacities in the right lower lobe and bilateral hilar region, and two-dimensional echocardiography revealed 40% left ventricular ejection fraction with left ventricular diastolic dysfunction grade I, trivial mitral regurgitation, and mild pulmonary arterial hypertension. The blood culture was beeped positive after 48 hours of incubation, and direct Gram staining showed the presence of Gram-positive arthroconidia and fungal hyphae, and the clinician was critically alerted. On sheep blood agar, grayish-white dry, powdery irregularly wrinkled colonies with a heaped-up center were obtained. On lactose cotton blue preparation, many hyaline septate hyphae with blastoconidia singly/short chains and abundant arthroconidia were identified as Trichosporon spp., and urease test was positive [Figure 1]. Final confirmation of fungemia was obtained using a Vitek-2 Compact system, which identified Trichosporon inkin. Unfortunately, the patient expired from sepsis, septic shock, and multiorgan failure before antifungal therapy could be initiated.

Figure 1.

Phenotypic and biochemical characteristics of Trichosporon species: (a) – Gram-stained smear prepared from direct positive blood culture showing hyphae (i) with blastoconidia (ii) and arthroconidia (iii) [Magnification-1000x]. (b) - Sheep blood agar plate showing dry, grayish-white, wrinkled colonies. (c) - Positive Christensen’s urease test following incubation at 35^OC for 24 hrs. (d) - Gram-stained smear from colony showing hyphae (i) along with blastoconidia (ii) and arthroconidia (iii) [Magnification-1000x]. (e) - Lactose cotton blue preparation showing hyphae (i) along with blastoconidia (ii) and arthroconidia (iii) [Magnification-400x]. Black arrows/arrowheads indicate hyphae (i), blastoconidia (ii), and arthroconidia (iii) in the respective panels

Case 2

A 57-year-old male presented with fever, chest pain, shortness of breath, and multiple fluid-filled vesicles over the lips for 5 days. On examination, he was febrile (101°F), hypertensive (182/106 mmHg), tachypneic (22/min), and maintaining SpO₂ of 98% on room air. The patient was admitted for further evaluation, and routine laboratory investigations were sent. Empirical intravenous antibiotic therapy with meropenem was initiated (500 mg every 8 hourly).

Laboratory investigations revealed leukocytosis (15.66 × 10³/µl), anemia (hemoglobin 8.2 gm/dl), and lymphocytopenia (11.4%). Liver function tests showed elevated alkaline phosphatase and lipase levels (210.6 U/l and 267.2 U/l, respectively). Renal function tests indicated raised urea, creatinine, and uric acid levels (192.4 mg/dl, 8.9 mg/dl, and 9 mg/dl, respectively). Serum electrolytes demonstrated hyponatremia with mild derangements in potassium, chloride, and bicarbonate levels (133 mmol/l, 4.89 mmol/l, 96.6 mmol/l, and 17.7 mmol/l, respectively). Thyroid profile revealed elevated TSH (16.56 µIU/ml) with low T3 (0.68 ng/dl) and T4 (3.05 µg/dl), and the patient was started on oral thyroxine 25 µg once daily. Parathyroid hormone was elevated (113 pg/mL), and inflammatory markers were raised (ESR 89 mm/hr).

Blood culture grew Trichosporon mucoides, and the patient was diagnosed with chronic kidney disease, hypothyroidism, catheter-related bloodstream infection, and herpes labialis. Treatment was escalated to acyclovir (400 mg orally three times daily), fusidic acid cream twice daily, and combination antifungal therapy with intravenous voriconazole (80 mg twice daily) and liposomal amphotericin B (16 mg daily), with monitoring of voriconazole levels twice weekly. The patient showed good clinical response, with marked improvement noted at 1-month follow-up.

Case 3

A 27-year-old male presented with fever and chest pain for 5 days. He was a known case of hypertension, type 2 diabetes mellitus, and renal transplant failure. The patient was admitted for further evaluation and was found to have bilateral pleural effusion with pericardial effusion. Laboratory investigations revealed leukocytosis (18.94 × 10³/µl), neutrophilia (94.9%), and severe anemia (hemoglobin 5.3 gm/dl), along with elevated inflammatory markers (ESR 27 mm/hr, C-reactive protein 90 mg/l). Empirical intravenous meropenem therapy was initiated (500 mg every 8 hourly). Blood culture subsequently grew Trichosporon asahii, and treatment was escalated to voriconazole (a loading dose of 300 mg every 12 hourly, followed by a maintenance dose of 200 mg every 12 hourly). The patient showed clinical improvement, and follow-up after 1 month revealed significant improvement in laboratory parameters.

Case 4

A 29-year-old female presented with 80–85% superficial to deep thickness burns. Laboratory investigations revealed leukocytosis (30.96 × 10³/µL), neutrophilia (83.6%), lymphopenia (7.3%), and deranged serum electrolytes, including hyponatremia (124 mmol/l), hypomagnesemia (1.4 mg/dl), and hyperphosphatemia (5.5 mg/dl). Arterial blood gas (ABG) analysis revealed acidemia with reduced pH, PaCO₂, and bicarbonate levels (7.25, 28 mmHg, and 12 mEq/l, respectively), suggestive of mixed respiratory and metabolic derangement. Pus culture grew Pseudomonas aeruginosa, and antibiotic therapy was escalated to piperacillin/tazobactam (4.5 gm 8 hourly). Blood culture subsequently revealed growth of Trichosporon asahii. The patient developed acute respiratory distress syndrome, metabolic acidosis, and septic shock. Despite supportive management, the patient expired before initiation of antifungal therapy.

Case 5

A 59-year-old male presented with sudden onset of right-sided weakness, altered sensorium, and aphasia. This was preceded by abnormal movements of the left lower limb, followed by upward rolling of the eyes and unresponsiveness to commands. There was no history of tongue bite, urinary incontinence, loss of vision, or loss of smell. He was a known case of type 2 diabetes mellitus, hypertension, chronic kidney disease, coronary artery disease, and status post percutaneous transluminal coronary angioplasty.

On examination, the patient was afebrile with a heart rate of 79/min and a blood pressure of 130/80 mmHg. Glasgow Coma Scale was E2V1M2. The patient was intubated. His NCCT brain revealed reduced caliber of the middle cerebral artery, and the patient underwent emergency mechanical thrombectomy along with left frontotemporoparietal decompressive craniectomy and tracheostomy.

Laboratory investigations showed leukocytosis (15.6 × 10³/µl) and normocytic normochromic anemia with anisocytosis. Two units of packed red blood cells were transfused. Renal function tests showed elevated blood urea (100.2 mg/dl) and creatinine (3.5 mg/dl), with hyponatremia (126 mmol/l) and elevated LDH (315.4 U/l). Hemodialysis was initiated.

On blood culture, mixed growth of Acinetobacter baumannii complex and Trichosporon asahii was obtained. While on endotracheal aspirate culture and urine culture, growth of Klebsiella pneumoniae and Enterococcus faecalis was obtained, respectively. Despite aggressive management, the patient developed severe sepsis and expired.

Case 6

This patient had a similar clinical presentation to Case 2. She presented with fever, shortness of breath, and drowsiness. On examination, she was febrile (102°F), tachypneic (24/min), and tachycardic (150/min) and had SpO₂ of 95% on room air. ABG analysis showed acidemia with elevated PaCO₂ and relatively normal bicarbonate levels (pH 7.22, PaCO₂ 70 mmHg, and HCO₃⁻ 26 mEq/l), suggestive of respiratory acidosis with partial metabolic compensation. On blood culture, growth of Trichosporon asahii was obtained. She was diagnosed with type 2 respiratory failure, lower respiratory tract infection, diffuse encephalopathy, sepsis, and septic shock. Despite management, the patient expired.

The detailed clinical and laboratory characteristics of all cases are presented in Table 1.

Table 1.

Clinical and laboratory characteristics of patients with trichosporon fungemia

Patient details	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6
Age	62	57	27	29	59	65
Sex	Male	Male	Male	Female	Male	Male
Presenting complaints	Pain abdomen, vomiting, and bleeding per rectal	Fever and chest pain, shortness of breath and pain abdomen from last 5 days	Fever, chest pain	80-85% superficial to deep thickness Burns	Right-sided weakness, altered sensorium and aphasia	Fever, shortness of breath and drowsiness.
Underlying medical condition	Chronic kidney disease, sepsis, hypothyroidism, anemia and Hypertension	Chronic kidney disease, hypertension, anemia of chronic disease, hypothyroidism, and herpes labialis	Hypertension, diabetes mellitus Type II, and renal transplant failure	Acute respiratory distress syndrome, septic shock, metabolic acidosis	Diabetes mellitus Type II, hypertension, chronic kidney disease, coronary artery disease and post percutaneous transluminal coronary angioplasty, acute ischemic stroke, iron deficiency anemia, and electrolyte imbalance	Type 2 respiratory failure, lower respiratory tract infection, diffuse encephalopathy, sepsis, septic shock
Neutropenia	No	No	No	No	No	No
Disseminated	No	No	Yes	Yes	Yes	Yes
Co-infection	UTI (culture negative), bloodstream infection (Trichosporon inkin)	Herpes labialis, multiorgan failure, bloodstream infection (Trichosporon mucoides)	Bilateral pleural effusion, Pericardial effusion, bloodstream infection (Trichosporon asahii)	Bloodstream infection (Trichosporon asahii), Pus culture (Pseudomonas aeruginosa)	Sepsis, blood culture (Acinetobacter baumannii complex and Trichosporon asahii), endotracheal aspirate culture (Klebsiella pneumoniae), urine culture (Enterococcus faecalis).	Bloodstream infection (Trichosporon asahii)
Prior use of antibiotics within 30 days	Yes	Yes	Yes	No	Yes	Yes
Prior use of corticosteroids	Yes	Yes	Yes	No	Yes	Yes
Presumed source of infection	Central venous catheter	Central venous catheter	Respiratory route	Central venous catheter, debridement site	Central venous catheter, pneumonia	Respiratory route or catheter-related
Antifungal therapy given	No	Yes	Yes	No	No	No
Recurrence	Not applicable	No	No	Not applicable	No	Not applicable
30 days Outcome	Expired	Survived	Survived	Expired	Expired	Expired

Discussion

Trichosporon spp. are widely distributed in nature and may colonize the skin, oral cavity, respiratory tract, gastrointestinal tract, and vagina. Differentiating colonization from true invasive infection is crucial as mucosal translocation can lead to fungemia and systemic dissemination, as observed in Cases 3–6. Although catheter-associated bloodstream infections without overt organ involvement are increasingly being reported, this may suggest a changing epidemiological and pathogenic pattern.[2,4]

Conventional diagnostic methods, including culture and histopathology, have suboptimal sensitivity and often detect infection at advanced stages when fungal burden is high, potentially delaying targeted therapy and worsening outcomes. This has led to increasing interest in rapid molecular and serological diagnostic tools for earlier detection.[5] Automated identification systems such as VITEK, as used in our cases, may also aid in the identification of Trichosporon spp.[6]

In the present case series, Trichosporon fungemia was observed predominantly in patients with significant comorbidities, including diabetes mellitus, chronic kidney disease, and prolonged hospitalization with exposure to broad-spectrum antibiotics and indwelling devices. These factors likely contribute to host immune dysregulation and disruption of normal microbial flora, predisposing to invasive fungal infection. Notably, neutropenia was not observed in any of the patients, suggesting that Trichosporon infection is not restricted to classical neutropenic or hematological malignancy populations and may also occur in critically ill medical and surgical patients. Repeat fungal cultures (Cases 2 and 3), when performed during follow-up, were negative, supporting microbiological resolution in those patients.

The clinical presentation in our series was nonspecific, with fever, respiratory distress, altered sensorium, and features of sepsis being the most common manifestations. This overlaps significantly with bacterial sepsis, making early clinical suspicion challenging. Similar diagnostic difficulties have been reported in previous studies, where delayed recognition contributed to poor outcomes. Prognosis largely depends on host immune status and clinical condition, with better outcomes reported in patients without persistent neutropenia or irreversible organ dysfunction.[7,8]

A key finding in our series was the high mortality rate (66.7%), consistent with previously reported literature describing Trichosporon fungemia as an aggressive infection with poor prognosis, particularly in intensive care unit settings. Outcome variability among patients appears to be multifactorial. Survival in some cases despite co-infections may be attributed to earlier diagnosis, lower organ dysfunction at presentation, and timely escalation of antifungal therapy. In contrast, patients presenting with septic shock, multiorgan failure, or delayed initiation of appropriate antifungal treatment had poor outcomes.

Antifungal management remains challenging due to the intrinsic resistance of Trichosporon spp. to echinocandins and reduced susceptibility to amphotericin B.[9] Voriconazole is considered the most effective antifungal agent for Trichosporon fungemia and has been associated with improved survival compared with amphotericin B-based regimens. Large case series and reviews support better outcomes with triazole therapy, whereas echinocandins demonstrate negligible activity against Trichosporon species.[10,11,12] However, the lack of routine antifungal susceptibility testing further limits targeted therapy. In our series, antifungal treatment was initiated or escalated only after blood culture identification, underscoring the importance of rapid microbiological diagnosis in guiding timely and appropriate therapy.

Another important observation was the occurrence of mixed bacterial and fungal bloodstream infections in some critically ill patients, suggesting severe immune dysfunction and extensive nosocomial exposure, further complicating management and contributing to poor outcomes. In addition, prior exposure to broad-spectrum antibiotics and corticosteroids in several patients may have further predisposed to fungal proliferation by disrupting normal host microbiota and inducing transient immunosuppression.

This case series emphasizes that Trichosporon fungemia should be considered in critically ill patients with persistent sepsis, particularly in those with indwelling devices and prior broad-spectrum antibiotic exposure, even in the absence of hematological malignancy or neutropenia. The main contribution of this case series lies in highlighting real-world diagnostic and therapeutic challenges in Trichosporon fungemia in critically ill patients, particularly the variability in outcomes despite similar comorbid profiles and co-infections, as well as limitations in antifungal susceptibility-guided therapy in routine clinical practice.

Emerging molecular diagnostic approaches, including next-generation sequencing (NGS) and third-generation sequencing (TGS), offer the potential for rapid and comprehensive pathogen detection directly from clinical specimens. These technologies may enable earlier identification of Trichosporon species, facilitate timely initiation of appropriate antifungal therapy, and improve clinical outcomes, particularly in patients with severe or immunocompromised conditions. However, further studies are required to establish their clinical utility, standardization, and cost-effectiveness in routine practice.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.