| Abstract|| |
Trichosporon asahii (formerly known as Trichosporon beigelii) is an emerging, life-threatening opportunistic pathogen and has been found to be invariably associated with disseminated or deep-seated trichosporonosis, more so among the patients with granulocytopenia or hematological malignancies. We here report a successfully treated case of disseminated trichosporonosis in a known diabetic, 14-year-old girl, admitted to our hospital with chief complaints of fever, chills, and burning micturition since 3 weeks. Disseminated trichosporonosis is usually an insidious disease with poor prognosis. Early diagnosis is crucial for successful treatment. High index of clinical suspicion and extensive microbiological investigations can clinch the diagnosis.
Keywords: Amphotericin B, fluconazole, fungemia, trichosporonosis
|How to cite this article:|
Negi V, Sharma M, Juyal D, Kotian S, Sharma N. Disseminated trichosporonosis due to Trichosporon asahii in a diabetic patient. Indian J Pathol Microbiol 2015;58:246-8
|How to cite this URL:|
Negi V, Sharma M, Juyal D, Kotian S, Sharma N. Disseminated trichosporonosis due to Trichosporon asahii in a diabetic patient. Indian J Pathol Microbiol [serial online] 2015 [cited 2020 Feb 19];58:246-8. Available from: http://www.ijpmonline.org/text.asp?2015/58/2/246/155333
| Introduction|| |
The basidiomycetous yeast, Trichosporon Behrend, is a medically important genus with distinct morphological characters of budding cells and true mycelium that disarticulate to form arthroconidia.  The fungus commonly inhabits the soil and other environmental sources and in humans can transiently colonize skin, mucosal surfaces, respiratory and gastrointestinal tract. , In the past, a sole species Trichosporon beigelii was correlated to human pathology but recently, the genus Trichosporon has gone an extensive taxonomic re-evaluation and T. beigelii has been divided into a number of distinct species.  The various species that are now recognized as pathogenic to humans are Trichosporon asahii, Trichosporon asteroides, Trichosporon domesticum, Trichosporon cutaneum, Trichosporon inkin, Trichosporon mucoides, Trichosporon ovoides, Trichosporon loubieri, Trichosporon pullulans, and Trichosporon japonicum. 
Trichosporon species can cause a disseminated invasive infection known as trichosporonosis. Disseminated trichosporonosis is an uncommon but increasingly reported and frequently fatal mycosis in immunocompromised patients.  T. asahii has been found to be invariably associated with disseminated or deep-seated trichosporonosis, more so among the patients with granulocytopenia or hematological malignancies.  It is believed that most cases of trichosporonosis attributed previously to T. beigelii and T. cutaneum were probably caused by T. asahii, an emerging, life-threatening, opportunistic systemic pathogen.  We here report a successfully treated case of disseminated trichosporonosis due to T. asahii in a diabetic girl. Although cases of disseminated trichosporonosis have been reported from various parts of the India ,, but none is reported from Uttarakhand state and probably this is the first case to be reported from this part of the country.
| Case Report|| |
A 14-year-old girl was admitted to the medicine department of our hospital with chief complaints of fever, chills, and burning micturition since 3 weeks. She took prescription from an unauthorized local medical practitioner in the village and had cotrimoxazole (40 mg/200 mg q12h) and ciprofloxacin (250 mg q12h) for 1-week, but symptoms still persisted. As per her previous medical records, she had type I diabetes mellitus (DM) with poor drug compliance. On physical examination, she was found to be severely ill, anemic, and was febrile (102°F). She was underweight for her age and belonged to socioeconomically poor status.
Laboratory investigations revealed hemoglobin 7.4 g/dl, total leukocyte count 16,000 cells/μl (81% neutrophils, 13% lymphocytes, 5% monocytes, and 1% eosinophils), erythrocyte sedimentation rate 65 mm/1 st h, and a positive C-reactive protein (230 mg/L). Random blood sugar was 430 mg/dl.
Renal function tests were slightly impaired with serum creatinine 2.4 mg/dl, blood urea nitrogen 29 mg/dl and uric acid 6.3 mg/dl. On urinalysis, albuminuria (+) was detected. A full sepsis profile was requested and patient was started empirically on intravenous (IV) amikacin (7.5 mg/kg q12h), ceftazidime (50 mg/kg q8h), and vancomycin (20 mg/kg q8h).
Microscopic examination of the urine revealed presence of pus cells and budding yeast cells [Figure 1]a. The sample was inoculated on 5% sheep blood agar (BA), and MacConkey agar (MA), and plates were incubated at 37°C. After overnight incubation, a significant growth of tiny, creamy white, dry wrinkled colonies with irregular margins was grown on BA. Gram-stained smear of the colony showed septate hyphae with arthroconidia and budding yeast cells [Figure 1]b. The colonies were subcultured on sabouraud dextrose agar (SDA) and incubated at 37°C, which also yielded similar colonies within 24 h [Figure 2]. Two blood samples collected from different anatomical sites at the time of admission were also flagged positive after 12 h by BD Bactec 9120 (Becton Dickinson, USA). A subculture from the blood culture bottle was done on BA and MA, which after overnight incubation showed the similar growth as of urine culture and the Gram stain morphology of the colonies was also same. A provisional diagnosis of yeast-like fungi was intimated to the physician for prompt institution of antifungal therapy, and IV fluconazole (200 mg q24h) was added to the regime. Two more early morning samples of urine and a repeat blood sample were analyzed which showed similar findings.
|Figure 2: Growth of Trichosporon asahii on sabouraud dextrose agar showing dry wrinkled colonies with irregular margins|
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Based on corn meal agar morphology, urease activity, growth on SDA at 37°C and 42°C but not at 45°C, resistance to cycloheximide (0.01 mg/l) and carbohydrate assimilation profiles, the isolate from urine and blood was identified as T. asahii. The isolate was sent to PGIMER, Chandigarh for molecular typing where it was confirmed to be T. asahii by sequencing of the internal transcribed spacer (ITS) locus of the rDNA, using primers ITS1/ITS4 (ITS1: 5′-TCCGTAGGTGAACCTGCGG-3′; ITS4: 5′-TCCTCCGCT TAT-TGATATGC-3′). The sequence data were submitted for BLAST analysis at the NCBI site (http://www.blast.ncbi.nlm.nih.gov/blast). The Gene Bank database showed 99% identity with the T. asahii. The in vitro antifungal susceptibility of the isolate to amphotericin B, fluconazole, voriconazole, and itraconazole was determined by E-test system (AB Biodisk, Solna, Sweden) as per the manufacturer's instructions. The isolate was found sensitive to amphotericin B (MIC 0.25 μg/ml), fluconazole (2 μg/ml), and voriconazole (0.023 μg/ml), but was resistant to itraconazole (3 μg/ml).
During all this time despite the continued use of broad spectrum antibiotics and fluconazole the general condition of the patient did not improve. She persistently showed signs of sepsis, her fever spiked to 103.6°F, and she developed hematuria. On day 6 of her admission, liposomal amphotericin B was added to the regime. After 4 days of therapy, patient showed remarkable recovery and her temperature came down to 98.7°F. After 3 weeks of antifungal therapy, her urine and blood samples were sent for repeat fungal culture and were found to be negative.
| Discussion|| |
Disseminated trichosporonosis is a severe opportunistic mycosis and despite the antifungal therapy is associated with high mortality, with an overall mortality rate of up to 56.1%.  Clinically, trichosporonosis appears with fever, pulmonary infiltrates, azotemia, renal dysfunction, and skin lesions. The lack of clear and specific indications for the clinical interpretation of this disease is still a problem for clinicians. High index of clinical suspicion, timely diagnosis, and appropriate therapy determines the survival of the patient.
Our patient had manifestations of sepsis and urinary tract infection not responding to broad spectrum antibiotics which were later diagnosed as disseminated trichosporonosis. Timely detection of the organism and institution of appropriate therapy showed a positive outcome. The etiological role of T. asahii in this case was unequivocally established by repeated isolation of the fungus from two blood and three urine samples. Furthermore, the fact that following antifungal therapy, there was clearance of the organism from blood and urinary tract strongly associates T. asahii as a causative agent in this case. Recovery of the organism from blood and urine are the important indicators of dissemination of the organism.  T. asahii has extensively been recognized as an emergent agent of fungal invasive infections worldwide. ,,,,,, Our patient exhibited several risk factors (broad spectrum antibiotics, anemia, and DM with poor drug compliance) which may have contributed to acquisition and progression of infection. Moreover, she was underweight for her age and belonged to a socioeconomically low status. DM is recognized as an important risk factor for developing invasive trichosporonosis and could be a major contributory factor in this case.
Early treatment effectively reduces fungal dissemination, but resistance to Trichosporon species to many common antifungal agents has been encountered and remains a major challenge to patient management.  In vitro resistance to amphotericin B and a lesser extent, the azoles have been demonstrated.  However, the newer triazoles (voriconazole, posaconazole, ravuconazole) have shown good activity in vitro and are recommended for disseminated trichosporonosis.  Importantly, when there is clear evidence of fungal dissemination, a considered approach to antifungal intervention is paramount. In the present case, although the isolate was sensitive to fluconazole, the patient seemed not to respond to the fluconazole therapy. However, combination therapy with both fluconazole and amphotericin B yielded better response and patient showed remarkable recovery.
Disseminated trichosporonosis is usually an insidious disease but can present as an opportunistic infection in susceptible hosts, and the prognosis is quite poor. Early diagnosis is crucial for successful treatment. However, the diagnosis is likely to be missed due to the general lack of awareness about Trichosporon species as an unusual etiological agent in disseminated fungal infections. High index of clinical suspicion and extensive microbiological investigations can clinch the diagnosis.
| Acknowledgment|| |
We acknowledge the help extended by Dr. Arunaloke Chakrabarti, Professor and Head Department of Medical Microbiology, PGIMER, Chandigarh, for the species' identification and confirmation of the fungal isolate.
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Department of Microbiology and Immunology, Veer Chandra Singh Garhwali Government Medical Sciences and Research Institute, Srinagar Garhwal - 246 174, Uttarakhand
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]