Title: Complicated Trichosporon asahii Fungemia in an Unusual Host
Submitted by: Matthew Stack, MD; Luis Ostrosky-Zeichner, MD
Institution: UT Health Houston
Date Submitted: 10/9/2023
The patient is a 44 year old male with a past medical history most notable for kidney transplant done in 3/2020 (transplant was done outside our system) for ESRD secondary to HTN and type II diabetes. Patient’s other medical comorbidities were numerous and included atrial fibrillation, HFpEF, severe rheumatic mitral valve stenosis, pulmonary hypertension (on 2 liters of oxygen at home), peripheral arterial disease, type II diabetes, suspected cirrhosis, and obesity (s/p gastric sleeve). The patient’s post-transplant course was complex and was most recently (starting in Spring of 2023) complicated by Tandem heart placement for worsening heart failure, bioprosthetic mitral valve replacement, PEA cardiac arrest (requiring about 5 days of VA-ECMO), AKI needing CRRT, placement of tracheostomy, and pulmonary Mycobacterium abscessus infection. The patient was started on Tigecycline, Imipenem, and inhaled Amikacin for the pulmonary Mycobacterium abscessus, based on susceptibilities. The patient was ultimately discharged to a LTAC with a central venous catheter and was residing at the LTACH for about a month before he was readmitted to our facility for acute on chronic hypoxic respiratory failure and septic shock.
Upon admission, he was found to have both COVID-19 pneumonia and Stenotrophomonas maltophilia pneumonia. The patient was treated for COVID-19 with Dexamethasone and Remdesivir and was given 7 days of Levofloxacin for Stenotrophomonas maltophilia pneumonia. Patient was otherwise continued on his regimen for the pulmonary Mycobacterium abscessus. Bronchoscopy done on admission was positive for both CMV and HSV-1 PCR from the BAL fluid; it was unclear if this represented true pneumonitis vs asymptomatic shedding given patient’s acute illness and prolonged ICU stay. However, given the overall acuity of the patient’s situation, decision was made to treat as CMV/HSV-1 pneumonitis with a course of Valganciclovir induction therapy, followed by secondary prophylaxis. Patient did initially improve with the above-mentioned treatment, along with supportive ICU care.
However, about 10 days into the admission, he started to experience a clinical decline with increasing pressor requirements and worsening encephalopathy. Also of note, a serum B-d-glucan was obtained on admission (as part of a broad infectious workup) that came back somewhat elevated at 111 pg/mL. Given the patient’s clinical decline, elevated B-d-glucan, prolonged ICU stay, and presence of multiple central lines (one of which had been in place since previous admission about one month ago), there was concern for possible fungemia, so the Infectious Disease (ID) consult team recommended repeat blood cultures and initiation of empiric Micafungin therapy. As the ID consult team suspected, the patient’s blood cultures did grow a yeast (identification was still pending at about 72 hours). However, despite empiric Micafungin therapy, the patient’s overall clinical condition did not improve much. Existing central lines were removed/exchanged.
Vital signs: Temperature: 37.8°C; BP: 95/65 mmHg; pulse: 95/min; RR: 18/min
General: Chronically ill-appearing male
HEENT: Pupils equal, no scleral icterus, no sinus tenderness, no oral lesions
Neck: Supple, chronic trach in place.
Cardiovascular: Tachycardic. Normal S1 and S2
Respiratory: Scattered coarse breath sounds heard bilaterally; on ventilator support via trach
Gastrointestinal: Bowel sounds present, nontender, nondistended, soft, no masses
Extremities: 1+ pitting edema of bilateral lower extremities
Skin: Right upper extremity PICC line and right femoral tunneled dialysis catheter site without any associated surrounding redness, tenderness, or swelling but dressing on the right femoral tunneled dialysis catheter line looked old and did not appear to have been changed in the last several weeks
Neurologic: Alert and oriented but with waxing and waning mentation
Psych: Waxing and waning mentation; did not appear agitated
– White Blood Count: 6.5
– Hemoglobin: 7.6
– Hematocrit: 23.2
– Platelets: 17
– Creatinine: 1.05
– BUN: 79
– ALT: 25
– AST: 45
– Alkaline phosphatase: 374
– LDH: 267
– Serum galactomannan: 0.854 (reference range: less than 0.5)
– BAL galactomannan: 0.163 (reference range: less than 0.5)
– Repeat serum B-d-glucan: 127 pg/mL
– Urine histoplasma antigen: Negative
– Serum cryptococcal antigen: Negative
– Serum coccidioides serology: Negative
Question 1: What are probable/possible diagnoses?
Microbiology/Diagnostic Tests Performed:
– Repeat blood cultures; cultures were growing a yet-to-be identified yeast at 48 to 72 hours
– Repeat serum B-d-glucan: 127 pg/mL
– Repeat transthoracic echocardiogram: Did not show any evidence of vegetations
Possible diagnosis: Invasive candidiasis refractory to echinocandins or non-Candida yeast fungemia, resistant to echinocandins
– Trichosporon asahii fungemia/possible Trichosporon asahii endocarditis
– Trichosporon asahii MICs:
– Fluconazole: 1
– Voriconazole: 0.47
– Posaconazole: 0.25
– Isavuconazole: 0.25
– Micafungin: >32
Question 2: What treatment is recommended in the care of this patient?
Treatment: Voriconazole, patient will need to be on Voriconazole therapy indefinitely
The patient did improve after switching therapy to Voriconazole, but about 10 days later, the patient had worsening mental status; there was a concern for an acute stroke, so imaging of the head and neck was obtained. Just prior to the patient’s acute mental status decline, he did endorse visual hallucinations. Imaging of the head and neck did not demonstrate any evidence of an acute stroke, but it did show two new 0.3 cm and 0.2 cm fusiform aneurysms in the right ACA. A serum Voriconazole level was measured and came back elevated at 7.9 mcg/mL. The Voriconazole dose was decreased and the patient again improved with supportive ICU care. In addition to the likely contribution of Voriconazole neurotoxicity, it was felt that the patient’s acute mental status decline was due to hypercapnia from patient not tolerating a prolonged trach collar trial. A repeat serum Voriconazole level obtained about 5 days after the dose was adjusted came back lower at 3.53 mcg/mL. The patient’s clinical condition stabilized and Voriconazole therapy was continued.
With regards to the duration of treatment with Voriconazole, it was not initially clear what was the source of the Trichosporon asahii fungemia. Given the presence of multiple central lines (one of which had been in place for at least one month) and repeat negative blood cultures once central lines were removed/exchanged, it was initially felt as though the source was a central line. The ID consult team did speculate if the patient had fungal endocarditis given the presence of 3 minor Duke’s criteria: the patient had positive blood cultures for Trichosporon asahii, a predisposing cardiac condition of the mitral valve replacement, and possible vascular phenomenon with the fusiform aneurysms (representing mycotic aneurysms?). The ICU team did reach out to the Cardiology consult team about the possibility of doing a transesophageal echocardiogram, but the Cardiology team felt that the risks of doing the transesophageal echocardiogram outweighed the benefits given the patient’s acuity of illness and overall clinical complexity/comorbidities. As a result, given the fact that the patient was not clinically worsening and that he had 3 weeks of Voriconazole therapy after central line removal, the decision was made to stop Voriconazole therapy and closely monitor patient. However, the patient unfortunately had yet another clinical decline with increasing pressor requirements about 2 days after stopping Voriconazole therapy. Repeat blood cultures were obtained and again grew Trichosporon asahii.
At this point, Voriconazole therapy was resumed and repeat blood cultures were again obtained. The ICU team did briefly mention doing either a cardiac CT or PET-CT, but it was felt that doing either test would not change management as patient was not a surgical candidate and patient was now considered to very likely have Trichosporon asahii endocarditis and would need indefinite therapy.
In addition to the recurrent Trichosporon asahii fungemia/suspected Trichosporon asahii endocarditis, the patient’s hospital course was complicated by numerous other infections. The patient had recurrent Stenotrophomonas maltophilia HAP/VAP (though unclear if subsequent episodes represented true infection vs colonization), Stenotrophomonas maltophilia keratopathy/keratitis, Vancomycin-resistant Enterococcus bacteremia, and an unstageable sacral decubitus ulcer/wound that grew Stenotrophomonas maltophilia and Candida auris.
Discussion: (500 words)
This case highlights the possibility of fungemia related to non-Candida yeasts in immunocompromised patients.
Invasive Trichosporon asahii infections occur almost exclusively in immunocompromised hosts. Specifically, invasive Trichosporon spp infections are seen mostly in patients with hematological malignancies, other underlying malignancies, and/or prolonged periods of neutropenia; the presence of central venous catheters is also frequently implicated [1-5]. Our case was unique in that it occurred in a solid organ transplant recipient, albeit the patient had numerous other medical comorbidities. Unfortunately, the mortality rate for invasive Trichosporon spp infections is quite high, ranging anywhere from 50 to 80% .
Our case was distinct in that it brought up several interesting clinical pearls. First as noted above, Trichosporon asahii fungemia occurred in not the classic context; it occurred in a solid organ transplant patient with no history of malignancy or prolonged neutropenia. Secondly, although our patient had many risk factors for candidemia, the ID consult team appropriately had candidemia high on their differential and started patient on empiric Micafungin therapy, and discussions were already being started about removing/exchanging existing central lines, the patient did not actually grow a Candida spp in his blood but instead grew Trichosporon asahii. This highlights the importance of keeping one’s differential diagnosis broad when a yeast is noted on blood cultures. In other words, one should keep in mind other organisms such as Trichosporon spp, Cryptococcus spp, Geotrichum spp, etc., and not just anchor on a Candida spp.
Third, our patient very likely had fungal endocarditis as a complication of Trichosporon asahii fungemia. There are numerous case reports in the literature of endocarditis, specifically endocarditis of prosthetic heart valves, as a complication of invasive Trichosporon spp infections [6-9]. Though there is a paucity of randomized clinical trials for the treatment of invasive Trichosporon spp infections, the most successful and commonly used antifungal agent has been Voriconazole [10, 11]. Trichosporon spp are intrinsically resistant to echinocandins and Amphotericin susceptibilities can be variable [10, 11]. With regards to the management of Trichosporon spp/fungal endocarditis, there is again a scarcity of data. Both the 2015 AHA endocarditis guidelines and the 2023 ESC endocarditis guidelines recommend lifelong suppressive antifungal therapy, though the supporting evidence for these recommendations is based mostly on retrospective case reports and case series [12,13].
Lastly, our patient had a serious invasive fungal infection and had many other infectious complications, even though he was not in textbook period of “peak immunosuppression” that is typically thought of as occurring from months 2 through 6 to 12 post-transplant . On the contrary, our patient started to experience many of his infectious complications about 3 years post-transplant. Our patient’s multiple other medical comorbidities, including advanced CKD, type II diabetes, etc. likely had an additive effect on his overall immune status. This highlights the importance of the concept of the “net state of immunosuppression.” [16, 17]. Put another way, one always needs to consider all the factors contributing to an infectious risk, even if a patient is a few years or even several years out from a solid organ transplant.
In closing, Trichosporon spp infections have recently emerged as an increasingly recognized and common pathogen . While it is still relatively rare overall, it is rather concerning that this pathogen is becoming more commonplace, yet remains very difficult to treat with a high mortality rate and there is still much unknown about its pathogenicity. It is our hope that this case will raise awareness about this emerging fungal pathogen and will help providers, especially those who take care of immunocompromised patients, keep invasive Trichosporon spp infections in mind and higher on their differential.
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