No its Not Candida

Hem Updates

A 20-year-old male with newly diagnosed AML (NPM 1 mutated) was started on 3+7 induction. His baseline CT showed a patchy consolidation in the right middle lobe with ground glass opacities along with few ground glass opacities in the right lower lobe. In view of fever spikes (although low grade), he was started on posaconazole syrup therapeutic dose along with cefoperazone sulbactum on day 0 only. On day 5 high grade fever was noted for which his antibiotics were changed and hiked to meropenam and teicoplanin (empirically). Paired cultures from peripheral blood and PICC line came negative. In view of persistent high grade fever on day 7 NCCT thorax was done and Colistin was started (empirically). NCCT thorax showed normal study. Fever spikes came down in intensity and frequency and he became afebrile on day 10 of induction.

On day 17 patient showed breakthrough fever and hence teicoplanin was changed to tigecycline. Blood cultures were sent On day 19 PICC line blood culture showed yeast cell and hence PICC was removed and tip was sent for culture. CECT abdomen was done which showed multiple hypoattenuating microabscesses less than 1 cm in diameter disseminated throughout the hepatic parenchyma suggestive of hepatic candidiasis (shown in image below). Caspofungin was started on day 19 however fever spikes were persistent. On day 22 PICC tip culture was reported positive for trichosporon spp. 

Conventional Amphotericin B (@1mg/kg/day) was started and caspofungin was stopped. With persistent fever spikes (although low grade) IV Voriconazole was added (syp posaconazole stopped)  however due to severe hallucinations, it was stopped on day 26 and IV fluconazole 200 mg OD was started. Counts recovered (TLC = 3.17, ANC = 1.9) unsupported on day 29. Fever spikes resolved on day 33. Amphotericin was given for 14 days and stopped. Oral fluconazole was continued for next 3 months till completion of 3rd HIDAC cycle. 

Learning Point: Trichosporon spp can cause catheter mediated infections as ell as disseminated disease in immunocompromised patients and its clinico radiological presentation can mimic disseminated candidiasis. Echinocandins (eg caspofingin) are active against candida but not against trichosporon spp

Short point based review of Diagnosis & Treatment of infections caused by Trichosporon spp

  1. Trichosporon spp. are yeast-like anamorphic organisms that belong to the basidiomycetes yeasts.
  2. Invasive Trichosporonosis has been mainly documented in patients with hematological malignancies and other medical conditions associated with immunosuppression.
  3. Invasive infection occurs in three forms: disseminated disease (which is the most common presentation), disease localized to major organs, and infections that do not affect the tissues but are related to catheters.
  4. Voriconazole has been shown to be the most active drug against Trichosporonosis and should be the first-line treatment for patients that are neutropenic and have disseminated disease. Itraconazole and fluconazole are used as second line agent. 5-flucytosine has also been found to be active against it. 
  5. Most experts recommend combination therapy consisting of amphotericin and Voriconazole/5-flucytosine.
  6. It is important to remember that echinocandins have no effect when treating this fungal infection.
  7. Trichosporonosis resembles other invasive fungal infections such as invasive candidiasis.
  8. Prognosis of disseminated infection in neutropenic patients at the time of diagnosis largely depends on how rapidly neutropenia recovers. 
  9. In some patients this may develop into chronic phase requiring long term treatment. 
  10. Mortality rates as high as 40% to 60% have been reported in patients with severe invasive disease.

References:-

Recomended Review article: Invasive Trichosporon Infection: a Systematic Review on a Re-emerging Fungal Pathogen. Front. Microbiol., 17 October 2016  https://doi.org/10.3389/fmicb.2016.01629

Other references

  • Akagi, T., Yamaguti, K., Kawamura, T., Nakumura, T., Kubo, K., and Takemori, H. (2006). Breakthrough trichosporonosis in patients with acute myeloid leukemia receiving micafungin. Leuk. Lymphoma 47, 1182–1183. doi: 10.1080/10428190500272499
  • Antachopoulos, C., Papakonstantinou, E., Dotis, J., Bibashi, E., Tamiolaki, M., Koliouskas, D., et al. (2005). Fungemia due to Trichosporon asahii in a neutropenic child refractory to amphotericin B: clearance with voriconazole. J. Pediatr. Hematol. Oncol. 27, 283–285. doi: 10.1097/01.mph.0000164865.70522.d7
  • Arendrup, M. C., Boekhout, T., Akova, M., Meis, J. F., Cornely, O. A., Lortholary, O., et al. (2014). ESCMID/ECMM joint clinical guidelines for the diagnosis and management of rare invasive yeast infections. Clin. Microbiol. Infect. 20(Suppl .3), 76–98. doi: 10.1111/1469-0691.12360
  • Catherine E Foster, Morven S Edwards, Julienne Brackett, Deborah A Schady, C Mary Healy, Carol J Baker, Trichosporonosis in Pediatric Patients With a Hematologic Disorder, Journal of the Pediatric Infectious Diseases Society, Volume 7, Issue 3, September 2018, Pages 199–204,
  • Dua, Vikas MD*; Yadav, Satya P. DCH, DNB*; Oberoi, Jaswinder MD†; Sachdeva, Anupam DCH, MD* Successful Treatment of Trichosporon asahii Infection With Voriconazole After Bone Marrow Transplant, Journal of Pediatric Hematology/Oncology: April 2013 – Volume 35 – Issue 3 – p 237-238 doi: 10.1097/MPH.0b013e318279b21b

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