© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273
Case report
Disseminated Trichosporon infection in a renal transplant recipient V. Chaitanya, B. Sangeetha Lakshmi, A.C. Venkata Kumar, M. Hari Krishna Reddy, R. Ram, V. Siva Kumar. Disseminated Trichosporon infection in a renal transplant recipient. Transpl Infect Dis 2015: 17: 605–609. All rights reserved Abstract: Trichosporon species are basidiomycetous yeast-like anamorphic organisms (Basidiomycota, Hymenomycetes, Tremelloidae, Trichosporonales) that are widely distributed in nature. Trichosporon species colonize the skin and gastrointestinal tract of humans. We present a report of disseminated Trichosporon in a renal allograft recipient. Our patient satisfied the definitions of both “proven invasive trichosporonosis” and “probable pulmonary infection.” Only 2 reports of disseminated Trichosporon infection in renal transplant recipients, to our knowledge, have been published.
V. Chaitanya, B. Sangeetha Lakshmi, A.C. Venkata Kumar, M. Hari Krishna Reddy, R. Ram, V. Siva Kumar Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India Key words: dissemination; Trichosporon infection; renal transplant recipient; voriconazole Correspondence to: R. Ram, MD, DM, Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India Tel: 09848246364 Tel2: 09493547803 Fax: N/A E-mail: [email protected]
Received 25 January 2015, revised 2 April 2015, accepted for publication 21 May 2015 DOI: 10.1111/tid.12412 Transpl Infect Dis 2015: 17: 605–609
Trichosporon species are basidiomycetous yeast-like anamorphic organisms (Basidiomycota, Hymenomycetes, Tremelloidae, Trichosporonales) that are widely distributed in nature (1). Trichosporon species colonize the skin and the gastrointestinal tract of humans (2, 3), and have long been known as the cause of superficial infections, such as white piedra, a distal infection of the hair shaft (4), onychomycosis, and otomycosis. Occasional reports have appeared on deep-seated Trichosporon infection, such as lower limb cellulitis (5) and uterine infection (6) in immunocompetent patients. Trichosporon species are increasingly recognized as a cause of systemic illness in immunocompromised patients (7). Hematologic malignancies are the bestdescribed risk factors for trichosporonosis (7). The majority of these patients received cytotoxic chemotherapy resulting in neutropenia (7). The other risk factors were corticosteroid use, hemochromatosis, other deficiencies of granulocyte function, prosthetic valve surgery, chronic active hepatitis, intravenous drug abuse, and end-stage renal disease (1, 8). We
present a report of disseminated Trichosporon in a renal allograft recipient.
Case report A 45-year-old man was diagnosed with membranoproliferative glomerulonephritis 18 years ago. He received prednisolone for 120 months. The initial doses were 40 mg/m2/alternate day; later, it was tapered to 10 mg/alternate day. He also received angiotensinconverting enzyme inhibitors, dipyridamole, and aspirin. He progressed to end-stage renal disease 15 years after diagnosis. After 1 month of hemodialysis via left radiocephalic arteriovenous fistula, he underwent renal transplantation. His wife was the donor. He received basiliximab 20 mg in 2 doses, the first on day 0 and the second dose on day 4; injection of methylprednisolone 15 mg/kg/day for the first 3 days, followed by prednisolone 20 mg/day, tacrolimus 0.05 mg/kg/day, and mycophenolate mofetil
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Chaitanya et al: Disseminated Trichosporon
1.0 g twice a day. The patient received prophylaxis with valganciclovir, fluconazole, and cotrimoxazoletrimethoprim combination for the first 3 months. At the end of 6 months, the immunosuppression was reduced to prednisolone 10 mg/day, tacrolimus 0.03 mg/kg/day, and mycophenolate mofetil 750 mg twice a day. At 9 months after renal transplantation, the patient suffered an injury with subsequent swelling of right little finger (supplementary Figure S1); it later became warm, red, and tender. The pus from the swelling revealed fungal elements on KOH mount and grew Trichosporon on Sabouraud dextrose agar. He was started on oral voriconazole, initiated at a dose of 200 mg twice a day. During the next 2 weeks, the patient developed new lesions on the extensor surface of right upper limb near the elbow, on the lateral surface of his right thigh, and painful restriction of the right first metatarsophalangeal joint (supplementary Figures S2, S3, and S4). Pus was aspirated from these lesions; from the right first metatarsophalangeal joint, it was aspirated with the help of ultrasound. The pus from all these sites grew Trichosporon. After 3 weeks of therapy, the lesion on the lateral surface of right thigh has widened and became more painful. It was drained under local anesthesia, and pus from this lesion also grew Trichosporon. He also developed cough and wheezing, with bronchial breathing in the left infraclavicular region. Chest radiograph revealed left mid zone consolidation (Fig. 1), which was later confirmed by computed tomography scan (supplementary Figure S5). Culture of specimen from ultrasound-guided aspiration of this lung lesion also grew Trichosporon. The patient was continued on voriconazole for 6 weeks. At the end of 6 weeks, all lesions, including the lung lesion, had subsided, except for the lesion in the right thigh, which was managed by debridement and regular dressing. Serum tacrolimus levels were measured every week. The serial values showed an increasing trend and reached maximum value of 11.1 ng/mL. The doses of tacrolimus were reduced to maintain the levels between 4 and 7 ng/mL. The important laboratory investigations of the patient were serum creatinine: 0.7?0.9?1.3?1.4 mg/dL, blood urea: 24?36?54?72 mg/dL, serum sodium: 134 mEq/L, serum potassium: 4.5 mEq/L, serum bilirubin: 0.6 mg/L, alanine aminotransferase: 24?54? 73?115 IU/L, aspartate aminotransferase: 28?45? 98?142 IU/L, alkaline phosphatase: 132?145?150? 129 IU/L, hemoglobin: 13.5?10.5 g/dL, and total leukocyte count: 11800?7500 per mm3. Ultrasound
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Fig. 1. Chest radiograph showing left mid zone consolidation.
revealed renal allograft size of 10.5 9 4.5 cm. When the patient was on voriconazole, transaminase levels rose and the patient complained of blurring of vision and increased sensitivity to light. At the end of 6 months, the lesion in the right thigh had healed. The important laboratory investigations were serum creatinine: 1.5 mg/dL, serum bilirubin: 0.8 mg/L, alanine aminotransferase: 28 IU/L, aspartate aminotransferase: 32 IU/L, alkaline phosphatase: 74 IU/L, hemoglobin: 11.0 g/dL, and total leukocyte count: 5500 per mm3.
Discussion The definitions of opportunistic invasive fungal infections were published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infection Cooperative Group and the National Institute of Allergy and Infectious Disease Mycoses Study Group (9). Our patient’s infection was in accordance with the definitions of proven invasive trichosporonosis provided by this group (9). Our patient’s lung infection was also in agreement with the criteria for diagnosis of “probable” pulmonary infection of Trichosporon proposed by Girmenia et al. (10). Only 2 reports of disseminated Trichosporon infection in renal transplant recipients (RTR) have been published, to our knowledge. Table 1 summarizes the published articles on Trichosporon infection in RTR (11–15). A report was published on funguria in RTR (16); over an 8-year period, 11 RTR experienced Trichosporon beigelii funguria. All patients were receiving immunosuppressive therapy consisting of prednisone and/or
Transplant Infectious Disease 2015: 17: 605–609
Chaitanya et al: Disseminated Trichosporon
Published articles on Trichosporon infection in renal transplant recipients
Reference
Age in years
Immunosuppression
Site of infection
Duration after transplantation
Trichosporon species
Treatment
Outcome
(11)
45
–
Disseminated; multiple reddish nodules on the trunk and face
6 months
T. beigelii
Fluconazole
Recovered
(12)*
64
Prednisolone, mycophenolate mofetil, tacrolimus
Disseminated; several painful, reddish-purple, pruritic papules (diameter 3–5 mm) on his right knee, lateral calf, and the dorsal surface of his right foot
6 months
T. mucoides
Fluconazole
Recovered
(13)
39
Basiliximab, prednisolone, tacrolimus, mycophenolate sodium
Surgical wound infection
Immediate postoperative period
Trichosporon species
Voriconazole
Recovered
(14)
40
–
Ruptured vascular anastomosis
Postoperative day 18
Trichosporon species
Surgery
Allograft removed
(15)
67
Prednisolone, tacrolimus, mycophenolate mofetil
Pneumonia
8 years
T. asahii
Caspofungin
Died
*Heart and kidney transplantation; the rest of the patients were kidney transplant recipients.
Table 1
azathioprine and/or cyclosporine. The majority of patients had funguria within the first 6 months after engraftment. The risk factors for funguria included urinary tract indwelling devices in 5 patients and broadspectrum systemic antibacterial therapy in 6 patients. Three patients complained of symptoms of urinary tract infection, and 4 patients experienced only fever. A bladder fungal ball was found in 1 patient. The authors concluded in their report that T. beigelii funguria in RTR was seldom invasive. In a microbiology study (17) on solid organ transplant recipients, Trichosporon asahii was found in 26 clinical samples taken from 18 patients and 1 organ donor out of 263 liver, kidney, and simultaneous pancreas–kidney transplant recipients, and from 26 organ donors. Asymptomatic colonization of urinary tract was observed in most of the patients in whom T. asahii was positively cultured. Disseminated Trichosporon infections are usually associated with 2 species, Trichosporon capitatum and T. beigelii. After the taxonomic classification of members of the genus Trichosporon was revised, T. capitatum is no longer a member of the genus Trichosporon, but is now classified as either Blastoschizomyces capitatus or Geotrichum capitatus. According to the new taxonomic classification, T. asahii and Trichosporon mucoides are associated with life-threatening infections, and Trichosporon cutaneum (T. beigelii), Trichosporon
inkin, and Trichosporon ovoides are associated with superficial infections (12). Although our patient was not neutropenic, which is a traditional risk factor described in the literature (7), he was on immunosuppression and also had suffered an injury that served as a portal of entry of the Trichosporon for subsequent dissemination. In the majority of patients, the portals of entry were the respiratory and gastrointestinal systems, central venous catheters, or percutaneous vascular devices (2, 18). In vitro studies (19–21) have demonstrated the effectiveness of voriconazole against Trichosporon. Furthermore, Rodriguez-Tudela et al. (19) demonstrated that all T. asahii isolates tested had amphotericin B (AmB) minimum inhibitory concentrations (MICs) of ≥2 lg/mL. They also observed that the majority of Trichosporon coremiiforme and Trichosporon faecale strains were also resistant to AmB. The same group also published a study in which voriconazole and posaconazole were shown to have the best in vitro antifungal activity against most Trichosporon species (22). Chagas-Neto et al. (20) found that voriconazole generated the lowest MIC values against all strains of Trichosporon (20). The same study concluded that the triazoles were generally more effective than AmB. In another study (21), voriconazole exhibited excellent
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in vitro activity against most of the strains tested, including isolates resistant to fluconazole, echinocandins, and AmB. Triazoles are currently the drug of choice for the treatment of Trichosporon infections. The clinical experience with triazoles is encouraging. Previously reported patients were also successfully treated using voriconazole, posaconazole, and fluconazole (11–13, 23). A recent study with head-to-head comparison of 5 triazoles has shown that the most active is voriconazole, followed by itraconazole, posaconazole, isavuconazole, and fluconazole (24). Over the years, high-dose AmB deoxycholate has been the most common treatment for invasive trichosporonosis. However, many breakthrough cases have occurred on this therapy (25, 26). Treatment failures have also been reported with lipid preparations of AmB (27). Finally, echinocandins alone have little to no activity against Trichosporon species and are not recommended for trichosporonosis treatment (28). However, it is intriguing that 2 studies (26, 27) found that a combination of echinocandin with AmB or azoles appears to have some in vitro and in vivo synergistic antifungal effects. In the former study (26) using a murine model of disseminated infection caused by T. asahii, the combination of micafungin with AmB showed a synergistic effect and demonstrated a higher degree of efficacy in prolonging survival and reducing the kidney fungal burden than either agent alone. The combination of micafungin with flucytosine (5-fluorocytosine or 5-FC) was able to reduce the kidney fungal burden significantly in comparison with results achieved with the administration of either drug alone. Successful treatment of peritoneal dialysis-associated peritonitis caused by T. inkin was reported using caspofungin monotherapy (29). The available data on the therapeutic role of 5-FC in trichosporonosis are limited and controversial. In vitro data suggest that a large proportion of Trichosporon strains may be resistant to 5-FC (20, 30). In contrast, some authors report good results in the treatment of trichosporonosis with a combination therapy of 5-FC and AmB (10). Trichosporon species is being increasingly recognized as a cause of invasive mycoses in contemporary medicine. In patients with malignant hematologic diseases, this genus has been reported as the second most common agent of disseminated yeast infections, behind only the genus Candida. The reported mortality of invasive Trichosporon infection is between 50% and 80%, despite antifungal therapy (1).
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Acknowledgements: Conflicts of interests: None. Disclosures: None.
References 1. Colombo AL, Padovan AC, Chaves GM. Current knowledge of Trichosporon spp. and trichosporonosis. Clin Microbiol Rev 2011; 24 (4): 682–700. 2. Walsh TJ, Melcher GP, Lee JW, Pizzo PA. Infections due to Trichosporon species: new concepts in mycology, pathogenesis, diagnosis and treatment. Curr Top Med Mycol 1993; 5: 79–113. 3. Pritchard RC, Muir DB. Trichosporon beigelii: survey of isolates from clinical material. Pathology 1985; 17: 20–23. 4. Assaf RR, Weil ML. The superficial mycoses. Dermatol Clin 1996; 14 (1): 57–67. 5. Bakra S, Tsouma I, Kouskouni E. Fatal lower limb infection by Trichosporon asahii in an immunocompetent patient. Acta Dermatovenerol Croat 2013; 21 (4): 241–244. 6. Chan RM, Lee P, Wroblewski J. Deep-seated trichosporonosis in an immunocompetent patient: a case report of uterine trichosporonosis. Clin Infect Dis 2000; 31 (2): 621. 7. Tashiro T, Nagai H, Kamberi P, et al. Disseminated Trichosporon beigelii infection in patients with malignant diseases: immunohistochemical study and review. Eur J Clin Microbiol Infect Dis 1994; 13 (3): 218–224. 8. Walsh TJ. Trichosporonosis. Infect Dis Clin North Am 1989; 3 (1): 43–52. 9. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–1821. 10. Girmenia C, Pagano L, Martino B, et al. Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature. J Clin Microbiol 2005; 43: 1818–1828. 11. Mirza SH. Disseminated Trichosporon beigelii infection causing skin lesions in a renal transplant patient. J Infect 1993; 27 (1): 67–70. 12. Nettles RE, Nichols LS, Bell-McGuinn K, Pipeling MR, Scheel PJ Jr, Merz WG. Successful treatment of Trichosporon mucoides infection with fluconazole in a heart and kidney transplant recipient. Clin Infect Dis 2003; 36 (4): E63–E66. 13. Sundaram M, Anandbabu K, Basu G, Devasia A, Tamilarasi V. Trichosporon surgical wound infection in a renal allograft recipient successfully treated with voriconazole. Transplantation 2010; 90 (5): 588–589. 14. Fadhil RA, Al-Thani H, Al-Maslamani Y, Ali O. Trichosporon fungal arteritis causing rupture of vascular anastamosis after commercial kidney transplantation: a case report and review of literature. Transplant Proc 2011; 43 (2): 657–659. 15. Yang MF, Gao HN, Li LJ. A fatal case of Trichosporon asahii fungemia and pneumonia in a kidney transplant recipient during caspofungin treatment. Ther Clin Risk Manag 2014; 30 (10): 759–762.
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16. Lussier N, Laverdiere M, Delorme J, Weiss K, Dandavino R. Trichosporon beigelii funguria in renal transplant recipients. Clin Infect Dis 2000; 31 (5): 1299–1301. 17. Netsvyetayeva I, Swoboda-Kopec E, Paczek L, et al. Trichosporon asahii as a prospective pathogen in solid organ transplant recipients. Mycoses 2009; 52 (3): 263–265. 18. Ebright JR, Fairfax MR, Vazquez JA. Trichosporon asahii, a nonCandida yeast that caused fatal septic shock in a patient without cancer or neutropenia. Clin Infect Dis 2001; 33 (5): E28–E30. 19. Rodriguez-Tudela JL, Diaz-Guerra TM, Mellado E, et al. Susceptibility patterns and molecular identification of Trichosporon species. Antimicrob Agents Chemother 2005; 49: 4026–4034. 20. Chagas-Neto TC, Chaves GM, Melo AS, Colombo AL. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing. J Clin Microbiol 2009; 47: 1074–1081. 21. Ruan SY, Chien JY, Hsueh PR. Invasive trichosporonosis caused by Trichosporon asahii and other unusual Trichosporon species at a medical center in Taiwan. Clin Infect Dis 2009; 49: 11–17. 22. Araujo Ribeiro M, Alastruey-Izquierdo A, Gomez-Lopez A, Rodriguez-Tudela JL, Cuenca-Estrella M. Molecular identification and susceptibility testing of Trichosporon isolates from a Brazilian hospital. Rev Iberoam Micol 2008; 25: 221–225. 23. Falk R, Wolf DG, Shapiro M, Polacheck I. Multidrug-resistant Trichosporon asahii isolates are susceptible to voriconazole. J Clin Microbiol 2003; 41 (2): 911. 24. Hazirolan G, Canton E, Sahin S, Arikan-Akdagli S. Head-to-head comparison of inhibitory and fungicidal activities of fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole against clinical isolates of Trichosporon asahii. Antimicrob Agents Chemother 2013; 57 (10): 4841–4847. 25. Krcmery V, Krupova I, Denning DW. Invasive yeast infections other than Candida spp. in acute leukaemia. J Hosp Infect 1999; 41 (3): 181–194.
26. Serena C, Pastor FJ, Gilgado F, Mayayo E, Guarro J. Efficacy of micafungin in combination with other drugs in a murine model of disseminated trichosporonosis. Antimicrob Agents Chemother 2005; 49 (2): 497–502. 27. Bassetti M, Bisio F, Di Biagio A, et al. Trichosporon asahii infection treated with caspofungin combined with liposomal amphotericin B. J Antimicrob Chemother 2004; 54 (2): 575–577. 28. Walsh TJ, Groll A, Hiemenz J, Fleming R, Roilides E, Anaissie E. Infections due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect 2004; 10: 44–66. 29. Madariaga MG, Tenorio A, Proia L. Trichosporon inkin peritonitis treated with caspofungin. J Clin Microbiol 2003; 41 (12): 5827–5829. 30. Mekha N, Sugita T, Ikeda R, et al. Genotyping and antifungal drug susceptibility of the pathogenic yeast Trichosporon asahii isolated from Thai patients. Mycopathologia 2010; 169: 67–70.
Supporting Information Supporting Information may be found online with this article: Figure S1. Inflamed right little finger. Figure S2. Lesion on extensor surface of right upper limb near the elbow. Figure S3. Lesion on the lateral surface of right thigh. Figure S4. Inflamed right first metatarsophalangeal joint. Figure S5. Computed tomography scan of chest: left mid zone consolidation.
Transplant Infectious Disease 2015: 17: 605–609
609
Case report
Disseminated Trichosporon infection in a renal transplant recipient V. Chaitanya, B. Sangeetha Lakshmi, A.C. Venkata Kumar, M. Hari Krishna Reddy, R. Ram, V. Siva Kumar. Disseminated Trichosporon infection in a renal transplant recipient. Transpl Infect Dis 2015: 17: 605–609. All rights reserved Abstract: Trichosporon species are basidiomycetous yeast-like anamorphic organisms (Basidiomycota, Hymenomycetes, Tremelloidae, Trichosporonales) that are widely distributed in nature. Trichosporon species colonize the skin and gastrointestinal tract of humans. We present a report of disseminated Trichosporon in a renal allograft recipient. Our patient satisfied the definitions of both “proven invasive trichosporonosis” and “probable pulmonary infection.” Only 2 reports of disseminated Trichosporon infection in renal transplant recipients, to our knowledge, have been published.
V. Chaitanya, B. Sangeetha Lakshmi, A.C. Venkata Kumar, M. Hari Krishna Reddy, R. Ram, V. Siva Kumar Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India Key words: dissemination; Trichosporon infection; renal transplant recipient; voriconazole Correspondence to: R. Ram, MD, DM, Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India Tel: 09848246364 Tel2: 09493547803 Fax: N/A E-mail: [email protected]
Received 25 January 2015, revised 2 April 2015, accepted for publication 21 May 2015 DOI: 10.1111/tid.12412 Transpl Infect Dis 2015: 17: 605–609
Trichosporon species are basidiomycetous yeast-like anamorphic organisms (Basidiomycota, Hymenomycetes, Tremelloidae, Trichosporonales) that are widely distributed in nature (1). Trichosporon species colonize the skin and the gastrointestinal tract of humans (2, 3), and have long been known as the cause of superficial infections, such as white piedra, a distal infection of the hair shaft (4), onychomycosis, and otomycosis. Occasional reports have appeared on deep-seated Trichosporon infection, such as lower limb cellulitis (5) and uterine infection (6) in immunocompetent patients. Trichosporon species are increasingly recognized as a cause of systemic illness in immunocompromised patients (7). Hematologic malignancies are the bestdescribed risk factors for trichosporonosis (7). The majority of these patients received cytotoxic chemotherapy resulting in neutropenia (7). The other risk factors were corticosteroid use, hemochromatosis, other deficiencies of granulocyte function, prosthetic valve surgery, chronic active hepatitis, intravenous drug abuse, and end-stage renal disease (1, 8). We
present a report of disseminated Trichosporon in a renal allograft recipient.
Case report A 45-year-old man was diagnosed with membranoproliferative glomerulonephritis 18 years ago. He received prednisolone for 120 months. The initial doses were 40 mg/m2/alternate day; later, it was tapered to 10 mg/alternate day. He also received angiotensinconverting enzyme inhibitors, dipyridamole, and aspirin. He progressed to end-stage renal disease 15 years after diagnosis. After 1 month of hemodialysis via left radiocephalic arteriovenous fistula, he underwent renal transplantation. His wife was the donor. He received basiliximab 20 mg in 2 doses, the first on day 0 and the second dose on day 4; injection of methylprednisolone 15 mg/kg/day for the first 3 days, followed by prednisolone 20 mg/day, tacrolimus 0.05 mg/kg/day, and mycophenolate mofetil
605
Chaitanya et al: Disseminated Trichosporon
1.0 g twice a day. The patient received prophylaxis with valganciclovir, fluconazole, and cotrimoxazoletrimethoprim combination for the first 3 months. At the end of 6 months, the immunosuppression was reduced to prednisolone 10 mg/day, tacrolimus 0.03 mg/kg/day, and mycophenolate mofetil 750 mg twice a day. At 9 months after renal transplantation, the patient suffered an injury with subsequent swelling of right little finger (supplementary Figure S1); it later became warm, red, and tender. The pus from the swelling revealed fungal elements on KOH mount and grew Trichosporon on Sabouraud dextrose agar. He was started on oral voriconazole, initiated at a dose of 200 mg twice a day. During the next 2 weeks, the patient developed new lesions on the extensor surface of right upper limb near the elbow, on the lateral surface of his right thigh, and painful restriction of the right first metatarsophalangeal joint (supplementary Figures S2, S3, and S4). Pus was aspirated from these lesions; from the right first metatarsophalangeal joint, it was aspirated with the help of ultrasound. The pus from all these sites grew Trichosporon. After 3 weeks of therapy, the lesion on the lateral surface of right thigh has widened and became more painful. It was drained under local anesthesia, and pus from this lesion also grew Trichosporon. He also developed cough and wheezing, with bronchial breathing in the left infraclavicular region. Chest radiograph revealed left mid zone consolidation (Fig. 1), which was later confirmed by computed tomography scan (supplementary Figure S5). Culture of specimen from ultrasound-guided aspiration of this lung lesion also grew Trichosporon. The patient was continued on voriconazole for 6 weeks. At the end of 6 weeks, all lesions, including the lung lesion, had subsided, except for the lesion in the right thigh, which was managed by debridement and regular dressing. Serum tacrolimus levels were measured every week. The serial values showed an increasing trend and reached maximum value of 11.1 ng/mL. The doses of tacrolimus were reduced to maintain the levels between 4 and 7 ng/mL. The important laboratory investigations of the patient were serum creatinine: 0.7?0.9?1.3?1.4 mg/dL, blood urea: 24?36?54?72 mg/dL, serum sodium: 134 mEq/L, serum potassium: 4.5 mEq/L, serum bilirubin: 0.6 mg/L, alanine aminotransferase: 24?54? 73?115 IU/L, aspartate aminotransferase: 28?45? 98?142 IU/L, alkaline phosphatase: 132?145?150? 129 IU/L, hemoglobin: 13.5?10.5 g/dL, and total leukocyte count: 11800?7500 per mm3. Ultrasound
606
Fig. 1. Chest radiograph showing left mid zone consolidation.
revealed renal allograft size of 10.5 9 4.5 cm. When the patient was on voriconazole, transaminase levels rose and the patient complained of blurring of vision and increased sensitivity to light. At the end of 6 months, the lesion in the right thigh had healed. The important laboratory investigations were serum creatinine: 1.5 mg/dL, serum bilirubin: 0.8 mg/L, alanine aminotransferase: 28 IU/L, aspartate aminotransferase: 32 IU/L, alkaline phosphatase: 74 IU/L, hemoglobin: 11.0 g/dL, and total leukocyte count: 5500 per mm3.
Discussion The definitions of opportunistic invasive fungal infections were published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infection Cooperative Group and the National Institute of Allergy and Infectious Disease Mycoses Study Group (9). Our patient’s infection was in accordance with the definitions of proven invasive trichosporonosis provided by this group (9). Our patient’s lung infection was also in agreement with the criteria for diagnosis of “probable” pulmonary infection of Trichosporon proposed by Girmenia et al. (10). Only 2 reports of disseminated Trichosporon infection in renal transplant recipients (RTR) have been published, to our knowledge. Table 1 summarizes the published articles on Trichosporon infection in RTR (11–15). A report was published on funguria in RTR (16); over an 8-year period, 11 RTR experienced Trichosporon beigelii funguria. All patients were receiving immunosuppressive therapy consisting of prednisone and/or
Transplant Infectious Disease 2015: 17: 605–609
Chaitanya et al: Disseminated Trichosporon
Published articles on Trichosporon infection in renal transplant recipients
Reference
Age in years
Immunosuppression
Site of infection
Duration after transplantation
Trichosporon species
Treatment
Outcome
(11)
45
–
Disseminated; multiple reddish nodules on the trunk and face
6 months
T. beigelii
Fluconazole
Recovered
(12)*
64
Prednisolone, mycophenolate mofetil, tacrolimus
Disseminated; several painful, reddish-purple, pruritic papules (diameter 3–5 mm) on his right knee, lateral calf, and the dorsal surface of his right foot
6 months
T. mucoides
Fluconazole
Recovered
(13)
39
Basiliximab, prednisolone, tacrolimus, mycophenolate sodium
Surgical wound infection
Immediate postoperative period
Trichosporon species
Voriconazole
Recovered
(14)
40
–
Ruptured vascular anastomosis
Postoperative day 18
Trichosporon species
Surgery
Allograft removed
(15)
67
Prednisolone, tacrolimus, mycophenolate mofetil
Pneumonia
8 years
T. asahii
Caspofungin
Died
*Heart and kidney transplantation; the rest of the patients were kidney transplant recipients.
Table 1
azathioprine and/or cyclosporine. The majority of patients had funguria within the first 6 months after engraftment. The risk factors for funguria included urinary tract indwelling devices in 5 patients and broadspectrum systemic antibacterial therapy in 6 patients. Three patients complained of symptoms of urinary tract infection, and 4 patients experienced only fever. A bladder fungal ball was found in 1 patient. The authors concluded in their report that T. beigelii funguria in RTR was seldom invasive. In a microbiology study (17) on solid organ transplant recipients, Trichosporon asahii was found in 26 clinical samples taken from 18 patients and 1 organ donor out of 263 liver, kidney, and simultaneous pancreas–kidney transplant recipients, and from 26 organ donors. Asymptomatic colonization of urinary tract was observed in most of the patients in whom T. asahii was positively cultured. Disseminated Trichosporon infections are usually associated with 2 species, Trichosporon capitatum and T. beigelii. After the taxonomic classification of members of the genus Trichosporon was revised, T. capitatum is no longer a member of the genus Trichosporon, but is now classified as either Blastoschizomyces capitatus or Geotrichum capitatus. According to the new taxonomic classification, T. asahii and Trichosporon mucoides are associated with life-threatening infections, and Trichosporon cutaneum (T. beigelii), Trichosporon
inkin, and Trichosporon ovoides are associated with superficial infections (12). Although our patient was not neutropenic, which is a traditional risk factor described in the literature (7), he was on immunosuppression and also had suffered an injury that served as a portal of entry of the Trichosporon for subsequent dissemination. In the majority of patients, the portals of entry were the respiratory and gastrointestinal systems, central venous catheters, or percutaneous vascular devices (2, 18). In vitro studies (19–21) have demonstrated the effectiveness of voriconazole against Trichosporon. Furthermore, Rodriguez-Tudela et al. (19) demonstrated that all T. asahii isolates tested had amphotericin B (AmB) minimum inhibitory concentrations (MICs) of ≥2 lg/mL. They also observed that the majority of Trichosporon coremiiforme and Trichosporon faecale strains were also resistant to AmB. The same group also published a study in which voriconazole and posaconazole were shown to have the best in vitro antifungal activity against most Trichosporon species (22). Chagas-Neto et al. (20) found that voriconazole generated the lowest MIC values against all strains of Trichosporon (20). The same study concluded that the triazoles were generally more effective than AmB. In another study (21), voriconazole exhibited excellent
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in vitro activity against most of the strains tested, including isolates resistant to fluconazole, echinocandins, and AmB. Triazoles are currently the drug of choice for the treatment of Trichosporon infections. The clinical experience with triazoles is encouraging. Previously reported patients were also successfully treated using voriconazole, posaconazole, and fluconazole (11–13, 23). A recent study with head-to-head comparison of 5 triazoles has shown that the most active is voriconazole, followed by itraconazole, posaconazole, isavuconazole, and fluconazole (24). Over the years, high-dose AmB deoxycholate has been the most common treatment for invasive trichosporonosis. However, many breakthrough cases have occurred on this therapy (25, 26). Treatment failures have also been reported with lipid preparations of AmB (27). Finally, echinocandins alone have little to no activity against Trichosporon species and are not recommended for trichosporonosis treatment (28). However, it is intriguing that 2 studies (26, 27) found that a combination of echinocandin with AmB or azoles appears to have some in vitro and in vivo synergistic antifungal effects. In the former study (26) using a murine model of disseminated infection caused by T. asahii, the combination of micafungin with AmB showed a synergistic effect and demonstrated a higher degree of efficacy in prolonging survival and reducing the kidney fungal burden than either agent alone. The combination of micafungin with flucytosine (5-fluorocytosine or 5-FC) was able to reduce the kidney fungal burden significantly in comparison with results achieved with the administration of either drug alone. Successful treatment of peritoneal dialysis-associated peritonitis caused by T. inkin was reported using caspofungin monotherapy (29). The available data on the therapeutic role of 5-FC in trichosporonosis are limited and controversial. In vitro data suggest that a large proportion of Trichosporon strains may be resistant to 5-FC (20, 30). In contrast, some authors report good results in the treatment of trichosporonosis with a combination therapy of 5-FC and AmB (10). Trichosporon species is being increasingly recognized as a cause of invasive mycoses in contemporary medicine. In patients with malignant hematologic diseases, this genus has been reported as the second most common agent of disseminated yeast infections, behind only the genus Candida. The reported mortality of invasive Trichosporon infection is between 50% and 80%, despite antifungal therapy (1).
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Acknowledgements: Conflicts of interests: None. Disclosures: None.
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Supporting Information Supporting Information may be found online with this article: Figure S1. Inflamed right little finger. Figure S2. Lesion on extensor surface of right upper limb near the elbow. Figure S3. Lesion on the lateral surface of right thigh. Figure S4. Inflamed right first metatarsophalangeal joint. Figure S5. Computed tomography scan of chest: left mid zone consolidation.
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