Infectious Diseases Section, Veterans Affairs Medical Center, Washington, DC, USA.
Received 26 November, 2007
Accepted 4 December, 2007
Fatal trichosporonosis developed in an advanced AIDS patient after prolonged intravenous antibiotics for infections related to injection drug use. This is the first review of the disease interaction between Trichosporon and HIV infection.
Trichosporon, a basidiomycetes yeast found on human skin, is an important cause of invasive mycosis . Trichosporonosis has been considered a disease of severely immunosuppressed patients with hematological malignancies rendered neutropenic by myeloablative chemotherapy . Disseminated infection has, however, been reported in patients with solid organ transplants , solid organ tumors , Job's syndrome , and prolonged illnesses in intensive care units [9,10]. We report an unusual case of Trichosporon fungemia in an AIDS patient and review the interaction between trichosporonosis and HIV.
A 49-year-old AIDS patient with diabetes mellitus and hepatitis C had a complicated course because of injection drug use, medical non-adherence, progression with a CD4 cell count of 5 cells/μl and HIV-RNA level of 86 551 copies/ml and declining cognition as a result of AIDS-related dementia complex, and several hospitalizations for methicillin-resistant Staphylococcus aureus bacteremia, pneumonia and empyema. During treatment of leg abscesses with antibiotics via a central venous catheter, blood cultures (three sets) grew Candida glabrata. Five days later, Trichosporon grew from a blood culture (Vitek2; bioMeriéux, Durham, North Carolina, USA) and was confirmed by morphology on cornmeal agar but could not be speciated. At that time, his leukocyte count was 3500 cells/μl with an absolute neutrophil count (ANC) of 2300 cells/μl. His central venous catheter was removed, and he received amphotericin (6 days) followed by voriconazole (8 days). Subsequently, blood cultures (four sets) yielded no growth; transthoracic echocardiogram showed no evidence of infective endocarditis.
Two months later, he was treated with a 3-week course of broad-spectrum antibiotics for right leg cellulitis. His leukocyte count was 4700 cells/μl with an ANC of 3900 cells/μl. Trichosporon was identified from a single blood culture obtained during a febrile transfusion reaction, but the patient did not return for evaluation or treatment. He presented, however, with recrudescent cellulitis and altered mentation 2 weeks later. All repeat blood cultures (four sets) remained sterile, but serum cryptococcal antigen was detected at 1: 8-titer (Immy Latex-Crypto Antigen; Immuno-Mycologics, Inc., Norman, Oklahoma, USA), as Trichosporon produces a crossreacting extracellular matrix similar in composition to the polysaccharide capsule of Cryptococcus neoformans . Although the patient improved during a 2-week course of antibiotics and amphotericin B, his fever returned 8 days after antimicrobial drugs were stopped. Trichosporon asahii was identified from blood cultures, confirmed by morphological examination on cornmeal agar and speciated by biochemical analysis (API 20C; Analytab Products, Plainview, New York, USA). The patient was treated with amphotericin B and fluconazole, but T. asahii fungemia and funguria persisted before his death in a hospice unit.
Trichosporon beigelii had been recognized as the only pathogenic species until reclassification of Trichosporon into 17 species, of which six were considered human pathogens . Up to 88% of deep-seated Trichosporon infections are caused by T. asahii ; therefore, most previous T. beigelii reports would probably have been reclassified as T. asahii.
From the English language medical literature, we found seven additional cases of deep-seated trichosporonosis and HIV infection [11–15] but excluded two for insufficient evidence for the pathogenic role of Trichosporon. As summarized in Table 1, all patients had a previous AIDS-defining illness and a CD4 cell count of less than 200 cells/μl when reported. Four patients had an intravascular or intraperitoneal catheter, and the use of an intravascular catheter was inferred in another patient on systemic ganciclovir and antineoplastic agents for Kaposi's sarcoma . Five patients had received long or multiple courses of antibiotics for bacterial and viral infections. Only one was neutropenic among the five cases with reported granulocyte counts. Three patients were treated with amphotericin B, one with fluconazole and two with a combination of these agents. The mortality rate was high (50%), although one patient discontinued therapy in a hospice unit.
The patients reported here offer several notable distinctions from previous series. Six patients had advanced AIDS. Most were not neutropenic, and their infections were confined to the bloodstream or peritoneal cavity without metastatic foci. Most cases had an indwelling catheter from which Trichosporon was initially isolated, and those with a documented catheter removal survived. Therefore, trichosporonosis in HIV patients is more likely to be associated with the severity of underlying illness than with impaired cell-mediated immunity or HIV itself.
Trichosporonosis remains a difficult infection to treat because of its resistance to antifungal agents, including amphotericin B. Greater in-vitro efficacy of voriconazole over other antifungal agents for both T. asahii and non-asahii Trichosporon species has been reported .
Among HIV patients, T. asahii infection is associated with intravenous catheters rather than neutropenia, successful outcomes after timely catheter removal, and high mortality rates. Frequent hospitalization and antibiotic therapy may contribute to increasing the prevalence of resistant endogenous flora such as Trichosporon.
Conflicts of interest: None. The views expressed in this article are those of the authors and do not necessarily reflect the policies of the US Department of Veterans Affairs.
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