Disseminated Infection with Prototheca zopfii after Unrelated Stem Cell Transplantation for Leukemia

Abstract

Disseminated infection with Prototheca zopfii is a rare disease in immunosuppressed patients. We here report the first case of lethal infection with P. zopfii following unrelated stem cell transplantation for leukemia. Breakthrough protothecosis occurred during long-term administration of voriconazole in the case of pulmonary aspergillosis. CASE REPORTA 58-year-old man was diagnosed with osteomyelofibrosis in 1998. Four years later, the patient developed chemotherapyrefractory secondary acute leukemia (FAB-M1), and a oneantigen mismatched bone marrow transplantation from an unrelated donor was performed after reduced-intensity conditioning despite proven aspergillosis. Pulmonary aspergillosis was controlled by administering voriconazole (Pfizer, Vienna, Austria) in combination with caspofungin (MSD, Vienna, Austria) during the neutropenic period. Antifungal maintenance therapy consisted of monotherapy with voriconazole (400 mg/day). Three months later, leukemic relapse occurred while the patient was still under immunosuppression with cyclosporine. After immunosuppression was discontinued, reinduction with fludarabine, high-dose cytarabine, and granulocyte colony-stimulating factor was started but without success. The patient's refractory leukemia was treated with gemtuzumab ozogamicin (Mylotarg; Wyeth, Vienna, Austria) in order to induce remission for subsequent donor lymphocyte infusion since no graft-versus-host disease had yet been diagnosed. During severe pancytopenia after gemtuzumab ozogamicin the patient developed fever of up to 41°C, which was unresponsive to ceftazidime, vancomycin, and netilmicin. Concurrently, spotted pulmonary infiltrates were visible in a computerized tomography scan, raising suspicion of aspergillosis reactivation. Antifungal therapy was extended to caspofungin. At that time, erythematous skin papules appeared on the upper extremities and spread rapidly over the whole body. Multiple blood cultures with aerobic, anaerobic, and fungal broths were taken and incubated in a BACTEC 9050 blood culture system (Becton Dickinson, Cockeysville, Md.).After 3 days of incubation at 37°C yeast-like fungi were grown on Sabouraud dextrose agar (Merck, Vienna, Austria) from several blood cultures. Prototheca zopfii was identified with Vitek 2 (bioMerieux, Marcy l'Etoile, France) and confirmed with the RapID Yeast Plus (code 730010) system (Remel, Santa Fe, N.Mex.) and microscopic examination. Cornmeal agar showed typical findings for P. zopfii: small spherules in aggregates with multiple internal cleavage. Susceptibility testing was performed by E-test as described by the manufacturer (AB Biodisk, Solna, Sweden). The medium consisted of RPMI 1640 agar with 2% glucose; the inoculum suspension was adjusted to the turbidity of a 0.5 McFarland standard and incubated at 37°C for 48 h. In vitro susceptibility gave the following MICs: amphotericin B, 0.125 g/ml; voriconazole, Ͼ64 g/ml. These results correlated with the MICs obtained with the National Committee for Clinical Laboratory Standards reference br...

Human Protothecosis

“…Also, rare cases of onychoprotothecosis have been described (47,168). Endogenous infections may arise in colonized patients with predisposing factors (65,78,148,150).…”

“…Of all the immunosuppressive drugs prescribed, glucocorticoids are the most widely used and the most specifically associated with the onset of Prototheca infection. Infection has resulted, e.g., from locally injected steroids (66,80,109), systemic steroids (78,109,152), oral steroids (12), and even the application of topical steroid cream (45). Infection has also resulted in diseases that are themselves treated with steroids, e.g., lupus erythematosus (147), lymphoma (53), rheumatoid arthritis (27,100), and myasthenia gravis (92).…”

“…Cases have been reported from Europe (61,77,78,93,129), Asia (28,85,86,96,145,147,169), Africa (36), Oceania (55), and South and North America (45,90,166,167), particularly the southeast United States (45,55,158,166). In Taiwan, the rural region is most affected, displaying a high population of farmers and elderly people (27).…”

“…Uncommon presentations, such as urinary tract protothecosis (156), colpitis (61), respiratory tract protothecosis (56), choroiditis (51), intestinal protothecosis (125), ungual infections (47,168), and meningitis (62,144), have been documented in the literature. Also, three cases with lung involvement have been reported, including one case of probable and two cases of autopsy-proven pulmonary infection (78,150).…”

Detection and Identification of Genotypes of <i>Prototheca zopfii</i> in Clinical Samples by Quantitative PCR Analysis

“…zopfii reportedly causes refractory subcutaneous diseases and systemic infections in humans (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). In animals, it causes various types of infections, which are sometimes fatal (6).…”