Breakthrough fungemia caused by fluconazole-resistant Candida albicans with decreased susceptibility to voriconazole in patients with hematologic malignancies.

A 7-year retrospective analysis of candidemia in patients with hematologic malignancies demonstrated that ten patients, who received itraconazole and fluconazole during neutropenia, developed breakthrough fungemia caused by fluconazole-resistant Candida albicans (C. albicans) with decreased susceptibility to voriconazole. Eight of these ten patients died of candidemia despite amphotericin B administration. Karyotype analysis of C. albicans isolates revealed that all isolates were genetically unrelated? Our findings suggest that blood isolates of C. albicans in neutropenic patients receiving azoles could be azole cross-resistant, and that the patients should be treated by other antifungals such as echinocandins.

Clinical significance of breakthrough fungemia caused by azole-resistant Candida tropicalis in patients with hematologic malignancies.

A 5-year retrospective analysis of fungemia in patients with hematologic malignancies revealed that four patients, who received fluconazole and itraconazole during neutropenia, developed breakthrough candidemia due to azole-resistant Candida tropicalis isolates. This observation suggests that causative organisms of candidemia in neutropenic patients receiving azoles should be suspected of being azole-resistant.

Molecular epidemiology of invasive stomatitis due to Aspergillus flavus in patients with acute leukemia.

BACKGROUND: Invasive oral aspergillosis is a rare complication and only little information on the epidemiology of Aspergillus flavus infection is available. We present here the molecular analysis of the epidemiology of invasive stomatitis due to Aspergillus flavus in patients with acute leukemia. METHODS: During a 5-year period (1992-1996), six isolates of A. flavus were obtained from leukemic patients with invasive Aspergillus stomatitis. Random amplification of polymorphic DNA (RAPD) with three different PCR primers was carried out to investigate the DNA typing of the isolates. RESULTS: The molecular analysis using RAPD revealed that three isolates of A. flavus obtained in 1992 from three patients were of the same type, whereas each of the isolates from the other three patients had a distinct unique band, resulting in four groups of A. flavus. CONCLUSION: As the three patients with invasive oral aspergillosis detected in 1992 were infected by a single strain of A. flavus, the strain was suspected to have caused a nosocomial outbreak of invasive oral aspergillosis in the hematology unit.

Successful treatment of invasive stomatitis due to Exophiala dermatitidis in a patient with acute myeloid leukemia.

BACKGROUND: Although the most common orofacial fungal infection in immunocompromised patients is candidosis, infections caused by virulent molds, such as Aspergillus spp. and Furarium spp. are being recognized with increasing frequency. We report a case of oral Exophiala infection in a 39-year-old woman with acute myeloid leukemia. METHODS: Clinical records of the patient were reviewed and the following additional information was collected: histological and microbiological evidence; identification of the causative organism; in vitro antifungal susceptibility. RESULTS: The patient developed a necrotic ulcer surrounded by a violaceous rim in the gingiva during neutropenia. Exophiala dermatitidis was identified as the causative organism by histopathological examination and culture, and finally confirmed by sequencing of the ribosomal DNA internal transcribed space domain. In vitro, amphotericin B was found to show strong activity against the Exophiala isolate while itraconazole showed less activity. The patient was successfully treated with parenteral amphotericin B and oral itraconazole in combination with surgical removal of the fungi focus. CONCLUSION: Local excision with adequate antifungal agents can be used to treat immunocompromised patients with Exophiala stomatitis, based on early diagnosis.

Itraconazole prophylaxis for invasive gingival aspergillosis in neutropenic patients with acute leukemia.

BACKGROUND: Due to an increasing number of leukemic patients with invasive gingival aspergillosis during neutropenia (neutrophils <500 cells/microl for >10 days), we evaluated the efficacy of oral itraconazole prophylaxis for preventing this invasive infection at our hospital. METHODS: This was a retrospective, non-randomized study to analyze the onset of identified invasive gingival aspergillosis among 536 patients with acute leukemia at risk due to the presence of neutropenia from 1991 to 1998. Patients received itraconazole capsules 100 mg/day prophylactically between April 1994 and December 1996, and 200 mg/day between January 1997 and December 1998. Itraconazole serum levels at day 10 were measured in some patients. RESULTS: In the 39 months prior to April 1994 without itraconazole prophylaxis, 15 cases of invasive gingival aspergillosis were detected in 192 high risk patients with 469 episodes of neutropenia (7.8% of the high risk patients). Between April 1994 and December 1996, using itraconazole prophylaxis at 100 mg/day, there was a dramatic decrease in the infections resulting in 3 of 198 high risk patients with 511 episodes of neutropenia (1.5% of the high risk patients). Furthermore, between January 1997 and December 1998, using itraconazole prophylaxis at 200 mg/day, no cases of the infection were observed in the 146 high risk patients with 380 episodes of neutropenia. The incidence of invasive gingival aspergillosis was significantly lower among patients administered itraconazole than among those without itraconazole (100 mg/day; P = 0.006 and 200 mg/day; P = 0.001). The mean itraconazole serum level in 20 patients receiving 100 mg/day was 71.78 ng/mL and in 16 patients receiving 200 mg/day was 202.67 ng/ml. CONCLUSIONS: These findings suggest that oral itraconazole could be effective for preventing invasive gingival aspergillosis in neutropenic patients with acute leukemia and warrants further randomized investigation.