Infection due to non-Aspergillus fungi in immunocompromised patients receiving itraconazole.

Sir—Chariyalertsak et al. [1] recently reported the efficacy of oral itraconazole prophylaxis for prevention of systemic fungal infections (particularly cryptococcosis and penicilliosis) in patients with advanced HIV infection included in a controlled trial. We also previously reported that oral itraconazole was effective for the prevention of invasive orofacial aspergillosis in neutropenic patients with acute leukemia [2]. At the Hiroshima Red Cross and Atomic Bomb Survivors Hospital, orofacial aspergillosis has not been seen in immunocompromised patients since itraconazole prophylaxis began to be routinely administered to such patients in 1997. However, we recently saw 3 patients with invasive orofacial infections caused by non-Aspergillus fungi that had high itraconazole MICs on in vitro susceptibility testing. The first patient was a 39-year-old woman with acute myelogenous leukemia who developed invasive stomatitis due to Exophiala dermatitidis in January 1999. The patient was successfully treated a combination of surgery and parenteral administration of amphotericin B. The second patient was a 66-year-old woman with malignant lymphoma who developed hemimaxillary necrosis due to Trichoderma longibrachiatum in June 1999. The infection rapidly disseminated to the lungs, and the patient died, despite receiving intensive parenteral amphotericin B treatment. The third patient was a 29year-old man with severe aplastic anemia who developed oroantral infection due to Mucor racemosus in December 2000. The infection was successfully managed with a combination of surgery and parenteral amphotericin B. All patients received itraconazole capsules (200 mg/day) as antifungal prophylaxis for 27–40 days before a diagnosis of invasive fungal infection was made on the basis of clinicohistological and microbiological evidence. All causative organisms were finally identified by sequencing of the rDNA internal transcribed domain. In vitro susceptibility studies revealed that the causative organisms in these 3 cases had itraconazole MICs that were higher than those for isolates from oral Aspergillus infections, for which the range is 0.125–0.25 mg/mL (table 1) [3]. All causative fungi isolated from samples from our patients were susceptible to amphotericin B. These results suggest that fungi with low susceptibility to itraconazole were present in the environment and might have colonized patients, resulting in the development of invasive orofacial infections while the patients were receiving itraconazole as antifungal prophylaxis. Chariyalertsak et al. [1] described a case of penicilliosis in the group of patients in that study who were receiving itraconazole prophylaxis, but the in vitro susceptibility data for the causative fungi were not clear; such data are needed if infections are to be treated effectively. In conclusion, it should be noted that invasive fungal infections that develop in severely immunocompromised patients who do not respond to itraconazole prophylaxis need to be managed with intensive antifungal treatment with other effective drugs, such as amphotericin B, that should be selected on the basis of the results of in vitro susceptibility testing.