Disseminated Infection Due to Chrysosporium zonatum in a Patient with Chronic Granulomatous Disease and Review of Non-Aspergillus Fungal Infections in Patients with This Disease

We report the first case of Chrysosporium zonatum infection in a 15-year-old male with chronic granulomatous disease who developed a lobar pneumonia and tibia osteomyelitis while on prophylaxis with gamma interferon. The fungus was isolated from sputum and affected bone, and hyphae were observed in the bone by histopathology. Therapy with amphotericin B eradicated the osteomyelitis and pneumonia, but pneumonia recurred in association with pericarditis and pleuritis during therapy with itraconazole. These manifestations subsided, and no recurrences occurred with liposomal amphotericin B therapy. Infections caused by Chrysosporium species are very rare, and C. zonatum has not previously been reported to cause mycosis in humans. This species, the anamorph of the heterothallic ascomycete Uncinocarpus orissi (family Onygenaceae), is distinguished by its thermotolerance, by colonies which darken from yellowish white to buff, and by club-shaped terminal aleurioconidia borne at the ends of short, typically curved stalks. The case isolate produced fertile ascomata in mating tests with representative isolates. The median (range) MICs for our isolate as well as those for two other human isolates and a nonhuman isolate determined by the National Committee for Clinical Laboratory Standards method adapted for moulds were ≤0.06 μg/ml (≤0.06 to 0.25 μg/ml) for amphotericin B, 0.687 μg/ml (0.25 to 2 μg/ml) for itraconazole, >128 μg/ml (>128 μg/ml) for flucytosine, and 48 μg/ml (32 to >128 μg/ml) for fluconazole.

我们报告了首例发生于15岁慢性肉芽肿病（chronic granulomatous disease）男性患者的环带金孢霉（Chrysosporium zonatum）感染病例：该患者在接受γ干扰素（gamma interferon）预防治疗期间，并发大叶性肺炎（lobar pneumonia）与胫骨骨髓炎（tibia osteomyelitis）。该真菌从患者痰液（sputum）与受感染病灶骨骼中分离得到，且经组织病理学（histopathology）检测观察到骨骼组织内存在菌丝。采用两性霉素B（amphotericin B）治疗可根除骨髓炎与肺炎，但在伊曲康唑（itraconazole）治疗期间，肺炎复发并伴随心包炎（pericarditis）与胸膜炎（pleuritis）。上述症状随治疗逐步消退，且采用脂质体两性霉素B（liposomal amphotericin B）治疗后未再出现复发情况。金孢霉属（Chrysosporium）引发的感染极为罕见，此前尚无环带金孢霉导致人类真菌病（mycosis）的报道。该物种是异核子囊菌（heterothallic ascomycete）奥氏钩囊壳（Uncinocarpus orissi，爪甲团囊菌科Onygenaceae）的无性型（anamorph），其分类特征包括耐热性（thermotolerance）、菌落颜色由淡黄白色逐渐变为浅黄褐色，以及在短小且通常呈弯曲的柄端生有棒状端生侧生分生孢子（aleurioconidia）。本病例分离株在与代表性分离株进行的交配试验中，成功产生了可育子囊果。经适配于霉菌检测的美国临床实验室标准化委员会（National Committee for Clinical Laboratory Standards）方法测定，本病例分离株以及另外两株人类分离株与一株非人类分离株的最低抑菌浓度（MIC）如下：两性霉素B≤0.06 μg/ml（范围≤0.06~0.25 μg/ml），伊曲康唑0.687 μg/ml（范围0.25~2 μg/ml），氟胞嘧啶（flucytosine）>128 μg/ml（范围>128 μg/ml），氟康唑（fluconazole）48 μg/ml（范围32~>128 μg/ml）。