Denning D W, Tucker R M, Hanson L H, Hamilton J R, Stevens D A
Department of Medicine, Santa Clara Valley Medical Center, San Jose, Calif.
Arch Intern Med. 1989 Oct;149(10):2301-8.
We studied the efficacy of itraconazole, a new oral triazole, in 33 patients (32 were immunocompromised) with cryptococcosis. Diagnoses included cryptococcal meningitis (24 patients), cryptococcemia (19 patients), cryptococcuria (4 patients), osteomyelitis (1 patient), pulmonary cryptococcosis (1 patient), and soft-tissue cryptococcosis (2 patients). Twenty-six patients had the acquired immunodeficiency syndrome, and 4 were transplant recipients. Therapy (200 mg two times per day) was monitored by clinical response, culture, and cryptococcal antigen testing. Cryptococcemia was abolished in 10 (100%) of 10 assessable patients; clinical abnormalities also cleared. Thirteen (65%) of 20 assessable patients with cryptococcal meningitis had complete responses (clinical resolution and negative cultures), 5 (25%) had partial responses, and therapy failed in 2 (10%). Ten (71%) of 14 patients with the acquired immunodeficiency syndrome who had meningitis and were treated with itraconazole as their sole therapy had complete responses, 3 (21%) had partial responses, and therapy failed in 1 (7%). Partial responses or failures were all associated with the failure of previous therapy, severe disease, low serum itraconazole concentrations, or a resistant organism. Noncompliance was associated with relapse (4 patients). Meningitis recrudesced in 3 (20%) of 15 patients who responded to therapy. All 4 patients with pulmonary cryptococcosis, soft-tissue cryptococcosis, or osteomyelitis responded to therapy (100%). Cryptococcuria was abolished in 3 (60%) of 5 assessable patients. The median survival of the 20 patients with the acquired immunodeficiency syndrome who had meningitis exceeded 10.5 months at this writing. Overall results compare favorably with amphotericin B therapy with or without flucytosine. Forty of 44 isolates of Cryptococcus neoformans were susceptible in vitro to itraconazole (minimum inhibitory concentration less than or equal to 3.13 mg/L), 3 were borderline (minimum inhibitory concentration, 6.25 mg/L), and 1 was resistant (minimum inhibitory concentration, 12.5 mg/L). As itraconazole does not penetrate cerebrospinal fluid, the meningitis results are noteworthy and suggest that meningeal and parenchymal penetration is critical. Itraconazole is promising for the treatment of cryptococcosis in patients with and without the acquired immunodeficiency syndrome.
我们研究了新型口服三唑类药物伊曲康唑对33例隐球菌病患者（32例免疫功能低下）的疗效。诊断包括隐球菌性脑膜炎（24例）、隐球菌血症（19例）、隐球菌尿症（4例）、骨髓炎（1例）、肺隐球菌病（1例）和软组织隐球菌病（2例）。26例患者患有获得性免疫缺陷综合征，4例为移植受者。通过临床反应、培养和隐球菌抗原检测来监测治疗（每日2次，每次200mg）。10例可评估患者中的10例（100%）隐球菌血症消失；临床异常也得以清除。20例可评估的隐球菌性脑膜炎患者中有13例（65%）获得完全缓解（临床症状消失且培养阴性），5例（25%）部分缓解，2例（10%）治疗失败。14例患有脑膜炎且仅接受伊曲康唑治疗的获得性免疫缺陷综合征患者中有10例（71%）获得完全缓解，3例（21%）部分缓解，1例（7%）治疗失败。部分缓解或治疗失败均与先前治疗失败、病情严重、血清伊曲康唑浓度低或存在耐药菌有关。不依从与复发相关（4例）。15例对治疗有反应的患者中有3例（20%）脑膜炎复发。所有4例肺隐球菌病、软组织隐球菌病或骨髓炎患者对治疗均有反应（100%）。5例可评估患者中有3例（60%）隐球菌尿症消失。撰写本文时，20例患有脑膜炎的获得性免疫缺陷综合征患者的中位生存期超过10.5个月。总体结果与两性霉素B联合或不联合氟胞嘧啶治疗相比具有优势。44株新型隐球菌分离株中有40株在体外对伊曲康唑敏感（最低抑菌浓度小于或等于3.13mg/L），3株为临界敏感（最低抑菌浓度为6.25mg/L），1株耐药（最低抑菌浓度为12.5mg/L）。由于伊曲康唑不能穿透脑脊液，脑膜炎的治疗结果值得关注，提示脑膜和实质的渗透至关重要。伊曲康唑在治疗有或无获得性免疫缺陷综合征的隐球菌病患者方面很有前景。
