Baily G G, Perry F M, Denning D W, Mandal B K
Department of Infectious Diseases and Tropical Medicine (Monsall Unit), North Manchester General Hospital, University of Manchester School of Medicine, UK.
AIDS. 1994 Jun;8(6):787-92. doi: 10.1097/00002030-199406000-00010.
To report the occurrence of HIV-related mucosal candidosis that fails to respond to fluconazole, to establish the correlation between in vitro susceptibility testing and clinical failure, and to assess the efficacy of alternative treatments.
Chart review of all patients with fluconazole failure and all patients with CD4 counts < 50 x 10(6)/l continuing to respond to fluconazole, and prospective in vitro susceptibility testing of Candida.
A regional treatment centre for HIV-infected individuals in north-west England.
A cohort of 155 HIV-positive individuals with CD4 counts < 300 x 10(6)/l cells.
Clinical fluconazole failure was defined as symptomatic oropharyngeal or oesophageal candidosis despite fluconazole > or = 100 mg per day for 10 days. In vitro susceptibility to fluconazole was determined for Candida isolates. Cumulative 12-month fluconazole dose and time from first fluconazole therapy and prophylaxis were recorded.
Nine (5.8%) patients meeting the definition of fluconazole failure were identified. In vitro susceptibility to fluconazole of temporally related oropharyngeal isolates was reduced in all cases. Intravenous amphotericin B was the only effective treatment for these patients when symptoms were severe suggesting azole cross-resistance. One patient, who had received alternative treatments for 9 months, reverted from in vitro and clinical fluconazole sensitivity but relapsed within 6 weeks of resuming fluconazole. The median fluconazole dose over the preceding 12 months for the eight adult cases was 386 mg weekly. The median dose for the same period was 79 mg weekly in 28 patients with CD4 counts < 50 x 10(6)/l but without fluconazole failure (difference, 307; 95% confidence interval, 199-514; P < 0.0001).
A substantial problem of clinical fluconazole failure has developed among HIV-positive patients who have recurrent problematic mucosal candidosis.
报告对氟康唑无反应的HIV相关黏膜念珠菌病的发生情况，确立体外药敏试验与临床治疗失败之间的相关性，并评估替代治疗的疗效。
对所有氟康唑治疗失败的患者以及所有CD4细胞计数<50×10⁶/l且仍对氟康唑有反应的患者进行病历回顾，并对念珠菌进行前瞻性体外药敏试验。
英格兰西北部一家针对HIV感染者的地区治疗中心。
155名CD4细胞计数<300×10⁶/l的HIV阳性个体队列。
临床氟康唑治疗失败定义为尽管每天服用氟康唑≥100mg，持续10天，但仍出现有症状的口咽或食管念珠菌病。测定念珠菌分离株对氟康唑的体外敏感性。记录累积12个月的氟康唑剂量以及首次氟康唑治疗和预防后的时间。
确定了9名（5.8%）符合氟康唑治疗失败定义的患者。所有病例中，与时间相关的口咽分离株对氟康唑的体外敏感性均降低。当症状严重提示唑类交叉耐药时，静脉注射两性霉素B是这些患者唯一有效的治疗方法。一名接受替代治疗9个月的患者，从体外和临床氟康唑敏感状态转变，但在恢复氟康唑治疗后6周内复发。8例成年病例在之前12个月的氟康唑中位剂量为每周386mg。28例CD4细胞计数<50×10⁶/l但无氟康唑治疗失败的患者同期中位剂量为每周79mg（差异为307；95%置信区间为199 - 514；P<0.0001）。
在有复发性黏膜念珠菌病问题的HIV阳性患者中，已出现临床氟康唑治疗失败这一严重问题。
