一项关于氟康唑持续或间歇治疗HIV感染患者口腔念珠菌病的随机试验：临床结果及氟康唑耐药性的产生

A randomized trial of continuous or intermittent therapy with fluconazole for oropharyngeal candidiasis in HIV-infected patients: clinical outcomes and development of fluconazole resistance.

作者信息

Revankar S G, Kirkpatrick W R, McAtee R K, Dib O P, Fothergill A W, Redding S W, Rinaldi M G, Hilsenbeck S G, Patterson T F

机构信息

University of Texas Health Science Center, San Antonio 78284-7881, USA.

出版信息

Am J Med. 1998 Jul;105(1):7-11. doi: 10.1016/s0002-9343(98)00137-5.

DOI:10.1016/s0002-9343(98)00137-5

PMID:9688014

Abstract

PURPOSE

The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known.

PATIENTS AND METHODS

We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count <350 x 10(6)/L and oropharyngeal candidiasis in a prospective, randomized study. After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses. Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures. Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 microg/mL from the initial culture in the same species, the emergence of new, resistant (MIC > or =16 microg/mL) species, or a significant increase in the proportion of resistant isolates.

RESULTS

During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P <0.001). Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04). Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75). However, despite isolates with increased MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day.

CONCLUSIONS

In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization. Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent.

摘要

目的

氟康唑持续或间歇治疗对氟康唑耐药性的复发及产生的影响尚不清楚。

患者与方法

我们在一项前瞻性随机研究中，对CD4细胞计数<350×10⁶/L且患有口腔念珠菌病的人类免疫缺陷病毒（HIV）阳性患者进行了研究。初始治疗后，20例患者（其中16例完成了3个月的随访）接受每日200mg氟康唑的持续治疗，48例患者（其中28例完成了随访）在症状复发时接受间歇治疗。在感染发作期间每周采集口腔样本，作为监测培养每季度采集一次。耐药性的产生定义为同一菌种初始培养的最低抑菌浓度（MIC）至少升高四倍至16μg/mL以上、出现新的耐药菌种（MIC≥16μg/mL）或耐药菌株比例显著增加。

结果

在平均11个月的随访期间，持续治疗患者的年复发率中位数（每年0次发作）低于间歇治疗患者（每年4.1次发作；P<0.001）。持续治疗的16例患者中有6例（38%）培养结果无菌，而间歇治疗的28例患者中有3例（11%）培养结果无菌（P = 0.04）。持续治疗的16例患者中有9例（56%）出现微生物耐药，间歇治疗的28例患者中有13例（46%）出现微生物耐药（P = 0.75）。然而，尽管分离株的MIC有所增加，但44例患者中有42例对每日剂量高达800mg的氟康唑有反应。