Bozzette S A, Larsen R A, Chiu J, Leal M A, Jacobsen J, Rothman P, Robinson P, Gilbert G, McCutchan J A, Tilles J
Division of Infectious Diseases, Univeristy of California, San Diego.
N Engl J Med. 1991 Feb 28;324(9):580-4. doi: 10.1056/NEJM199102283240902.
In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase.
Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups.
In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.
在获得性免疫缺陷综合征（AIDS）患者中，隐球菌性脑膜炎初次治疗后的复发率仍然很高。我们进行了一项对照双盲试验，以评估氟康唑维持治疗的疗效。在进入研究时，所有参与者在接受标准化的培养确诊隐球菌性脑膜炎治疗疗程后，脑脊液、血液和尿液培养均无菌。患者被随机分配接受氟康唑或安慰剂作为维持治疗。在研究的第一阶段，氟康唑的剂量为每日100毫克，第二阶段为每日200毫克。
最初入组的84例患者中，16例（19%）在进入研究后培养结果呈阳性，被发现存在无症状的持续性感染；另外7例患者在入组后不久失访。在其余61例患者中，27例分配到安慰剂组的患者中有10例（37%），34例分配到氟康唑组的患者中有1例（3%）在任何部位出现隐球菌感染复发（风险差异为34%；95%置信区间为15%至53%）。在11例复发性感染中，7例在前列腺按摩后获得的尿液中检测到。接受安慰剂治疗的患者中有4例复发性脑膜感染，而接受氟康唑治疗的患者中无复发性脑膜感染（平均随访时间为164天）（P = 0.03）。在多变量分析中，无复发生存的最佳预测因素是氟康唑治疗（P = 0.02；相对风险为13.2）、较低的血清隐球菌抗原滴度（P = 0.05；相对风险为1.2）以及更长时间的氟胞嘧啶初始治疗（P = 0.09；相对风险为1.1）。两个维持治疗组的生存率和毒性相似。
在AIDS患者中，隐球菌性脑膜炎临床治疗成功后，无症状的持续性感染很常见。氟康唑维持治疗在预防隐球菌感染复发方面非常有效。
