Hirschel B, Lazzarin A, Chopard P, Opravil M, Furrer H J, Rüttimann S, Vernazza P, Chave J P, Ancarani F, Gabriel V
Division of Infectious Diseases, Hôpital Cantonal Universitaire, Geneva, Switzerland.
N Engl J Med. 1991 Apr 18;324(16):1079-83. doi: 10.1056/NEJM199104183241602.
Current recommendations for prophylaxis of Pneumocystis carinii pneumonia (PCP) are based on data from patients who have had at least one episode of PCP (secondary prevention). We designed a study to determine the efficacy and side effects of inhaled pentamidine in the primary prevention of PCP.
Two hundred twenty-three patients sero-positive for human immunodeficiency virus (HIV) who had the acquired immunodeficiency syndrome (AIDS) but not PCP, who had advanced AIDS-related complex, or who had less than 0.2 x 10(9) CD4-positive lymphocytes per liter received either 300 mg of pentamidine isethionate or 300 mg of sodium isethionate every 28 days by inhaler. The proportion of patients surviving without PCP was analyzed with the log-rank test as a function of time spent in the trial, according to the intention to treat with either placebo or pentamidine.
The third of five planned interim analyses showed a significant difference in the occurrence of PCP, with 8 cases in pentamidine group and 23 in the placebo group (nominal P value = 0.0021). There were no deaths within 60 days of the diagnosis of PCP and no significant differences in survival between groups. Approximately 53 inhalations were needed to prevent one episode of pneumonia. Thirty-eight of 114 patients given pentamidine (33 percent) and 7 of 109 given placebo (6 percent) had moderate-to-severe coughing during inhalations (two-tailed P less than 0.00001), which caused 4 patients given pentamidine (3.5 percent) to discontinue taking it.
A dose of 300 mg of aerosolized pentamidine given every four weeks was well tolerated and 60 to 70 percent effective in preventing a first episode of PCP in patients with HIV infection.
目前针对卡氏肺孢子虫肺炎（PCP）预防的建议是基于至少有过一次PCP发作的患者的数据（二级预防）。我们设计了一项研究以确定吸入戊烷脒在PCP一级预防中的疗效和副作用。
223名血清学检测人类免疫缺陷病毒（HIV）呈阳性、患有获得性免疫缺陷综合征（AIDS）但未患PCP、患有晚期AIDS相关综合征或每升CD4阳性淋巴细胞少于0.2×10⁹的患者，通过吸入器每28天接受300毫克的乙磺酸盐戊烷脒或300毫克的乙磺酸钠。根据意向性分析，即按照使用安慰剂或戊烷脒进行治疗，采用对数秩检验分析未患PCP存活患者的比例与在试验中所花费时间的函数关系。
五项计划中的中期分析中的第三次分析显示，PCP的发生率存在显著差异，戊烷脒组有8例，安慰剂组有23例（名义P值 = 0.0021）。在PCP诊断后的60天内没有死亡病例，且两组之间的生存率没有显著差异。预防一次肺炎发作大约需要53次吸入。接受戊烷脒治疗的114名患者中有38名（33%），接受安慰剂治疗的109名患者中有7名（6%）在吸入过程中出现中度至重度咳嗽（双侧P值小于0.00001），这导致4名接受戊烷脒治疗的患者（3.5%）停药。
每四周给予300毫克雾化戊烷脒的剂量耐受性良好，在预防HIV感染患者首次发作PCP方面有60%至70%的有效性。
