Pierce M, Crampton S, Henry D, Heifets L, LaMarca A, Montecalvo M, Wormser G P, Jablonowski H, Jemsek J, Cynamon M, Yangco B G, Notario G, Craft J C
Vanderbilt University, Nashville, USA.
N Engl J Med. 1996 Aug 8;335(6):384-91. doi: 10.1056/NEJM199608083350603.
Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic.
We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months.
After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively).
In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.
播散性鸟分枝杆菌复合体感染是获得性免疫缺陷综合征（AIDS）晚期患者最常见的机会性感染。我们研究了大环内酯类抗生素克拉霉素预防性治疗的疗效和安全性。
我们在美国和欧洲对AIDS患者进行了一项关于克拉霉素的随机、安慰剂对照、双盲研究。入选标准包括鸟分枝杆菌复合体血培养阴性、卡诺夫斯基功能状态评分50分或更高、每立方毫米CD4细胞计数100个或更少以及预期寿命至少6个月。
首次中期分析后，研究停止。在分配到克拉霉素组的333例患者中，有19例（6%）发生鸟分枝杆菌复合体感染，而在分配到安慰剂组的334例患者中有53例（16%）发生感染（校正风险比为0.31；95%置信区间为0.18至0.53；P<0.001）。在约10个月的随访期内，克拉霉素组32%的患者死亡，安慰剂组41%的患者死亡（风险比为0.75；P=0.026）。在克拉霉素组，19例鸟分枝杆菌复合体感染患者中有11例的分离株对克拉霉素耐药。克拉霉素预防与味觉异常发生率增加（克拉霉素组为11%，安慰剂组为2%，P<0.001）和直肠疾病发生率增加（8%对3%，P = 0.007）相关；然而，两组中更严重不良事件的发生率相似（分别为7%和6%）。
在晚期AIDS患者中，预防性给予克拉霉素耐受性良好，可预防鸟分枝杆菌复合体感染并降低死亡率。
