Medina I, Mills J, Leoung G, Hopewell P C, Lee B, Modin G, Benowitz N, Wofsy C B
Medical Service, San Francisco General Hospital, CA 94110.
N Engl J Med. 1990 Sep 20;323(12):776-82. doi: 10.1056/NEJM199009203231202.
Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic.
In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day).
The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone.
In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.
获得性免疫缺陷综合征（AIDS）患者治疗卡氏肺孢子虫肺炎需要可口服的抗菌药物。初步数据表明，氨苯砜与甲氧苄啶联合使用可能是毒性常见的复方新诺明的有效替代药物。
在一项双盲试验中，60例患有AIDS且首次发生轻至中度卡氏肺孢子虫肺炎（在呼吸室内空气时动脉血氧分压大于60 mmHg）的患者被随机分配接受21天的治疗，一组接受复方新诺明治疗（分别为每日每千克体重20 mg和100 mg），另一组接受甲氧苄啶 - 氨苯砜治疗（每日每千克体重20 mg和每日100 mg）。
在接受复方新诺明治疗的30例患者中有3例、接受甲氧苄啶 - 氨苯砜治疗的30例患者中有2例因进行性肺炎导致口服治疗失败（P>0.3）。复方新诺明组有17例患者（57%）因严重毒性反应需要改用静脉注射喷他脒，而甲氧苄啶 - 氨苯砜组为9例（30%）（P<0.025）。使用复方新诺明时，严重化学性肝炎的病例更多（6例，而甲氧苄啶 - 氨苯砜组为1例），明显的中性粒细胞减少也更多（5例对1例）。两种药物组合出现难以耐受的皮疹（每组3例）和严重恶心呕吐（每组2例）的频率相同。大多数接受甲氧苄啶 - 氨苯砜治疗的患者发生了高铁血红蛋白血症，但均无症状，仅1例患者的水平超过20%。53%接受甲氧苄啶 - 氨苯砜治疗的患者还出现了轻度高钾血症（血清钾水平为5.1至6.1 mmol/L）。
对于AIDS患者轻至中度首次发作的卡氏肺孢子虫肺炎，复方新诺明和甲氧苄啶 - 氨苯砜的口服治疗同样有效，但甲氧苄啶 - 氨苯砜引起的严重不良反应比复方新诺明少。
