Hughes W, Leoung G, Kramer F, Bozzette S A, Safrin S, Frame P, Clumeck N, Masur H, Lancaster D, Chan C
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tenn. 38105.
N Engl J Med. 1993 May 27;328(21):1521-7. doi: 10.1056/NEJM199305273282103.
Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii.
We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg).
Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group.
For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.
甲氧苄啶 - 磺胺甲恶唑和喷他脒都是治疗卡氏肺孢子虫肺炎的有效药物，但不良反应常常限制它们的使用。阿托伐醌（566C80）是一种新型的羟基萘醌，对卡氏肺孢子虫具有活性。
我们对获得性免疫缺陷综合征合并轻度或中度严重卡氏肺孢子虫肺炎的患者进行了一项双盲、多中心研究。他们被随机分配，每日三次口服给药，持续21天，分别给予阿托伐醌（750毫克）或甲氧苄啶（320毫克）加磺胺甲恶唑（1600毫克）。
在322例经组织学确诊为卡氏肺孢子虫肺炎的患者中，160例接受阿托伐醌治疗，162例接受甲氧苄啶 - 磺胺甲恶唑治疗。在可评估治疗效果的患者中，接受阿托伐醌治疗的138例患者中有28例（20%）无反应，接受甲氧苄啶 - 磺胺甲恶唑治疗的146例患者中有10例（7%）无反应（P = 0.002）。阿托伐醌组有11例患者（7%）因治疗受限的不良反应需要更换治疗方案，甲氧苄啶 - 磺胺甲恶唑组有33例患者（20%）需要更换（P = 0.001）。仅使用初始药物治疗成功且无不良反应的患者，阿托伐醌组占62%，甲氧苄啶 - 磺胺甲恶唑组占64%。在治疗结束后的四周内，阿托伐醌组有11例死亡（4例死于卡氏肺孢子虫肺炎），甲氧苄啶 - 磺胺甲恶唑组有1例死亡（P = 0.003）。阿托伐醌组治疗开始时出现腹泻与较低的血浆药物浓度（P = 0.009）、治疗失败（P < 0.001）和死亡（P < 0.001）相关，但在甲氧苄啶 - 磺胺甲恶唑组中无此关联。
对于卡氏肺孢子虫肺炎的治疗，阿托伐醌的疗效不如甲氧苄啶 - 磺胺甲恶唑，但它的治疗受限不良反应较少。
