Wordell C J, Hauptman S P
Department of Pharmacy, Thomas Jefferson University Hospital, Philadelphia, PA 19107.
Clin Pharm. 1988 Jul;7(7):514-27.
A 44-year-old man with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) who suffered adverse effects from treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and was then treated with pentamidine isethionate is described, and approved and investigational drugs used in the management of PCP in the AIDS patient are discussed. After taking TMP-SMX, 240 mg trimethoprim and 1200 mg sulfamethoxazole, four times a day orally for 10 days at home, the patient was hospitalized complaining of nausea, vomiting, diarrhea, and fever. Intravenous TMP-SMX was begun at a dosage of 18 mg/kg/day of trimethoprim. Four days later, his condition had deteriorated and he had elevations of liver enzymes and a decrease in white blood cell (WBC) count. TMP-SMX was discontinued and pentamidine isethionate was started at a dosage of 4 mg/kg/day i.v. His symptoms and fever subsided and his liver enzyme levels and WBC count improved. After nine days of pentamidine his WBC count decreased; pentamidine was suspected as the cause and discontinued; no further therapy was needed. PCP was the initial infection that established this patient's diagnosis of AIDS. The patient did not have exertional dyspnea and nonproductive cough, which are usually seen in AIDS patients with PCP. TMP-SMX 20 mg/kg/day, based on the trimethoprim content, is the usual initial treatment for PCP. Adverse effects of TMP-SMX develop more frequently in AIDS patients than in non-AIDS patients with PCP. The recommended dose of pentamidine isethionate for the treatment of PCP is 4 mg/kg/day, im. or i.v. A few studies have shown good response to aerosolized pentamidine. Trials of investigational agents have excluded patients with severely compromised respiratory status; eflornithine, dapsone in combination with trimethoprim, and trimetrexate have been used. Corticosteroids should be considered a last effort until additional data are available. TMP-SMX may be used to prevent recurrence of PCP or to prevent the initial occurrence of PCP in AIDS patients. Intravenous or aerosol doses of pentamidine may be effective as prophylaxis. Sulfadoxine-pyrimethamine tried as prophylaxis produced adverse reactions. Despite its higher incidence of serious adverse effects in the AIDS population, TMP-SMX is considered preferable to pentamidine for initial therapy. Pentamidine is preferred for patients with documented allergy to TMP-SMX or failure to respond to a five- to seven-day course of TMP-SMX.
本文描述了一名44岁患有获得性免疫缺陷综合征(AIDS)和卡氏肺孢子虫肺炎(PCP)的男性患者,他在接受甲氧苄啶 - 磺胺甲恶唑(TMP - SMX)治疗时出现不良反应,随后接受了乙磺半胱氨酸戊烷脒治疗,并讨论了用于AIDS患者PCP管理的已批准和研究性药物。患者在家中口服TMP - SMX(甲氧苄啶240mg和磺胺甲恶唑1200mg,每日4次,共10天)后,因出现恶心、呕吐、腹泻和发热而住院。开始静脉注射TMP - SMX,剂量为甲氧苄啶18mg/kg/天。4天后,他的病情恶化,肝酶升高,白细胞(WBC)计数下降。停用TMP - SMX,开始静脉注射乙磺半胱氨酸戊烷脒,剂量为4mg/kg/天。他的症状和发热消退,肝酶水平和WBC计数改善。使用戊烷脒9天后,他的WBC计数下降;怀疑是戊烷脒所致,遂停药;无需进一步治疗。PCP是确立该患者AIDS诊断的初始感染。该患者没有通常在患有PCP的AIDS患者中出现的劳力性呼吸困难和干咳。基于甲氧苄啶含量,20mg/kg/天的TMP - SMX是PCP的常用初始治疗方法。与患有PCP的非AIDS患者相比,TMP - SMX的不良反应在AIDS患者中更频繁发生。治疗PCP推荐的乙磺半胱氨酸戊烷脒剂量为4mg/kg/天,肌肉注射或静脉注射。一些研究表明雾化戊烷脒有良好反应。研究性药物试验排除了呼吸功能严重受损的患者;已使用依氟鸟氨酸、氨苯砜与甲氧苄啶联合用药以及三甲曲沙。在获得更多数据之前,应将皮质类固醇视为最后的治疗手段。TMP - SMX可用于预防AIDS患者PCP的复发或初次发生。静脉注射或雾化剂量的戊烷脒可能作为预防有效。尝试用作预防的周效磺胺 - 乙胺嘧啶产生了不良反应。尽管在AIDS人群中严重不良反应的发生率较高,但TMP - SMX仍被认为是初始治疗优于戊烷脒。对于有记录表明对TMP - SMX过敏或对5至7天疗程的TMP - SMX无反应的患者,戊烷脒是首选。