Ioannidis J P, Cappelleri J C, Skolnik P R, Lau J, Sacks H S
Division of Geographic Medicine and Infectious Diseases, New England Medical Center Hospitals, Boston, Mass, USA.
Arch Intern Med. 1996 Jan 22;156(2):177-88.
Finding the optimal strategy for Pneumocystis carinii prophylaxis in patients with human immunodeficiency virus infection can be problematic. Several prophylactic regimens are available, but their relative efficacy and tolerance are not well understood.
A meta-analysis overviewed 35 randomized trials comparing different regimens for P carinii prophylaxis directly or with placebo. Analyses were based on intention-to-treat. On-treatment data were also analyzed when available.
Regardless of dose, sulfamethoxazole-trimethoprim was almost universally effective for patients who tolerated it. The risk of discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by 43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for 1 year (primary prophylaxis), seven fewer patients would develop P carinii pneumonia, but 17 more would have significant toxic reactions. Aerosolized pentamidine was well tolerated regardless of the dose used. Prophylaxis failures might be halved if the dose of aerosolized pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens.
Sulfamethoxazole-trimethoprim is the superior regimen, and low doses could improve tolerance without losing effectiveness for primary prophylaxis. Low doses of dapsone reduce toxic effects, but at the expense of some loss of efficacy. There are few data on the use of low-dose regimens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis.
为感染人类免疫缺陷病毒的患者找到预防卡氏肺孢子虫的最佳策略可能存在问题。有几种预防方案可供选择，但它们的相对疗效和耐受性尚不清楚。
一项荟萃分析综述了35项随机试验，这些试验直接比较了不同的卡氏肺孢子虫预防方案或与安慰剂进行比较。分析基于意向性治疗。如有可用数据，也对治疗期间的数据进行了分析。
无论剂量如何，复方磺胺甲恶唑对能耐受的患者几乎普遍有效。如果每周服用三次双倍剂量片剂而非每日服用，因副作用而停用复方磺胺甲恶唑的风险降低了43%（95%置信区间，30%至54%）。对于氨苯砜，在100名患者中，每日服用100毫克而非每周两次服用1年（一级预防），患卡氏肺孢子虫肺炎的患者将减少7例，但出现严重毒性反应的患者将增加17例。无论使用何种剂量，雾化戊烷脒的耐受性都很好。如果将雾化戊烷脒的剂量加倍，预防失败的情况可能会减半。与雾化戊烷脒相比，通过治疗期间分析，口服方案预防弓形虫病事件的比例为73%（95%置信区间，57%至82%），但通过意向性治疗仅为33%（95%置信区间，12%至50%）。不同方案之间在死亡率方面未显示出显著差异。
复方磺胺甲恶唑是更优的方案，低剂量可提高耐受性且不影响一级预防的有效性。低剂量氨苯砜可降低毒性作用，但会牺牲一些疗效。关于低剂量方案用于二级预防的数据很少。高剂量雾化戊烷脒可能会提高该方案的疗效。雾化戊烷脒不足以预防弓形虫病，提高口服方案耐受性的策略可能会增加预防弓形虫病的有效性。
