Fisher R G, Nageswaran S, Valentine M E, McKinney R E
Department of Pediatrics, Eastern Virginia Medical School, Norfolk, USA.
AIDS Patient Care STDS. 2001 May;15(5):263-9. doi: 10.1089/10872910152050784.
Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential part of the management of children with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). No dose-ranging studies were ever performed; therefore, the amount of trimethoprim-sulfamethoxazole (TMP-SMX) needed to suppress PCP in children with HIV/AIDS is not known. The dose recommended by the Centers for Disease Control (CDC) has been thought to be just above the threshold needed for prevention, based on anecdotal breakthrough PCP in cancer patients who were improperly dosed. We have been giving prophylaxis based on body weight rather than surface area, and this, combined with growth of our children, has led to a large experience with dosages lower than the currently recommended 150 mg/m2. The medical records of children with HIV who met CDC guidelines for institution of PCP prophylaxis were reviewed. To ascertain the per square meter (m2) dosage each child was receiving, body surface area was calculated from height and weight measurements. Dosages were recalculated every 6 months and at each dosage change. Data regarding PCP infection, bacterial infections, and side effects of TMP-SMX were extracted. Data were compiled from 1,719.5 child-months of TMP-SMX prophylaxis, including 1,532.5 child-months below the currently recommended dose. Sixty-seven percent of our child-months were at or below two-thirds the CDC recommended dose. There were no cases of proven or suspected PCP. Incidence of other serious bacterial infections was low. Bacteremia and sepsis with Streptococcus pneumoniae was the most common proven bacterial infection, at a rate of 5.5 episodes per 100 child-years. The incidence of bacterial infection did not vary by the dose of TMP-SMX. TMP-SMX prophylaxis was well tolerated; most reactions were mild and self-limited and did not recur with re-institution of the drug. Only 6.1% of this cohort had TMP-SMX prophylaxis discontinued due to perceived toxicity. These data show that the currently recommended dose of TMP-SMX (150 mg/m2) may not be required to prevent PCP in children with HIV/AIDS. The drug is well tolerated at all dosage levels. The incidence of serious bacterial infection in this cohort of patients did not depend upon the amount of TMP-SMX prescribed. A prospective, controlled clinical trial of low-dose TMP-SMX for children with HIV infection is warranted.
预防卡氏肺孢子虫肺炎（PCP）是人类免疫缺陷病毒（HIV）感染及获得性免疫缺陷综合征（AIDS）患儿治疗的重要组成部分。此前从未进行过剂量范围研究；因此，尚不清楚抑制HIV/AIDS患儿PCP所需的甲氧苄啶-磺胺甲恶唑（TMP-SMX）剂量。基于癌症患者因用药不当出现PCP突破性感染的传闻，疾病控制中心（CDC）推荐的剂量被认为略高于预防所需的阈值。我们一直根据体重而非体表面积给予预防用药，再加上患儿的生长发育，使得我们积累了大量低于目前推荐的150mg/m²剂量的用药经验。对符合CDC预防PCP指南的HIV患儿的病历进行了回顾。为确定每个患儿接受的每平方米（m²）剂量，根据身高和体重测量值计算体表面积。每6个月及每次剂量改变时重新计算剂量。提取了有关PCP感染、细菌感染及TMP-SMX副作用的数据。数据来自1719.5个患儿月的TMP-SMX预防用药，其中包括1532.5个低于目前推荐剂量的患儿月。我们67%的患儿月处于或低于CDC推荐剂量的三分之二。未出现确诊或疑似PCP病例。其他严重细菌感染的发生率较低。肺炎链球菌引起的菌血症和败血症是最常见的确证细菌感染，发生率为每100患儿年5.5例。细菌感染的发生率并不随TMP-SMX剂量的变化而改变。TMP-SMX预防用药耐受性良好；大多数反应轻微且为自限性，再次用药时未复发。该队列中仅6.1%的患儿因认为有毒性而停用TMP-SMX预防用药。这些数据表明，预防HIV/AIDS患儿的PCP可能无需目前推荐的TMP-SMX剂量（150mg/m²）。该药物在所有剂量水平下耐受性良好。该队列患者中严重细菌感染的发生率并不取决于所开具的TMP-SMX剂量。有必要对HIV感染患儿进行低剂量TMP-SMX的前瞻性对照临床试验。
