From the Department of Biostatistics, University of Washington Clinical Trial Center, Seattle (A.-S.G., R.S., J.H., S.M.); the University of North Carolina Project, Lilongwe Medical Relief Fund Trust, Tidziwe Centre (T.M., M.P., C.B.N.), and Acute Respiratory Infection and Emergency Triage Assessment and Treatment, Malawi Ministry of Health (N.L.), Lilongwe, and the Department of Pediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (A.P.) - all in Malawi; Save the Children, Fairfield, CT (E.N.); and Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins School of Medicine and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore (E.D.M.).
N Engl J Med. 2020 Jul 2;383(1):13-23. doi: 10.1056/NEJMoa1912400.
Evidence regarding the appropriate duration of treatment with antibiotic agents in children with pneumonia in low-resource settings in Africa is lacking.
We conducted a double-blind, randomized, controlled, noninferiority trial in Lilongwe, Malawi, to determine whether treatment with amoxicillin for 3 days is less effective than treatment for 5 days in children with chest-indrawing pneumonia (cough lasting <14 days or difficulty breathing, along with visible indrawing of the chest wall with or without fast breathing for age). Children not infected with human immunodeficiency virus (HIV) who were 2 to 59 months of age and had chest-indrawing pneumonia were randomly assigned to receive amoxicillin twice daily for either 3 days or 5 days. Children were followed for 14 days. The primary outcome was treatment failure by day 6; noninferiority of the 3-day regimen to the 5-day regimen would be shown if the percentage of children with treatment failure in the 3-day group was no more than 1.5 times that in the 5-day group. Prespecified secondary analyses included assessment of treatment failure or relapse by day 14.
From March 29, 2016, to April 1, 2019, a total of 3000 children underwent randomization: 1497 children were assigned to the 3-day group, and 1503 to the 5-day group. Among children with day 6 data available, treatment failure had occurred in 5.9% in the 3-day group (85 of 1442 children) and in 5.2% (75 of 1456) in the 5-day group (adjusted difference, 0.7 percentage points; 95% confidence interval [CI], -0.9 to 2.4) - a result that satisfied the criterion for noninferiority of the 3-day regimen to the 5-day regimen. Among children with day 14 data available, 176 of 1411 children (12.5%) in the 3-day group and 154 of 1429 (10.8%) in the 5-day group had had treatment failure by day 6 or relapse by day 14 (between-group difference, 1.7 percentage points; 95% CI, -0.7 to 4.1). The percentage of children with serious adverse events was similar in the two groups (9.8% in the 3-day group and 8.8% in the 5-day group).
In HIV-uninfected Malawian children, treatment with amoxicillin for chest-indrawing pneumonia for 3 days was noninferior to treatment for 5 days. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02678195.).
在非洲资源匮乏的环境中，针对儿童肺炎抗生素治疗时间的恰当长度，目前尚无相关证据。
我们在马拉维利隆圭进行了一项双盲、随机、对照、非劣效性试验，以确定对于存在吸气性胸凹陷（咳嗽持续时间<14 天或呼吸困难，同时伴有或不伴有与年龄相应的胸壁内陷性呼吸急促）的儿童，阿莫西林治疗 3 天是否不如治疗 5 天有效。年龄在 2 至 59 个月、未感染人类免疫缺陷病毒（HIV）且患有吸气性肺炎的儿童被随机分为两组，分别接受每日两次阿莫西林治疗 3 天或 5 天。儿童接受为期 14 天的随访。主要结局是第 6 天的治疗失败；如果 3 天组的治疗失败比例不超过 5 天组的 1.5 倍，则表明 3 天方案不劣于 5 天方案。预先设定的次要分析包括第 14 天评估治疗失败或复发。
2016 年 3 月 29 日至 2019 年 4 月 1 日，共有 3000 名儿童接受了随机分组：1497 名儿童被分配到 3 天组，1503 名儿童被分配到 5 天组。在第 6 天有数据可用的儿童中，3 天组的治疗失败率为 5.9%（1442 名儿童中有 85 名），5 天组为 5.2%（1456 名儿童中有 75 名）（调整差异，0.7 个百分点；95%置信区间[CI]，-0.9 至 2.4）-结果符合 3 天方案不劣于 5 天方案的标准。在第 14 天有数据可用的儿童中，3 天组有 176 名（12.5%）儿童和 5 天组有 154 名（10.8%）儿童在第 6 天或第 14 天出现治疗失败或复发（组间差异，1.7 个百分点；95%CI，-0.7 至 4.1）。两组儿童严重不良事件的发生率相似（3 天组为 9.8%，5 天组为 8.8%）。
在未感染 HIV 的马拉维儿童中，阿莫西林治疗吸气性肺炎 3 天与 5 天的疗效相当。（由比尔和梅琳达盖茨基金会资助；临床试验.gov 编号，NCT02678195）。
