BACKGROUND Antibiotic resistance is a global public health issue, particularly in low- and middle-income countries (LMICs), where antibiotics required to treat resistant infections are not affordable. LMICs also bear a disproportionately high burden of bacterial diseases, particularly among children, and resistance jeopardizes progress made in these areas. Although outpatient antibiotic use is a major driver of antibiotic resistance, data on inappropriate antibiotic prescribing in LMICs are scarce at the community level, where the majority of prescribing occurs. Here, we aimed to characterize inappropriate antibiotic prescribing among young outpatient children and to identify its determinants in 3 LMICs. METHODS AND FINDINGS We used data from a prospective, community-based mother-and-child cohort (BIRDY, 2012 to 2018) conducted across urban and rural sites in Madagascar, Senegal, and Cambodia. Children were included at birth and followed-up for 3 to 24 months. Data from all outpatient consultations and antibiotics prescriptions were recorded. We defined inappropriate prescriptions as antibiotics prescribed for a health event determined not to require antibiotic therapy (antibiotic duration, dosage, and formulation were not considered). Antibiotic appropriateness was determined a posteriori using a classification algorithm developed according to international clinical guidelines. We used mixed logistic analyses to investigate risk factors for antibiotic prescription during consultations in which children were determined not to require antibiotics. Among the 2,719 children included in this analysis, there were 11,762 outpatient consultations over the follow-up period, of which 3,448 resulted in antibiotic prescription. Overall, 76.5% of consultations resulting in antibiotic prescription were determined not to require antibiotics, ranging from 71.5% in Madagascar to 83.3% in Cambodia. Among the 10,416 consultations (88.6%) determined not to require antibiotic therapy, 25.3% (n = 2,639) nonetheless resulted in antibiotic prescription. This proportion was much lower in Madagascar (15.6%) than in Cambodia (57.0%) or Senegal (57.2%) (p < 0.001). Among the consultations determined not to require antibiotics, in both Cambodia and Madagascar the diagnoses accounting for the greatest absolute share of inappropriate prescribing were rhinopharyngitis (59.0% of associated consultations in Cambodia, 7.9% in Madagascar) and gastroenteritis without evidence of blood in the stool (61.6% and 24.6%, respectively). In Senegal, uncomplicated bronchiolitis accounted for the greatest number of inappropriate prescriptions (84.4% of associated consultations). Across all inappropriate prescriptions, the most frequently prescribed antibiotic was amoxicillin in Cambodia and Madagascar (42.1% and 29.2%, respectively) and cefixime in Senegal (31.2%). Covariates associated with an increased risk of inappropriate prescription include patient age greater than 3 months (adjusted odds ratios (aOR) with 95% confidence interval (95% CI) ranged across countries from 1.91 [1.63, 2.25] to 5.25 [3.85, 7.15], p < 0.001) and living in rural as opposed to urban settings (aOR ranged across countries from 1.83 [1.57, 2.14] to 4.40 [2.34, 8.28], p < 0.001). Diagnosis with a higher severity score was also associated with an increased risk of inappropriate prescription (aOR = 2.00 [1.75, 2.30] for moderately severe, 3.10 [2.47, 3.91] for most severe, p < 0.001), as was consultation during the rainy season (aOR = 1.32 [1.19, 1.47], p < 0.001). The main limitation of our study is the lack of bacteriological documentation, which may have resulted in some diagnosis misclassification and possible overestimation of inappropriate antibiotic prescription. CONCLUSION In this study, we observed extensive inappropriate antibiotic prescribing among pediatric outpatients in Madagascar, Senegal, and Cambodia. Despite great intercountry heterogeneity in prescribing practices, we identified common risk factors for inappropriate prescription. This underscores the importance of implementing local programs to optimize antibiotic prescribing at the community level in LMICs.

中文翻译：

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3 个低收入和中等收入国家门诊儿童的抗生素处方不当及其决定因素：一项基于社区的多中心队列研究。

背景抗生素耐药性是一个全球性的公共卫生问题，特别是在低收入和中等收入国家 (LMIC)，在这些国家，治疗耐药性感染所需的抗生素负担不起。中低收入国家还承受着不成比例的细菌性疾病负担，尤其是在儿童中，耐药性会危及这些领域取得的进展。尽管门诊抗生素的使用是抗生素耐药性的主要驱动因素，但在大多数处方发生的社区层面，关于 LMIC 不当抗生素处方的数据很少。在这里，我们旨在描述年幼门诊儿童中不适当的抗生素处方的特征，并确定其在 3 个 LMIC 中的决定因素。方法和结果 我们使用了来自前瞻性、基于社区的母婴队列（BIRDY，2012 年至 2018 年）在马达加斯加、塞内加尔和柬埔寨的城市和农村地点进行。儿童在出生时就被纳入，并随访 3 至 24 个月。记录所有门诊咨询和抗生素处方的数据。我们将不适当的处方定义为为确定不需要抗生素治疗的健康事件开出的抗生素（未考虑抗生素持续时间、剂量和配方）。使用根据国际临床指南开发的分类算法事后确定抗生素的适用性。我们使用混合逻辑分析来调查在确定儿童不需要抗生素的咨询期间抗生素处方的风险因素。在本次分析的 2,719 名儿童中，有 11 名，随访期间门诊就诊 762 人，其中 3,448 人开抗生素处方。总体而言，76.5% 的抗生素处方咨询被确定为不需要抗生素，从马达加斯加的 71.5% 到柬埔寨的 83.3% 不等。在确定不需要抗生素治疗的 10,416 次咨询 (88.6%) 中，25.3% (n = 2,639) 仍然开出了抗生素处方。马达加斯加的这一比例 (15.6%) 远低于柬埔寨 (57.0%) 或塞内加尔 (57.2%) (p < 0.001)。在确定不需要抗生素的咨询中，在柬埔寨和马达加斯加，占不适当处方的最大绝对份额的诊断是鼻咽炎（柬埔寨相关咨询的 59.0%，7. 9% 在马达加斯加）和没有便血证据的肠胃炎（分别为 61.6% 和 24.6%）。在塞内加尔，无并发症的毛细支气管炎占不当处方数量最多（占相关咨询的 84.4%）。在所有不当处方中，最常开出的抗生素是柬埔寨和马达加斯加的阿莫西林（分别为 42.1% 和 29.2%）和塞内加尔的头孢克肟 (31.2%)。与不适当处方风险增加相关的协变量包括患者年龄大于 3 个月（调整后的比值比 (aOR) 和 95% 置信区间 (95% CI) 在各国范围从 1.91 [1.63, 2.25] 到 5.25 [3.85, 7.15] , p < 0.001) 和生活在农村而不是城市环境 (aOR 在不同国家范围从 1.83 [1.57, 2.14] 到 4.40 [2.34, 8.28], p < 0.001)。具有较高严重程度评分的诊断也与不适当处方的风险增加相关（aOR = 2.00 [1.75, 2.30] 为中度严重，3.10 [2.47, 3.91] 为最严重，p < 0.001），就像在雨天咨询一样季节 (aOR = 1.32 [1.19, 1.47], p < 0.001)。我们研究的主要局限性是缺乏细菌学文件，这可能导致一些诊断错误分类和可能高估不适当的抗生素处方。结论 在这项研究中，我们在马达加斯加、塞内加尔和柬埔寨的儿科门诊患者中观察到大量不适当的抗生素处方。尽管在处方实践方面存在很大的跨国异质性，但我们确定了不适当处方的常见风险因素。