BACKGROUND Vaccines for diarrhoea could have the ancillary benefit of preventing antibiotic use. We aimed to quantify and compare the expected impact of enteric vaccines on antibiotic use via Monte Carlo simulations. METHODS We analysed data from a longitudinal birth cohort, which enrolled children from 2009 to 2012 from Bangladesh, India, Nepal, Pakistan, and Tanzania. We used Monte Carlo simulations to estimate hypothetical vaccine impact in nine vaccination scenarios (including six single vaccines and three combination vaccines) on antibiotic- treated diarrhoea, overall antibiotic courses, and antibiotic exposures to bystander pathogens. For each vaccine scenario, we randomly selected target pathogen-specific diarrhoea episodes to be prevented according to the specified vaccine efficacy and estimated the absolute and relative differences in incidence of antibiotic use outcomes between vaccine and no vaccine scenarios. FINDINGS Among 1119 children, there were 3029 (135·3 courses per 100 child-years) antibiotic-treated diarrhoea episodes. Based on simulated results, a Shigella vaccine would cause the greatest reductions compared with the other single pathogen vaccines in antibiotic courses for all-cause diarrhoea (6·1% relative reduction; -8·2 courses per 100 child-years [95% CI -9·4 to -7·2]), antibiotic courses overall (1·0% relative reduction; -8·2 courses per 100 child-years [-9·4 to -7·2]), and antibiotic exposures to bystander pathogens (1·2% relative reduction; -15·9 courses per 100 child-years [-18·5 to -13·8]). An adenovirus-norovirus-rotavirus vaccine would cause the greatest reductions in antibiotic use (12·2 courses per 100 child-years [-13·7 to -11·0]) compared with the other combination vaccines. However, projected vaccine effects on antibiotic use in 2021 were 45-74% smaller than those estimated in 2009-12 accounting for reductions in diarrhoea incidence in the past decade. INTERPRETATION Vaccines for enteric pathogens could result in up to 8-12 prevented courses of antibiotics per 100 vaccinated children per year. Combination vaccines will probably be necessary to achieve greater than 1% reductions in total antibiotic use among children in similar low-resource settings. FUNDING Wellcome Trust and Bill & Melinda Gates Foundation.

中文翻译：

---

腹泻疫苗对 5 个资源匮乏地区儿童抗生素使用的影响：一项比较模拟研究。


背景 腹泻疫苗可能具有防止抗生素使用的辅助益处。我们旨在通过蒙特卡洛模拟量化和比较肠道疫苗对抗生素使用的预期影响。方法 我们分析了来自纵向出生队列的数据，该队列招募了 2009 年至 2012 年来自孟加拉国、印度、尼泊尔、巴基斯坦和坦桑尼亚的儿童。我们使用蒙特卡洛模拟来估计假设疫苗在 9 种疫苗接种情景（包括 6 种单一疫苗和 3 种联合疫苗）中对抗生素治疗腹泻、总体抗生素疗程和抗生素暴露于旁观者病原体的影响。对于每种疫苗情景，我们根据指定的疫苗功效随机选择要预防的目标病原体特异性腹泻事件，并估计接种疫苗和不接种疫苗情景之间抗生素使用结果发生率的绝对和相对差异。结果 在 1119 名儿童中，有 3029 例 （135·3 个疗程/100 儿童年） 抗生素治疗的腹泻发作。根据模拟结果，志贺菌疫苗在全因腹泻的抗生素疗程（相对减少 6·1%;每 100 儿童年 -8·2 个疗程 [95% CI -9·4 至 -7·2]）、总体抗生素疗程（相对减少 1·0%;每 100 个儿童年 -8·2 个疗程 [-9·4 至 -7·2]）、 以及旁观者病原体的抗生素暴露（相对减少 1·2%;每 100 儿童年 -15·9 个疗程 [-18·5 至 -13·8]）。与其他联合疫苗相比，腺病毒-诺如病毒-轮状病毒疫苗将导致抗生素使用量的最大减少（每 100 儿童年 12·2 个疗程 [-13·7 至 -11·0]）。 然而，预计 2021 年疫苗对抗生素使用的影响比 2009-12 年的估计值小 45-74%，这说明过去十年腹泻发病率的降低。解释 肠道病原体疫苗每年每 8 名接种疫苗的儿童可导致多达 12-100 个抗生素预防疗程。在类似的资源匮乏环境中，为了使儿童的抗生素总使用量减少 1% 以上，可能需要联合疫苗。资助 Wellcome Trust 和 Bill & Melinda Gates Foundation。