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高使用率、高耐药环境下,经验性抗菌治疗对儿科腹泻无临床获益。

No Clinical Benefit of Empirical Antimicrobial Therapy for Pediatric Diarrhea in a High-Usage, High-Resistance Setting.

机构信息

The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit.

Children's Hospital 1, Ho Chi Minh City, Vietnam.

出版信息

Clin Infect Dis. 2018 Feb 1;66(4):504-511. doi: 10.1093/cid/cix844.

Abstract

BACKGROUND

Pediatric diarrheal disease presents a major public health burden in low- to middle-income countries. The clinical benefits of empirical antimicrobial treatment for diarrhea are unclear in settings that lack reliable diagnostics and have high antimicrobial resistance (AMR).

METHODS

We conducted a prospective multicenter cross-sectional study of pediatric patients hospitalized with diarrhea containing blood and/or mucus in Ho Chi Minh City, Vietnam. Clinical parameters, including disease outcome and treatment, were measured. Shigella, nontyphoidal Salmonella (NTS), and Campylobacter were isolated from fecal samples, and their antimicrobial susceptibility profiles were determined. Statistical analyses, comprising log-rank tests and accelerated failure time models, were performed to assess the effect of antimicrobials on disease outcome.

RESULTS

Among 3166 recruited participants (median age 10 months; interquartile range, 6.5-16.7 months), one-third (1096 of 3166) had bloody diarrhea, and 25% (793 of 3166) were culture positive for Shigella, NTS, or Campylobacter. More than 85% of patients (2697 of 3166) were treated with antimicrobials; fluoroquinolones were the most commonly administered antimicrobials. AMR was highly prevalent among the isolated bacteria, including resistance against fluoroquinolones and third-generation cephalosporins. Antimicrobial treatment and multidrug resistance status of the infecting pathogens were found to have no significant effect on outcome. Antimicrobial treatment was significantly associated with an increase in the duration of hospitalization with particular groups of diarrheal diseases.

CONCLUSIONS

In a setting with high antimicrobial usage and high AMR, our results imply a lack of clinical benefit for treating diarrhea with antimicrobials; adequately powered randomized controlled trials are required to assess the role of antimicrobials for diarrhea.

摘要

背景

在中低收入国家,小儿腹泻病对公共卫生构成重大负担。在缺乏可靠诊断和高抗生素耐药性(AMR)的情况下,经验性抗生素治疗腹泻的临床益处尚不清楚。

方法

我们在越南胡志明市进行了一项前瞻性多中心横断面研究,纳入因腹泻伴血便和/或黏液而住院的儿科患者。测量临床参数,包括疾病结局和治疗。从粪便样本中分离志贺菌、非伤寒沙门氏菌(NTS)和弯曲菌,并确定其抗生素敏感性谱。采用对数秩检验和加速失效时间模型进行统计分析,以评估抗生素对疾病结局的影响。

结果

在 3166 名入选患者中(中位数年龄 10 个月;四分位距 6.5-16.7 个月),三分之一(3166 例中有 1096 例)有血便,25%(3166 例中有 793 例)培养出志贺菌、NTS 或弯曲菌。超过 85%的患者(3166 例中有 2697 例)接受了抗生素治疗;氟喹诺酮类是最常用的抗生素。分离出的细菌中存在高度的抗生素耐药性,包括对氟喹诺酮类和第三代头孢菌素的耐药性。抗生素治疗和感染病原体的多药耐药状态与结局无显著相关性。抗生素治疗与特定类型腹泻疾病的住院时间延长显著相关。

结论

在抗生素使用量大且 AMR 较高的环境中,我们的结果表明抗生素治疗腹泻没有临床获益;需要进行充分的、有对照的随机临床试验来评估抗生素在腹泻治疗中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d56/5850041/40647a49984e/cix84401.jpg

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