Proton pump inhibitors and the risk of Clostridioides difficile infection: A systematic review and dose-response meta-analysis

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection Pub Date : 2025-04-14 DOI:10.1016/j.jinf.2025.106488

Matilda Finke , Annelies Boven , Erika Vlieghe , Lars Engstrand , Nicola Orsini , Nele Brusselaers

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引用次数: 0

Abstract

Background

Clostridioides difficile is a leading cause of healthcare-associated infections globally with proton pump inhibitor (PPI) use as important modifiable risk factor. This study aimed to systematically synthesise global evidence on the dose-response relationship of PPI usage and the Clostridioides difficile infection (CDI) risk and to identify potential safe thresholds of PPI usage regarding CDI.

Methods

PubMed, Embase, Web of Science, and Cochrane Library were searched for longitudinal studies regarding PPIs and CDI. Aggregated data were included in two separate two-stage random-effects dose-response meta-analyses regarding Defined Daily Dose (DDD) and PPI therapy duration. Pooled adjusted relative risks (RRs) with 95% confidence intervals compared to non-users of PPIs were estimated.

Findings

Overall, 15 observational cohort and case-control studies were included with 7 studies (n=483,821) in the meta-analysis per DDD and 7 studies (n=516,441) per PPI therapy duration. The risk of bias was modest. Pooled dose-response estimates suggest linear trends with a RR of 1^.05 (95% CI 0^.89,1^.23) per 10 mg DDD and of 1^.02 (95% CI 1^.00,1^.05) per day of PPI therapy. Substantial residual heterogeneity was detected in both analyses (I2=91^.4% per DDD and I2=99^.4% per therapy duration), but inferring potential sources was limited.

Interpretation

Our results indicate a possible increase in the risk of CDI with increasing dose and duration of PPI therapy. Underlying mechanisms and dosage thresholds for a clinically relevant risk increase remain unclear.

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质子泵抑制剂与艰难梭菌感染的风险：一项系统评价和剂量反应荟萃分析

背景艰难梭菌是全球医疗保健相关感染的主要原因，质子泵抑制剂（PPI）的使用是重要的可改变的危险因素。本研究旨在系统地综合关于PPI使用与艰难梭菌感染（CDI）风险的剂量-反应关系的全球证据，并确定关于CDI的PPI使用的潜在安全阈值。方法检索spubmed、Embase、Web of Science和Cochrane Library，检索PPIs和CDI的纵向研究。汇总数据纳入两个独立的两阶段随机效应剂量反应荟萃分析，涉及定义日剂量（DDD）和PPI治疗持续时间。与未使用ppi的患者相比，估计合并调整相对风险（rr）为95%置信区间。总的来说，15项观察性队列研究和病例对照研究被纳入meta分析，每个DDD有7项研究（n=483,821），每个PPI治疗持续时间有7项研究（n=516,441）。偏倚风险不大。合并剂量-反应估计显示线性趋势，每10 mg DDD的RR为1.05 (95% CI 0.89,1.23)，每天PPI治疗的RR为1.02 （95% CI 1.00,1.05）。两项分析均检测到大量残留异质性（每个DDD I2=91.4%，每个疗程I2=99.4%），但推断潜在来源有限。我们的研究结果表明，随着PPI治疗剂量和持续时间的增加，CDI的风险可能会增加。临床相关风险增加的潜在机制和剂量阈值仍不清楚。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.