Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Chang Gung University College of Medicine, Taoyuan, Taiwan.
Microbiol Spectr. 2022 Aug 31;10(4):e0048622. doi: 10.1128/spectrum.00486-22. Epub 2022 Jul 6.
Clostridioides difficile infection (CDI) is associated with high mortality rates among patients with chronic illnesses. We aimed to identify avoidable risk factors to reduce the mortality rate in CDI patients. A total of 306 patients with diarrhea and clinical suspicion of CDI were enrolled, and fecal samples were gathered from 145 patients. CDI was diagnosed by fecal positivity for the C. difficile gene. Risk factors associated with death within 180 days were identified using Cox regression analysis. The fecal microbiota was determined through bacterial 16S rRNA gene sequencing. Of the patients with diarrhea, 240 (mean age, 69.1 years) were positive for CDI, and 91 died within 180 days. Multivariate analysis revealed that male sex, high Charlson Comorbidity Index and McCabe scores, high serum C-reactive protein levels, low hematocrit levels, low absolute eosinophil counts, high neutrophil/lymphocyte ratios, and daily use of proton pump inhibitors (PPIs) were independent risk factors for overall mortality. Cumulative analyses confirmed the association of duration-dependent PPI use with a high mortality rate. Fecal microbiota analyses showed associations of decreased relative abundance of Ruminococcus gnavus ( = 0.001) and Prevotella copri ( = 0.025) and increased relative abundance of Parabacteroides merdae ( = 0.001) and Clostridioides difficile ( = 0.040) with higher mortality rates in patients with CDI. Moreover, these microbiota changes were correlated with the duration of PPI use. This article demonstrates that daily PPI use was the only avoidable risk factor for death. With more extended PPI use, the mortality rate was higher in patients with CDI. Decreases in Prevotella copri and Ruminococcus gnavus and increases in Parabacteroides merdae and Clostridioides difficile in line with daily PPI use duration were significantly associated with the death of CDI patients. Our findings provide in-depth insights into the cautious use of PPIs in chronically ill patients with CDI.
艰难梭菌感染（CDI）与慢性病患者的高死亡率相关。我们旨在确定可避免的危险因素，以降低 CDI 患者的死亡率。共纳入 306 例腹泻且临床怀疑 CDI 的患者，采集了 145 例患者的粪便样本。通过粪便中 C. difficile 基因阳性诊断 CDI。采用 Cox 回归分析确定 180 天内死亡的相关危险因素。通过细菌 16S rRNA 基因测序确定粪便微生物群。在腹泻患者中，240 例（平均年龄 69.1 岁）CDI 阳性，91 例在 180 天内死亡。多变量分析显示，男性、高 Charlson 合并症指数和 McCabe 评分、高血清 C 反应蛋白水平、低血细胞比容、低绝对嗜酸性粒细胞计数、高中性粒细胞/淋巴细胞比值和每日使用质子泵抑制剂（PPIs）是总死亡率的独立危险因素。累积分析证实了 PPI 使用时间依赖性与高死亡率相关。粪便微生物群分析显示，相对丰度降低的 Ruminococcus gnavus（ = 0.001）和 Prevotella copri（ = 0.025）以及相对丰度增加的 Parabacteroides merdae（ = 0.001）和 Clostridioides difficile（ = 0.040）与 CDI 患者死亡率升高相关。此外，这些微生物群变化与 PPI 使用时间相关。本文表明，每日 PPI 使用是导致死亡的唯一可避免危险因素。随着 PPI 使用时间的延长，CDI 患者的死亡率更高。与每日 PPI 使用时间一致的 Prevotella copri 和 Ruminococcus gnavus 减少以及 Parabacteroides merdae 和 Clostridioides difficile 增加与 CDI 患者的死亡显著相关。我们的研究结果深入了解了在患有 CDI 的慢性病患者中谨慎使用 PPI。
