Proton pump inhibitors- increased mortality in patients with Clostridioides difficile infection by inducing gut dysbiosis

Background:Clostridioides difficile infection (CDI), a most important cause of antibiotics-associated diarrheachronic critical ill patientsdisease, is associated with high mortality.Antibiotics detrimentally change the gut microbiota (dysbiosis) with the consequence of CDI. However, the association of gut dysbiosis and CDI mortality remains unclear.Aims:This study aims to identify the factors of the mortality and its association with gut dysbiosis in chronic critical ill patients with CDI.Methods:Chronic critical ill patients with diarrhea were included and the diagnosis of CDI was determined by positive for a stool tcdB assay. The risk factors associated with mortality within 180 days were identified by cox regression analyses. Fecal microbiota were determined by sequencing of bacterial 16S rRNA.Results:During 2016/08-2018/07, there were 240 adult patients diagnosed as CDI, including 117 (48.8%) male and 123 female patients, respectively. Their mean age was 69.1 years. Thirty-six (15.0%) and 91 cases were dead within 30 and 180 days, respectively. Multivariate analysis revealed that, along with other risk factors, proton pump inhibitor (PPI) use was associated with overall mortality (p=0.032, estimated beta 1.024). Microbiota analyses showed the decreased relative abundance of Lachnospiracea and Clostridium cluster XIVa was associated with high mortality in CDI patients and had an inverse dose relationship with PPI. Similar PPI effects were also observed in over diarrhea patients.Conclusions:PPI use is an independent risk factor for the mortality of CDI patients by inducing gut dysbiosis, in particular, decreased the abundance of Lachnospiracea and Clostridium cluster XIVa. Our findings provide a notion of PPI use in patients with CDI.