Clostridium Difficile Colonization And Infection In Patients With Hepatic Cirrhosis

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Clostridium difficile colonization and infection in patients with hepatic cirrhosisClostridium difficile infection(CDI)has been considered as a crucial factor affecting the public health.To date,up to 20-30%of the antibiotic-associated diarrhea(AAD)and nearly all the Pseudomembranous colitis(PMC)were associated with CDI.Patients with CD colonization have been considered as an important infectious source for CDI.Patients with hepatic cirrhosis are more susceptible to the alternation of gut bacteria due to portal hypertension,intestinal congestion,interruption of intestinal barrier function,as well as application of antacids and antibiotics,which results in decrease of probiotics,over-growth of conditioned pathogen and finally intestinal infection.For the patients with hepatic cirrhosis,many showed severe complications such as abdominal infection and alimentary tract hemorrhage,which then involved frequent utilization of antacids and anti-infective agents.This may induce alternations in gut bacteria and CDI,and even PMC.The symptom-free CD colonization patients and CDI patients may serve as important infectious source for CDI,which can contribute to the prevention of nosocomial infection.The purpose of this study is to investigate the CD colonization and infection in patients with hepatic cirrhosis,and analyze the risk factors of CD colonization as well as its correlation with CDI.In this study,526 hepatic cirrhosis patients were included in this study.Stool samples were collected to determine the CD and toxin,together with multilocus sequence typing(MLST).The patients were divided into C.difficile colonized(CDC)group and noncolonized(NC)group according to the colonization of toxin-expressing C.difficile.Comparison was performed to the gender,ratio of patients aged>65 yrs,causes of hepatic cirrhosis,multiple hospitalization,PTA decrease,complications and application of antibiotics.Multivariate Logistic regression analysis was carried out identify the risk factors for CD colonization.Meanwhile,the CDI during the hospitalization was analyzed.The results showed that 104 cases(19.8%)showed CD colonization among the 526 cases,with the ST-3,ST54,ST35 and ST37 serving as the predominant strains.Multvariate Logistic regression analysis indicated that CHILD grade C grade,(OR 3.025;95%CI 1.410-6.488),elevate of INR(OR 2.180;95%CI 1.368-3.476),decrease of PLT(OR 2.746;95%CI 0.931-8.103)and concurrent hepatic encephalopathy(OR 1.740;95%CI 1.012-2.990)were the risk factors for CD colonization in hepatic cirrhosis patients.During the hospitalization,the prevalence of CDI in the CDC group was higher than that of the NC group(26.0%vs.1.7%,P<0.001).Conclusion:The prevalence of CD colonization in toxin-expressing hepatic cirrhosis patients was 19.8%.The risk factors for CD colonization included CHILD grade(C grade),elevate of INR,decrease of PLT and concurrent hepatic encephalopathy.Besides,patients with CD colonization were more apt to develop CDI.Part ? Risk factors for CDI in hepatic cirrhosis patientsC.difficile is the major cause for the infectious diarrhea.CDI is reported to be associated with the host immunity,bacterial virulence and other factors such as senior age,antibiotics,proton pump inhibitors,antacids,nasal feeding,gastrointestinal.tract surgery and basic disorders.Patients with hepatic cirrhosis or liver transplantation recipients were usually hospitalized several times due to abdominal infection,upper gastrointestinal hemorrhage,and hepatic encephalopathy,which were featured by long hospitalization,as well as application of antibiotics and antacids that may:induce GDI.In this section,we aim to identify the risk factors in hepatic cirrhosis patients with CDI.A total of 526 cases admitted to our hospital between May 2015 and October 2015 were included in this study.The stool samples were collected upon admission to detect C.difficile and toxin.CDI was monitored during the hospitalization.In total,34 cases with hepatic cirrhosis showed CDI.Then we analyzed the effects of age,gender,CD colonization,multiple hospitalization,extended hospitalized delay,elevation of total bilirubin,creatinine(Cr)and INR,CHILD C grade,hepatic encephalopathy,hepatorenal syndrome,upper gastrointestinal hemorrhage,antibiotics and PPI exposure on the CDI in patients with hepatic cirrhosis.The results showed that the ratio of patients with multiple hospitalization,CD colonization,CHILD C grade,hepatic encephalopathy,hepatorenal syndrome,upper gastrointestinal hemorrhage,antibiotics and PPI exposure in the CDI group was significantly higher than that of the non-CDI group.Multiple Logistic regression analysis indicated that the risk factors of hepatic cirrhosis combined with CDI included aged>60 yrs(OR 1.689;95%CI 1.135-3.128),multiple hospitalization(OR 3.346;95%CI 1.392-8.043),hypoproteinemia(OR 4.962;95%CI 2.053-11.996),CD colonization(OR 18.410;95%CI 6.898-49.136),a hospitalization of>20 days(OR 1.564;95%CI 0.989-2.563),antibiotics(OR 1.865;95%CI 0.889-2.863),and PPI exposure(OR 3.125;95%CI 1.818-7.548).On this basis,it is necessary to pay attention to these factors,in order to improve the early diagnosis of CDI in hepatic cirrhosis patients and decrease the mortality.Part ? Roles of gut bacteria structural diversity in the pathogenesis of CDI in hepatic cirrhosis carrying Clostridium difficileCDI is one of the most common causes for infectious diarrhea.The prevalence of CDI in the hepatic cirrhosis patients is higher than the other populations due to presence of abdominal infection,upper gastrointestinal hemorrhage,hepatic encephalopathy,frequent hospitalization,longer hospitalization duration,as well as application of antibiotics and antiacid.In our previous study,we included 526 cases with hepatic cirrhosis.The CDI prevalence in the hepatic cirrhosis patients was 6.46%(34/526),which was superior to that of the patients without hepatic cirrhosis(5%).The CD colonization prevalence in the hepatic cirrhosis patients was 19.8%,which was higher than that of the other patients.What is the reason for the high prevalence of CD colonization and infection in patients with hepatic cirrhosis?In healthy individuals,the gut bacteria contributed to the resistance of pathogenic bacterial invasion.For the patients with CD colonization,some developed CDI,while the others were all in a state of colonization.Besides,the interference after admission,are there any differences in the gut bacteria before treatment?Are there any specific markers to predict the possibility of CDI?The gut bacteria could antagonize the C.difficile,which then protect the host from infection or being in a state of colonization.In cases of risk factors,such as anti-infective agents and antiacid,the enterobacteriaceae may present overgrowth and lead to damage of gut bacteria,which then results in intestinal microecology damage and subsequent accumulation of endotoxin,damage of intestinal mucous membrane,as well as endotoxemia and decreased colonization of gut bacteria.All these may induce CDI finally.In this study,hepatic cirrhosis patients carrying C.difficile were followed up.Then the stool samples were collected upon admission,followed by bacterial culture and toxin identification,as well as frozen storage.Patients with positive findings in the culture and toxin identification were included in this study,and were divided into CDI group and NCD group.Mesiq high throughput platform was used for the analysis of 16S rRNA V3 region.We then compared the structure diversity of gut bacteria in both groups,in order to identify the predicting indices for CDI carrying C.difficile.Our data showed that the sobs and ace showed significant decrease in the CDI group compared with those in the HC group.For the bacterial structure analysis,the Enterococcus and Escherichia showed significant increase in the CDI group compared with those of the NCD group and HC group.In contrast,the Bacteroides,Lactobacillus and Bifidobacterium showed significant decrease in the CDI group compared with those of the NCD group and HC group.The Bacteroidetes and Actinobacteria in the CDI group showed significant decrease compared with those of the NCD group and HC group,respectively.The Proteobacteria in the CDI group were significantly higher than those of the NCD group and HC group.PCoA analysis indicated the specification among these groups was satisfactory.The clarification for PCI,PC2 and PC3 was 25.04%,9.35%and 8.66%,respectively.The dispersion in the CDI and NCD groups was obvious than that of the HC group,indicating that there might be large differences in the gut bacterial structure in the CDI and NCD groups than that of the HC group.LEfSe analysis showed the number of Moraxella Fulton,Parabacteroides,Acinetobacter,Porphyromonadaceae and Terrisporobacter in the CDI group was significantly higher than that of the HC group and NCD group.The number of Clostridium,Clostridium,Bacteroidaceae,Bacteroides,Verrucomicrobiaceae,Clostridium leptum,Hungatella,Intestinebacter and Clostridium innocuum in the NCD group was significantly higher than that of the HC group and CDI group.For the HC group with no infection or not carrying the C.difficile,the number of C.innocuum,Prevotellaceae,Micrococcus,Eubacterium hallii,Coriobacteriaceae,Coriobacteride,Dorea,and Lachnospira was significantly higher than that of the NCD group and CDI group.Therefore,gut bacterial diversity could be used to predict the onset of CDI.CD carrying patients with elevation of Moraxella Fulton,Parabacteroides,Acinetobacter,and Porphyromonadaceae and decrease of Bacteroides and Lachnospira as well diversity are more susceptible to CDI,which may predict the possibility of CDI in the hepatic cirrhosis patients.The Bacteroides and Lachnospira are more apt to present in the normal individuals,which may exert protective roles in preventing CDI and may be a candidate agent for prevention of CDI.