Clinical Characteristics And Risk Factor Analysis Of Clostridium Difficile Infection In Inflammatory Bowel Disease Patients

BackgroundClostridium difficile?C.difficile?is a Gram-positive,spore-forming anaerobe.Clostridium difficile infection?CDI?can cause a spectrum of disease ranging from asymptomatic carriers or mild diarrhea to fulminant infectious colitis occasionally complicated by toxic megacolon,sepsis,and death.Inflammatory bowel disease?IBD?,comprised of Crohn's disease?CD?and ulcerative colitis?UC?,are chronic,idiopathic inflammatory gastrointestinal disorders.The main clinical manifestations are diarrhea in both IBD flares and CDI,such overlap in symptomatology complicates the diagnosis of CDI in IBD patients.In addition,they are significantly different in treatment.Therefore,it is necessary to identify CDI that may be complicated in patients with IBD.Generally,CDI is associated with the use of antibiotic and hospitalization.However,IBD patients,as a special susceptible population,still remain unknown whether their prevalence and risk factors of CDI are the same with the general population.Till now,only a few related researches were reported in IBD patients.In order to provided a basis for the transmission of C.difficile in shanghai,a research about the clinical and molecular characteristics of C.difficile in IBD population has been conducted.MethodsFrom July 1^st 2014 to June 30^th 2017,stool samples of the inpatients at Renji Hospital affiated to Shanghai Jiaotong University were collected.All the samples were inoculated onto CDIF medium under anaerobic environment and use toxin A and B enzyme immunoassays to detect toxins.Cultural-positive strains were then identified by biochemical reactions and MALDI-TOF MS.Collect the clinical data of the cultural-positive strains as well as their multilocus sequence typing.And compare the information of IBD population to those of non-IBD patients to observe special characteristics in IBD population.In addition,IBD patients with CDI were matched with1:1 non-CDI controls randomly selected for each case of CDI in the same inpatient care unit and the same period of time within five days of admission.Demographic clinical variables were analyzed between the two groups so as to find potential risk factors for CDI among IBD population.Results1?In this study,a total of 3600 specimens of fecal specimens were collected,of which 365 samples were tested Clostridium difficile infection positive.After removing duplicate samples and samples with incomplete clinical information,a total of 330strains were obtained.143 strains were isolated from IBD patients,with an infection rate of 12.4%;while 187 colonies were isolated from non-IBD patients,with the rate of 7.6%.The infection rate of C.difficile in patients with IBD was significantly higher than that in non-IBD patients??2=21.837,p<0.001?.When further investigating the disease classification of patients with IBD,we found that the infection rate of C.difficile in Crohn's disease patients?16.0%?was significantly higher than that in patients withulcerative colitis?7.1%???2=21.007,p<0.001?.The positive rate of C.difficile in culture among IBD patients was higher than that in toxin test?8.8%vs.4.9%,?2=11.192,P=0.001?.The combined detection of the two methods could improve the positive rate of C.difficile.2?The positive rate of C.difficile culture test in IBD patients was higher than that of toxin test?8.8%vs.4.9%,2=11.192,P<0.001?.When compared with the gold standard og culture,the sensitivity and positive predictive value of toxin detection were26.9%and 35.8%respectively.And the specificity and negative predictive value were88.9%and 84.1%respectively.The false negative rate of toxin detection was 73.1%,which made it difficult to identify C.difficile infection in IBD patients.The detection rate of CDI can be improved by the combined detection of the two methods.3?Comparing the clinical data of C.difficile infection patients with IBD and without IBD,we found that the age of IBD patients was significantly younger than that of non-IBD patients?37±14 vs.65±20,p<0.001?,and the average hospitalization time of IBD patients was shorter than that of non-IBD patients?17±11vs.35±26,p<0.001?.The type of C.difficile infection in IBD patients were more likely to be community-acquired?Median=2 days?,while in non-IBD patients were more likely to acquire hospital infection?Median=7 days?.When analyzing the systemic infection indicators of the two groups,we found that C-reactive protein?14.87±23.05 vs.36.00±47.99,p<0.001?,procalcitonin?0.07±0.13 vs.1.27±5.81,p<0.001?,hematocyte sedimentation rate?20.98±19.10 vs.35.33±29.02,p<0.001?,neutrophil ratio?65.75±11.70%vs.69.11±14.57%,p=0.004?in IBD patients were lower than those in non-IBD patients,which indicating that the systemic infection symptoms in IBD patients were milder.However,the indexes of intestinal infection in IBD groups,including fecal white blood cells?6.94±20.95 vs.1.50±8.80,p=0.005?,fecal red blood cells?4.35±16.82 vs.0.19±1.07,p=0.003?,occult blood?+vs.-,p=0.014?were higher than those in non-IBD patients,indicating that symptoms of intestinal infection in IBDpatients were more severe.The level of serum albumin was slightly higher than that of non-IBD patients?39.35±6.39 vs.34.13±6.87,p<0.001?,and creatinine was lower than that of non-IBD patients?66.44±16.60 vs.108.15±131.80,p=0.046?.As the albumin and creatinine of both groups were within the normal range,there were statistical differences but no clinical significance.Molecular epidemiological data showed that ST54 was the most common ST type in IBD patients with C.difficile infection,followed by ST2 and ST3,as ST81 in non-IBD patients with C.difficile infection,followed by ST2 and ST54.The ST types of C.difficile infected by IBD patients with different severities were not entirely the same.Overall,the most common types in mild to moderate IBD patients were ST54,ST2,ST48,as in severe IBD patients were ST54,ST3 and ST39.Further subdividing IBD diseases,we found that C.difficile ST54 was most common in moderate to severe UC patients and mild to moderate CD patients,and C.difficile ST39 and ST3 were most found in severe CD patients.4?143 IBD patients with C.difficile infection were matched 1:1 IBD patients without C.difficile infection.Comparison of the clinical data in both groups have shown C.difficile infection was mostly concentrated in moderate to severe IBD patients??2=13.364,p=0.001?.Risk factors analysis showed that the previous intestinal surgery was the risk factor for CDI in IBD patients?OR=3.53,95%CI=1.46-8.56,P=0.003?;cephalosporins?OR=1.06,95%CI=0.66-1.69,P=0.812?,and quinolone antibiotics?OR=1.29,95%CI=0.81-2.05,P=0.287?were not related to the occurrence of CDI in IBD patients.Use antibiotics alone or federally were not associated with the occurrence of CDI in IBD patients.Antibiotics were also not associated with the occurrence of CDI in IBD patients?OR=0.78,95%CI=0.38-1.56,p=0.476?.The types and dosages of IBD drugs,including glucocorticoids?OR=0.87,95%CI=0.31-2.48,p=0.795?,infliximab?OR=1.04,95%CI=0.37-2.98,p=0.938?,immunosuppressants?OR=0.59,95%CI=0.25-1.43,p=0.240?were not associated with the occurrence of CDI in IBD patients.Conclusion1?The positive rate of C.difficile culture in IBD patients?8.8%?was higher than that of toxin detection?4.9%?.The total infection rate of C.difficile in IBD patients was12.4%,significantly higher than that in non-IBD patients?7.6%?hospitalized in the same period,and the incidence of C.difficile infection in CD patients was higher than that in UC patients?16.0%vs.7.1%?.2?The false negative rate of toxin detection was as high as 73.1%.The positive rate of C.difficile infection in IBD patients can be improved by the combined detection of the two methods.3?Compared with non-IBD patients with C.difficile infection,IBD patients with C.difficile infection were younger and had shorter hospitalization time.Most of the infections in IBD patient were community-acquired,while in non-IBD patients were hospital-acquired.IBD patients have better nutritional status,less systemic inflammatory reaction and more severe intestinal infections.Molecular epidemiological data showed that the most common type of C.difficile infected in IBD patients was ST54,while in non-IBD patients was ST81.ST54 was most common in patients with moderate to severe ulcerative colitis and patients with mild to moderate Crohn's disease.ST39/ST3was most common in patients with severe Crohn's disease.4?This study only found that the history of intestinal surgery was a risk factor for C.difficile infection in IBD patients.Antibiotics,immunosuppressants,glucocorticoids and infliximab were not associated with C.difficile infection in IBD patients.