Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature

BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

Therapeutics involved in managing initial and recurrent Clostridium difficile infection:An updated literature review

Clostridium difficile infection(CDI)has been increasing due to the effect of recurrent hospitalizations.The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs.The treatment is limited to three major antibiotics;however,the incidence of recurrent CDIs has been increasing and drug resistance is a major concern.This aspect is a growing concern in modern medicine especially in the elderly population,critical care patients,and immunocompromised individuals who are at high risk of developing CDIs.Clostridium difficile can lead to various complications including septic shock and fulminant colitis that could prove to be lethal in these patients.Newer modalities of treatment have been developed including bezlotoxumab,a monoclonal antibody and fecal microbiota transplant.There have been studies showing asymptomatic carriers and drug resistance posing a major threat to the healthcare system.Newer treatment options are being studied to treat and prevent CDIs.This review will provide an insight into the current treatment modalities,prevention and newer modalities of treatment and challenges faced in the treatment of CDIs.

Recurrent Clostridium difficile infections:The importance of the intestinal microbiota

Clostridium difficile infections(CDI)are a leading cause of antibiotic-associated and nosocomial diarrhea.Despite effective antibiotic treatments,recurrent infections are common.With the recent emergence of hypervirulent isolates of C.difficile,CDI is a growing epidemic with higher rates of recurrence,increasing severity and mortality.Fecal microbiota transplantation(FMT)is an alternative treatment for recurrent CDI.A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach.FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI.Since the first reported use of FMT for recurrent CDI in 1958,systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment.This article focuses on current guidelines for CDI treatment,the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy,adverse effects and acceptability.

Management of inflammatory bowel disease with Clostridium difficile infection

To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. METHODSA systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations. RESULTSIn those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not. CONCLUSIONStrong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.

Antibiotic prophylaxis in variceal hemorrhage:Timing,effectiveness and Clostridium difficile rates

AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken.The primary outcome measure was 28-d mortality.Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI.All patients were admitted to a tertiary liver unit with a consultantled,24-h endoscopy service.Patients received standard care including terlipressin therapy.Data collection included:primary and secondary outcome measures,timing of first administration of intravenous antibiotics,eti-ology of liver disease,demographics,endoscopy details and complications.A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration.Statistical analysis was undertaken using univariate,non-parametric tests and multivariate logistic regression analysis.RESULTS:There were 70 first presentations of variceal hemorrhage during the study period.Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease.In total,64/70(91.4%) patients received antibiotics as prophylaxis during their admission.Specifically,53/70(75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy(8 h) group],whereas 17/70(24.3%) received antibiotics at > 8 h after endoscopy or not at all(non peri-endoscopy group).Overall mortality and rebleeding rates were 13/70(18.6%) and 14/70(20%),respectively.The periendoscopy(8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%,P = 0.04,odds ratio(OR) = 0.28(0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%,P = 0.27,OR = 0.49(0.14-1.74)].On univariate analysis,the non peri-endoscopy group [P = 0.02,OR = 3.58(1.00-12.81)],higher model for end-stage liver disease(MELD) score(P = 0.02),presence of hepatorenal syndrome [P < 0.01,OR = 11.25(2.24-56.42)] and suffering a clinical episode of sepsis [P = 0.03,OR = 4.03(1.11-14.58)] were significant predictors of death at 28 d.On multivariate logistic regression analysis,lower MELD score [P = 0.01,OR = 1.16(1.04-1.28)] and periendoscopy(8 h) group [P = 0.01,OR = 0.15(0.03-0.68)] were independent predictors of survival at 28 d.The CDI incidence(5.7%) was comparable to that in the general medical population(5%).CONCLUSION:Antibiotics administered up to 8 h following endoscopy were associated with improved survival at 28 d.CDI incidence was comparable to that in other patient groups.

Clostridium difficile infections in China

Clostridium difficile （C.difficile） infection has become one of the major hospital-associated infections in Western countries in the last two decades.However,there is limited information on the status of C.difficile infection in Chinese healthcare settings.Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China,it is critical to understand the epidemiology and potential risk factors that may contribute to C.difficile infection in China.A literature review of available published studies,including those in Chinese language-based journals,was conducted.A review of the currently available literature suggested the presence of C.difficile infections in China,but also suggested that these infections were not particularly endemic.This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C.difficile infection in China,including the identification of any associated risk factors.Such information is ultimately valuable to develop appropriate strategies to prevent C.difficile infection and the vast negative impact of such infections in China and other developing countries.

Impact of Clostridium difficile infection on inflammatory bowel disease outcome: A review

Although a considerable number of studies support a substantial increase in incidence, severity, and healthcare costs for Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD), only few evaluate its impact on IBD outcome. Medline and several other electronic databases from January 1993 to October 2013 were searched in order to identify potentially relevant literature. Most of the studies showed that IBD patients with CDI present a greater proportion of worse outcomes than those without CDI. These patients have longer length of hospital stay, higher rates of colectomies, and increased mortality. Patients with ulcerative colitis are more susceptible to CDI and have more severe outcomes than those with Crohn&#x02019;s disease. However, studies reported variable results in both short- and long-term outcomes. Contrasting results were also found between studies using nationwide data and those reporting from single-center, or between some North-American and European studies. An important limitation of all studies analyzed was their retrospective design. Due to contrasting data often provided by retrospective studies, further prospective multi-center studies are necessary to evaluate CDI impact on IBD outcome. Until then, a rapid diagnosis and adequate therapy of infection are of paramount importance to improve IBD patients&#x02019; outcome. The aim of this article is to provide up to date information regarding CDI impact on outcome in IBD patients.

Current knowledge on the laboratory diagnosis of Clostridium difficile infection

Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from selflimited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI.

Clostridium difficile causing acute renal failure: Case presentation and review

AIM: Clostridium difficile infection is primarily a nosocomial infection but asymptomatic carriers of Clostridium difficile can be found in up to 5% of the general population. Ampicillin, cephalosporins and clindamycin are the antibiotics that are most frequently associated with Clostridium difficile-associated diarrhea or colitis. Little is known about acute renal failure as a consequence of Clostridium difficile-associated diarrhea. METHODS: In this case report, we describe the course of Clostridium difficile-associated diarrhea in an 82-year-old patient developing acute renal failure. Stopping the offending agent and symptomatic therapy brought a rapid improvement of diarrhea and acute renal failure, full recovery was gained 18 d after admission. In a systematic review we looked for links between the two conditions. RESULTS: The link between Clostridium difficile-assoaated diarrhea and acute renal failure in our patient was most likely volume depletion. However, in experimental studies a direct influence of Clostridium difficile toxins on renal duct cells could be shown. CONCLUSION: Rapid diagnosis, nonspecific supportive treatment and specific antibiotic treatment, especially in the elderly, may lower excess mortality Clostridium difficile-associated diarrhea and renal failure being possible complications.

Global research on Clostridium difficile-associated diarrhoea:A visualized study

BACKGROUND Clostridioides(Clostridium)difficile(C.difficile)is still the most common cause of healthcare-associated diarrhoea and is increasing in prevalence as a communityacquired infection.In addition,the emergence of antibiotic resistance in C.difficile can increase the likelihood of the disease developing and/or spreading.AIM To provide an up-to-date picture of the trends in publications related to C.difficile infection,together with specific insights into hot-button issues in this field.METHODS Publications on C.difficile infections in the field of microbiology between 2001 and 2020 were identified from the Scopus database and Reference Citation Analysis.Bibliometric indicators were determined,including the number and type of publications,countries,affiliations,funding agencies,journals and citation patterns.VOSviewer was used to determine research areas and hot-button issues by identifying recurring terms with a high relative occurrence in the title and abstract.RESULTS A total of 8127 documents on‘C.difficile-associated diarrhoea’published between 2001 and 2020 were retrieved from the Scopus database.In the last decade,there has been a significant almost fourfold increase in the number of published papers on this topic.The United States was among the countries(44.11%)with the most publications,and the most involved institution was the University of Leeds in the United Kingdom(2.50%).Three clusters of research were identified and included‘illness spectrum and severity,as well as the signs,symptoms and clinical pathogenesis of C.difficile’;‘laboratory diagnosis and characterization of C.difficile’and‘risk factors for C.difficile infection’.CONCLUSION This study contains the most up-to-date and comprehensive data ever compiled in this field.More international research and cross-institutional collaborations are needed to address more global C.difficile concerns and to benefit from greater sharing of expertise,which will result in higher quality or more effective studies in the future.Promising research avenues in the near future may draw the attention of relevant scientists and funding organizations and open up novel C.difficile infection–based diagnosis and treatment approaches.

Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications:A case series

Fecal microbiota transplantation(FMT) is effective in recurrent Clostridium difficile infection(r CDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides r CDI. Among our FMT-treated r CDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than r CDI: Salmonella carriage(two patients), trimethylaminuria(two patients), small intestinal bacterial overgrowth(SIBO;one patient), and lymphocytic colitis(one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli(E. coli) carriage. Of the thirteen r CDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with r CDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia.Clostridium difficile infection(CDI)is a common nosocomial diarrheal disease.Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI.The use of broadspectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome.Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI.Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

Recent developments on the role of Clostridium difficile in inflammatory bowel disease

Clostridium difficile (CD), specifically its toxins, have been implicated as a risk factor for exacerbation of the inflammatory process in up to 5% of patients with ulcerative colitis or Crohn’s disease. Typical evidence of colonic changes with CD infection, including pseudomembranous exudate, are often not present; however, a severe clinical course may result, including precipitation of toxic colitis and toxic megacolon. Recently, hypervirulent CD strains have been reported raising concern for a more severe disease process in patients with underlying inflammatory bowel disease.Moreover, small bowel involvement or CD enteritis has been increasingly described, usually in those with a history of a prior colectomy or total proctocolectomy for prior severe and extensive inflammatory bowel disease. Finally, refractory or treatment-resistant pouchitis may occur with CD infection.

Univariate and multivariate analysis of risk factors for severe clostridium difficile-associated diarrhoea: Importance of co-morbidity and serum C-reactive protein

AIM: To investigate risk factors for severe clostridium difficile associated diarrhoea (CDAD) in hospitalised patients. METHODS: We analysed risk factors for severe CDAD (associated with systemic signs of hypovolemia) in 124 hospitalised patients by retrospective chart review. RESULTS: Severe CDAD was present in 27 patients (22%). Statistical analysis showed a significant association with a higher 30-d mortality (33% vs 4%, P < 0.001) and a higher proportion of longer hospital stay exceeding 14 d (74% vs 52%, P = 0.048). Charlson co-morbidity score (OR 1.29 for 1 point increment, P < 0.05) and serum C-reactive protein at diagnosis (OR 1.15 for 10 mg/L increment, P < 0.001) were independent predictors of severe CDAD. CONCLUSION: Patients with a severe level of co- morbidity and high serum C-reactive protein levels at the time of diagnosis should receive particular attention.

Ulcerative colitis worsened after Clostridium difficile infection:Efficacy of infliximab

The incidence of Clostridium difficile (C. difficile) infection (CDI) is 1.8%-5.7% in admitted patients with ulcerative colitis (UC). CDI can worsen UC and increase the risk for colectomy or even death, thus necessitating therapy escalation, such as increasing the corticoid therapy or starting a biologic treatment. Several reported cases with infliximab therapy have provided favorable outcomes in UC patients with CDI, suggesting that infliximab treatment may be protective; however, the optimal infliximab treatment regimen for UC patients with CDI remains to be established. Here, we report a case of worsening UC in the presence of recurrent CDI. The patient had received prior ciprofloxacin and immunosuppressive therapy during a prolonged hospital stay. The deterioration in the patient&#x02019;s condition likely resulted from the ability of C. difficile to promote relapsing of UC by activating the immune response. Ultimately, the patient was treated with a high dose of infliximab after a low trough level of infliximab at week 8 was identified, yielding better clinical results. Infliximab was found to be safe after repetitive episodes of CDI. The trough level of infliximab was therefore a useful indicator to guide therapy and correlated well with the patient&#x02019;s outcome.

Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice

AIM: To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10-/-) mouse model of inflammatory bowel disease.

Prophylactic antibiotics for variceal hemorrhage: Clostridium difficile infection still can be a risk

Bron et al presented a retrospective study regarding the prophylactic use of antibiotics for variceal hemorrhage. Antibiotics appeared to improve the survival rate of patients without increasing clostridium difficile infection (CDI). We argue against the conclusion of the authors and consider that this result may be simply due to concurrent use of metronidazole, a therapeutic agent against CDI.

Prevalence of diverticulosis in recurrent Clostridium difficile infection

AIM:To re-evaluate the theory that colonic diverticulosis is associated with relapse of Clostridium difficile associated disease (CDAD) in light of data suggesting increasing rates of CDAD infection and relapse.METHODS: Charts were reviewed for patients with recurrent CDAD who had also had a prior colonoscopy or flexible sigmoidoscopy. An age and gender matched control group was used to compare the prevalence of diverticulosis.RESULTS: Twenty-two patients met the study criteria, and the prevalence of diverticulosis in patients with CDAD relapse was 23% compared to 32% in age and sex matched controls (P=0.44). A significant proportion of patients with CDAD relapse had comorbidities associated with immune suppression.CONCLUSION: Diverticulosis does not appear to be associated with CDAD relapse.

Hematologic diseases: High risk of Clostridium difficile associated diarrhea

AIM: To investigate the incidence and clinical outcome of Clostridium difficile (C. difficile) associated diarrhea (CDAD) in patients with hematologic disease.

Did the severe acute respiratory syndrome-coronavirus 2 pandemic cause an endemic Clostridium difficile infection?

BACKGROUND Clostridium difficile infection(CDI)has increased in prevalence during the last years.The coronavirus disease 2019(COVID-19)pandemic has negatively influenced patient outcomes.The majority of the severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)-infected patients received antibiotics during hospitalization.AIM To analyze the factors that influenced CDI development after SARS-CoV-2 infection.METHODS Between March 2020 to December 2020,we performed a prospective observational study including 447 patients diagnosed with CDI who were admitted to our tertiary referral university hospital.The diagnosis of CDI was based on the presence of diarrhea(≥3 watery stools within 24 h)associated with Clostridium difficile toxins A or B.We excluded patients with other etiology of acute diarrhea.RESULTS Among the total 447(12.5%)patients with CDI,most were male(54.3%)and mean age was 59.7±10.8 years.Seventy-six(17.0%)had history of COVID-19,most being elderly(COVID-19:62.6±14.6 years vs non-COVID-19:56.8±17.6 years,P=0.007),with history of alcohol consumption(43.4%vs 29.4%,P=0.017),previous hospitalizations(81.6%vs 54.9%,P<0.001)and antibiotic treatments(60.5%vs 35.5%,P<0.001),requiring higher doses of vancomycin and prone to recurrent disease(25.0%vs 13.1%,P=0.011).Age over 60 years[odds ratio(OR):2.591,95%confidence interval(CI):1.452-4.624,P=0.001],urban residence(OR:2.330,95%CI:1.286-4.221,P=0.005),previous antibiotic treatments(OR:1.909,95%CI:1.083-3.365,P=0.025),previous hospitalizations(OR:2.509,95%CI:1.263-4.986,P=0.009)and alcohol consumption(OR:2.550,95%CI:1.459-4.459,P=0.001)were risk factors of CDI in COVID-19.CONCLUSION CDI risk is unrelated to history of SARS-CoV-2 infection.However,previous COVID-19 may necessitate higher doses of vancomycin for CDI.