Guideline sources The following summarized guidelines for the evaluation and management of clostridioides difficile infection (CDI) are prepared by our editorial team based on guidelines from the European Society for Microbiology and Infectious Diseases (ESCMID 2021; 2016), the World Society of Emergency Surgery (WSES/AAST 2021), the American College of Gastroenterology (ACG 2021; 2019; 2018; 2013), the American Society of Colon and Rectal Surgeons (ASCRS 2021), the Infectious Diseases Society of America (IDSA/SHEA 2021; 2018), the American Gastroenterological Association (AGA 2020; 2017), the World Society of Emergency Surgery (WSES 2019), the Healthcare Infection Society (HIS/BSG 2018), the Infectious Diseases Society of America (IDSA 2017; 2015), and the Eastern Association for the Surgery of Trauma (EAST 2014). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 20 21 Definition https://web.pathway.md/diseases/recQxWZGEt8jznT23 1/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway CDI is an antibiotic-induced infectious diarrheal disease that is associated with significant mortality and morbidity. 18 Epidemiology The shift in intestinal microbiota induced by repeated antibiotic use facilitates C. difficile colonization in the colon, with production of exotoxins (TcdA and TcdB) that cause colonocyte death. 20 Pathophysiology The incidence of CDI is estimated at 1.1-631.8 cases per 100,000 person-years. In patients admitted to the ICU, the incidence of CDI is estimated at 11.1 cases per 1,000 admissions-year (95% CI, 7.2-17.1), while in patients admitted to the internal medicine ward, it is estimated at 10.8 cases per 1000 admissions-year (95% CI, 3.2-37.1). 19 Disease course The resultant loss of intestinal barrier function leads to clinical manifestations of diarrhea, and can progress to pseudomembranous colitis, toxic megacolon, bowel perforation, sepsis, shock, multiple organ failure, and death. 21 Prognosis and risk of recurrence CDI has a mortality of 5% and is associated with a recurrence rate of 20-60%. 20 Guidelines 1. Screening and diagnosis Epidemiology: use standardized case definitions for surveillance of healthcare facility-onset C. difficile infection, community-onset, healthcare facility-associated C. difficile infection, and community-associated C. difficile infection, to increase comparability between clinical settings. B Show 6 more Indications for screening (asymptomatic individuals): insufficient evidence to recommend screening for asymptomatic carriage of C. difficile and placing asymptomatic carriers on contact precautions. I Indications for screening (patients on tube feeding): obtain clinical monitoring in patients with tube feeding due to their risk for developing C. difficile infection. B Indications for testing, adult patients: As per ACG 2021 guidelines, obtain testing for C. difficile infection only in patients with symptoms suggestive of active ( 3 unformed stools in 24 hours). B As per WSES 2019 guidelines, obtain testing for C. difficile infection in at-risk patients with clinically significant diarrhea ( 3 loose stools in 24 hours) with no obvious alternative explanation. B https://web.pathway.md/diseases/recQxWZGEt8jznT23 2/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway As per SHEA/IDSA 2018 guidelines, consider testing for C. difficile infection in patients with unexplained new-onset 3 unformed stools in 24 hours. C As per IDSA 2017 guidelines, consider testing for C. difficile infection in patients with persistent diarrhea without an etiology and recognized risk factors. C Show 3 more As per IDSA 2015 guidelines, avoid testing for C. difficile infection in the absence of diarrhea unless ileus due to C. difficile is suspected. D Indications for testing, pediatric patients: As per SHEA/IDSA 2018 guidelines, do not test for C. difficile infection routinely in neonates or infants 12 months of age with diarrhea because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants. D Show 2 more As per IDSA 2017 guidelines, consider testing for C. difficile infection in > 2 years old patients with a history of diarrhea following antimicrobial use. B 2. Classification and risk stratification Risk assessment: Recognize that older age (> 65 years old) and multiple comorbidities are risk factors for C. difficile infection. B Recognize the following risk factors for recurrent C. difficile infection: prior C. difficile infection episode B prior hospitalization in the last 3 months B concomitant non-C. difficile infection antibiotic use after the diagnosis of C. difficile infection B PPIs started during/after C. difficile infection diagnosis. B Severity assessment: Classify patients with C. difficile infection as severe at diagnosis in the presence of WBC 15,000 cells/mm or serum creatinine > 1.5 mg/dL. B Classify patients with severe C. difficile infection as fulminant in the presence of hypotension, shock, ileus, or megacolon. B 3. Diagnostic investigations History and physical examination: Elicit a disease-specific history emphasizing risk factors, symptoms, underlying comorbidities, and signs of severe or fulminant disease in patients with suspected C. difficile infection. B Assess for peritonitis and multisystem organ failure in patients with C. difficile infection. B Stool testing, sampling: https://web.pathway.md/diseases/recQxWZGEt8jznT23 3/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway As per WSES 2019 guidelines, obtain PCR testing of perirectal swabs as an acceptable alternative to stool specimen analysis in patients with ileus unable to produce stool specimens. B As per IDSA 2017 guidelines: Prefer obtaining fresh stool samples for C. difficile testing. B Obtain a single diarrheal stool specimen for the detection of toxin or a toxigenic C. difficile strain. B As per ESCMID 2016 guidelines, do not limit C. difficile infection testing to samples with a specific physician's request. D Show 4 more Stool testing, testing protocol: As per ACG 2021 guidelines, use highly sensitive and specific testing modalities to distinguish colonization from active infection. B As per ASCRS 2021 guidelines, obtain 2-step testing to increase the accuracy of C. difficile infection diagnosis. A As per WSES 2019 guidelines, consider obtaining NAATs for C. difficile toxin genes as a standard diagnostic test for C. difficile infection. Obtain NAATs as a single-step algorithm, or in a 2-step algorithm starting with toxin-enzyme immunoassays, to increase detection of asymptomatic colonization in patients with high suspicion for C. difficile infection. B Show 3 more As per SHEA/IDSA 2018 guidelines: Obtain stool toxin testing as part of a multistep algorithm (glutamate dehydrogenase plus toxin; glutamate dehydrogenase plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than NAAT alone for all specimens received in the clinical laboratory when there are no pre- agreed institutional criteria for patient stool submission. B Obtain NAAT alone or a multistep algorithm for testing (glutamate dehydrogenase plus toxin; glutamate dehydrogenase plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than toxin testing alone when there are pre-agreed institutional criteria for patient stool submission. B As per ESCMID 2016 guidelines, use a 2-step algorithm, starting with either NAAT or glutamate dehydrogenase enzyme immunoassay, for laboratory evaluation of C. difficile infection. Consider reporting samples with a negative first test result as negative. Test samples with a positive first test result further with a toxin A/B enzyme immunoassay. Report samples with a positive second test result as C. difficile infection-positive. B Show 4 more Stool testing, repeat testing: As per WSES 2019 guidelines, consider obtaining repeat testing after a first negative sample during the same diarrheal episode only in selected patients with ongoing clinical suspicion during an epidemic or in patients with high clinical suspicion during an endemic. B As per SHEA/IDSA 2018 guidelines, do not obtain repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiological https://web.pathway.md/diseases/recQxWZGEt8jznT23 4/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway studies. D As per ESCMID 2016 guidelines: Do not obtain repeat testing after the first positive sample during the same diarrheal episode in an endemic. D Consider obtaining repeated testing after a first negative sample during the same diarrheal episode in selected cases with ongoing clinical suspicion during an epidemic or in cases with high clinical suspicion during an endemic. B Biological markers: insufficient evidence to support the use of biological markers as an adjunct to diagnosis. I Diagnostic imaging: As per ASCRS 2021 guidelines, recognize that radiologic evaluation has limited utility in C. difficile infection. B As per WSES 2019 guidelines: Consider obtaining CT in patients with clinical manifestations of severe-complicated C. difficile colitis. C Consider obtaining an ultrasound in critically ill patients with suspected pseudomembranous colitis unable to be transported to the CT suite. C 4. Diagnostic procedures Lower gastrointestinal endoscopy: As per ASCRS 2021 guidelines, do not obtain a routine endoscopic evaluation to diagnose or determine the extent of C. difficile infection. D As per WSES 2019 guidelines, consider performing flexible sigmoidoscopy for the diagnosis of C. difficile colitis in case of a high level of clinical suspicion. C 5. Medical management Discontinuation of inciting antibiotics: As per ESCMID 2021 guidelines, discontinue the inciting antibiotic and closely monitor the patient for 48 hours in case of non-severe C. difficile infection. E As per WSES 2019 guidelines, discontinue unnecessary antibiotic agents in patients with suspected C. difficile infection. B As per IDSA 2018 guidelines, discontinue the inciting antibiotic agent as soon as possible, as this may influence the risk of C. difficile infection recurrence. B Discontinuation of proton-pump inhibitors: avoid discontinuing antisecretory therapy in patients with C. difficile infection, provided there is an appropriate indication for their use. D Supportive care: https://web.pathway.md/diseases/recQxWZGEt8jznT23 5/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway As per ACG 2021 guidelines, administer adequate volume resuscitation in patients with fulminant C. difficile infection. B As per WSES 2019 guidelines, ensure early detection of shock and provision of aggressive management of underlying organ dysfunction in patients with fulminant colitis. Provide supportive measures, including IV fluid resuscitation, albumin supplementation, and electrolyte replacement in all patients with severe C. difficile infection. B Antibiotic therapy, empiric therapy: As per WSES 2019 guidelines, avoid initiating empirical therapy for C. difficile infection unless there is a strong suspicion. Consider initiating empirical therapy for C. difficile infection while awaiting test results in case of a strong suspicion of severe C. difficile infection. D As per SHEA/IDSA 2018 guidelines, initiate empiric antibiotic therapy for C. difficile infection if a substantial delay in laboratory confirmation is expected, or for fulminant C. difficile infection. B Antibiotic therapy, non-severe disease: As per ACG 2021 guidelines: Administer oral fidaxomicin 200 mg BID B or oral vancomycin 125 mg QID for 10 days in patients with an initial episode of non-severe C. difficile infection. B Consider administering oral metronidazole 500 mg TID for 10 days in low-risk patients with an initial episode of non-severe C. difficile infection. B As per ASCRS 2021 guidelines, consider administering oral vancomycin or fidaxomicin as first- line therapy in patients with an initial C. difficile infection. Avoid using metronidazole alone as first-line therapy. B As per ESCMID 2021 guidelines, administer fidaxomicin 200 mg BID for 10 days in patients with an episode of C. difficile infection. B Show 5 more As per SHEA/IDSA 2021 guidelines, consider administering fidaxomicin 200 mg PO BID for 10 days rather than a standard course of vancomycin in patients with an initial episode of C. difficile infection. C Show 2 more As per WSES 2019 guidelines: Administer oral vancomycin in patients with mild-to-moderate disease not responding to metronidazole. Consider administering fidaxomicin in patients at higher risk for recurrences, such as elderly patients or patients receiving concomitant antibiotics. A Limit the use of oral metronidazole to the treatment of an initial episode of mild-to-moderate C. difficile infection. A Avoid administering repeated or prolonged courses of metronidazole due to the risk of cumulative and potentially irreversible neurotoxicity. B Antibiotic therapy, severe disease: As per ACG 2021 guidelines, administer vancomycin 125 mg QID B or fidaxomicin 200 mg BID for 10 days as initial therapy in patients with severe C. difficile infection. B https://web.pathway.md/diseases/recQxWZGEt8jznT23 6/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway As per ASCRS 2021 guidelines, consider administering oral vancomycin or fidaxomicin as first- line therapy in patients with an initial episode of C. difficile infection. Avoid using metronidazole alone as a first-line therapy. B As per ESCMID 2021 guidelines, administer vancomycin 125 mg QID for 10 days or fidaxomicin 200 mg BID for 10 days in patients with severe C. difficile infection. E Show 3 more As per SHEA/IDSA 2021 guidelines: Consider administering fidaxomicin 200 mg PO BID for 10 days rather than a standard course of vancomycin in patients with an initial episode of C. difficile infection. C Consider administering oral vancomycin 125 mg PO QID for 10 days as an alternative to fidaxomicin in patients with an initial episode of C. difficile infection. B As per WSES 2019 guidelines, administer oral vancomycin or fidaxomicin in all patients with severe C. difficile infection. Consider administering fidaxomicin in patients at higher risk for recurrences, such as elderly patients or patients receiving concomitant antibiotics. A Antibiotic therapy, fulminant disease: As per ACG 2021 guidelines, administer oral vancomycin 500 mg every 6 hours in patients with fulminant C. difficile infection. B Consider administering combination therapy with parenteral metronidazole 500 mg every 8 hours. B As per ESCMID 2021 guidelines: Administer vancomycin 125 mg QID for 10 days or fidaxomicin 200 mg BID for 10 days in patients with severe-complicated C. difficile infection. E Consider adding IV tigecycline 50 mg BID (100 mg loading dose) on a case-by-case basis when a patient is deteriorating or progressing to severe-complicated C. difficile infection while on anti-C. difficile infection antibiotic therapy. C As per WSES 2019 guidelines, administer high-dose vancomycin (500 mg every 6 hours), oral and/or by enema, in combination with IV metronidazole (500 mg every 8 hours) in patients with fulminant colitis. B As per SHEA/IDSA 2018 guidelines: Administer oral vancomycin 500 mg QID in patients with fulminant C. difficile infection. B Administer IV metronidazole 500 mg every 8 hours in addition to oral or rectal vancomycin, particularly in patients with ileus. B Antibiotic therapy, ileus: As per ACG 2021 guidelines, consider administering vancomycin enemas (500 mg every 6 hours) in addition to oral antibiotic therapy in patients with ileus. C As per ESCMID 2021 guidelines: Attempt intraluminal (gastroduodenal or coloscopic) delivery of vancomycin or fidaxomicin if oral therapy is impossible. E Consider administering adjunctive IV metronidazole 500 mg TID or IV tigecycline 50 mg two times daily (100 mg loading dose). C https://web.pathway.md/diseases/recQxWZGEt8jznT23 7/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway As per WSES 2019 guidelines, consider administering vancomycin as a retention enema via a large rectal tube or catheter if oral antibiotics cannot reach the colon. B As per SHEA/IDSA 2018 guidelines: Consider administering vancomycin per rectum (500 mg in approximately 100 mL normal saline every 6 hours as a retention enema) in addition to oral antibiotics in patients with ileus. C Administer IV metronidazole 500 mg every 8 hours in addition to oral or rectal vancomycin in patients with ileus. B Bezlotoxumab: As per ESCMID 2021 guidelines, consider administering bezlotoxumab in addition to oral standard-of-care treatment for an episode of C. difficile infection with an increased risk of recurrence if fidaxomicin is not available or feasible. Reserve bezlotoxumab use in patients with a history of congestive HF when the benefits outweigh the risk. C As per WSES 2019 guidelines, consider administering coadjuvant monoclonal antibodies (bezlotoxumab) to prevent recurrences of C. difficile infection, particularly in patients with C. difficile infection due to the 027 epidemic strain, in immunocompromised patients, and in patients with severe C. difficile infection. B Intravenous immunoglobulin: administer IVIG only as an adjunct therapy in patients with multiple recurrent or fulminant Clostridium difficile infection. B Antiperistaltic agents: discourage the use of antiperistaltic agents for the treatment of C. difficile infection. Combine antiperistaltic agents with anti-C. difficile medications if antiperistaltic agents are used to control persistent symptoms in patients with C. difficile infection. B 6. Nonpharmacologic interventions Probiotics: As per ASCRS 2021 guidelines, do not use probiotics for the treatment of C. difficile infection. D As per AGA 2020 guidelines, insufficient evidence to support the use of probiotics for the treatment of patients with C. difficile infection outside a clinical trial. I As per WSES 2019 guidelines, consider offering probiotics as an adjunctive treatment to antibiotics in immunocompetent patients with the first episode of C. difficile infection. C 7. Therapeutic procedures Fecal microbiota transplantation (setting of care): form a multidisciplinary team to deliver fecal microbiota transplantation services. B Show 2 more https://web.pathway.md/diseases/recQxWZGEt8jznT23 8/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway Fecal microbiota transplantation (pre-transplant care): counsel patients about short-term adverse events associated with fecal microbiota transplantation, particularly the possibility of self- limiting gastrointestinal symptoms, and inform them that serious adverse events are rare. B Show 7 more Fecal microbiota transplantation (initial disease): Do not perform fecal microbiota transplantation as an initial treatment for C. difficile infection. D Consider performing fecal microbiota transplantation in patients with refractory C. difficile infection. B Fecal microbiota transplantation, severe disease: As per ACG 2021 guidelines, consider performing fecal microbiota transplantation in patients with severe or fulminant C. difficile infection refractory to antibiotic therapy, particularly in poor surgical candidates. B As per ESCMID 2021 guidelines, consider performing fecal microbiota transplantation as rescue therapy in patients with severe complicated C. difficile infection deteriorating despite antibiotic treatment and if surgery is not feasible. Obtain a risk-benefit analysis of fecal microbiota transplantation and/or surgical management on a case-by-case basis and discuss by the multidisciplinary team. C As per HIS/BSG 2018 guidelines, perform fecal microbiota transplantation in patients with severe or complicated C. difficile infection only after medical treatment (fidaxomicin and bezlotoxumab). B Fecal microbiota transplantation, recurrent disease: As per WSES 2019 guidelines, consider performing fecal microbiota transplantation in patients with multiple recurrences of C. difficile infection failed appropriate antibiotic treatments. C As per HIS/BSG 2018 guidelines, perform fecal microbiota transplantation after initial fecal microbiota transplantation failure. A Consider performing fecal microbiota transplantation for recurrent C. difficile infection after a recurrence of symptoms following the resolution of an episode of C. difficile infection treated with appropriate antimicrobials for at least 10 days. B Show 2 more As per SHEA/IDSA 2018 guidelines: Perform fecal microbiota transplantation in patients with multiple recurrences of C. difficile infection failed appropriate antibiotic treatments. B Consider performing fecal microbiota transplantation in pediatric patients with multiple recurrences of C. difficile infection following standard antibiotic treatments. C Landmark trials: Fecal transplant for recurrent C. difficile colitis In patients with recurrent C. difficile infection, the combination of vancomycin regimen, bowel lavage, and duodenal infusion of donor feces significantly resolved C. difficile-associated diarrhea in 13 out of 16 patients (81%) after first infusion and 2 out of the remaining 3 in the second infusion, as compared with standard vancomycin regimen alone [4 of 13 patients https://web.pathway.md/diseases/recQxWZGEt8jznT23 9/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway (31%)] or with a standard vancomycin regimen with bowel lavage [3 of 13 patients (23%)] (p < 0.001 for both comparisons with the infusion group). There were no significant differences in adverse events among the three study groups, except for mild diarrhea and abdominal cramping in the infusion group on the day of infusion. van Nood E et al. N Engl J Med. 2013 Jan 31. Fecal microbiota transplantation (patients with comorbidities): consider offering fecal microbiota transplantation cautiously in patients with C. difficile infection and decompensated chronic liver disease. C Show 2 more Fecal microbiota transplantation (selection and evaluation of donors): view both related and unrelated donors as acceptable for fecal microbiota transplantation, but source fecal microbiota transplant ideally from a centralized stool bank, from a healthy unrelated donor, where possible. B Show 5 more Fecal microbiota transplantation (transplant material sampling and storage): process donor stool within 6 hours of defecation. B Show 8 more Fecal microbiota transplantation (transplant administration): perform colonoscopic administration of fecal microbiota transplant, preferentially delivering to the cecum or terminal ileum, B in patients with recurrent or refractory C. difficile infection. A Perform fecal microbiota transplantation via enema when colonoscopy or flexible sigmoidoscopy is not possible. A Show 3 more Fecal microbiota transplantation (post-transplant care): provide immediate management after endoscopic administration of fecal microbiota transplantation as per endoscopy unit protocol. B Show 4 more 8. Surgical interventions Indications for surgery: As per ACG 2021 guidelines, consider performing either total colectomy with end ileostomy and stapled rectal stump or diverting loop ileostomy with colonic lavage and intraluminal vancomycin in patients requiring surgical intervention, depending on clinical circumstances, the patient's estimated tolerance to surgery, and the surgeon's best judgment. C As per ASCRS 2021 guidelines, reserve surgery for patients with colonic perforation or severe colitis not improving with medical therapy. B Show 2 more As per ESCMID 2021 guidelines: Consult a surgeon for any severe-complicated case. Consult a surgeon as soon as the patient's condition is deteriorating or not responding to C. difficile infection treatment. E https://web.pathway.md/diseases/recQxWZGEt8jznT23 10/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway Consider performing partial colectomy or loop ileostomy to prevent total abdominal colectomy. C As per WSES 2019 guidelines: Obtain early surgical consultation and evaluate for potential surgical interventions in patients with severe C. difficile infection progressing to systemic toxicity. B Consider resecting the entire colon in patients with fulminant colitis. Consider performing diverting loop ileostomy with colonic lavage as an alternative to colectomy. B As per IDSA 2018 guidelines: Perform subtotal colectomy with preservation of the rectum if surgical management is necessary for severely ill patients with C. difficile colitis. B Consider performing diverting loop ileostomy with colonic lavage followed by antegrade vancomycin flushes as an alternative approach. C As per EAST 2014 guidelines: Perform surgery early before the development of shock or the need for vasopressors in adult patients with C. difficile infection. B Consider performing total or subtotal colectomy rather than partial colectomy or other surgery in adult patients with C. difficile infection eligible for surgery. C 9. Specific circumstances Pediatric patients (evaluation): do not test for C. difficile infection routinely in neonates or infants 12 months of age with diarrhea because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants. D Show 2 more Pediatric patients (antibiotic therapy): administer metronidazole 7.5 mg/kg/dose TID or QID or vancomycin 10 mg/kg/dose QID in pediatric patients with an initial episode or first recurrence of non-severe C. difficile infection. B Show 2 more Pediatric patients (fecal microbiota transplantation): consider performing fecal microbiota transplantation in pediatric patients with multiple recurrences of C. difficile infection following standard antibiotic treatments. C Pregnant patients: administer vancomycin for the treatment of pregnant, peripartum, and breastfeeding patients with C. difficile infection. B Immunosuppressed patients (antibiotic therapy): consider administering vancomycin or fidaxomicin as first-line therapy in immunocompromised patients with C. difficile infection. C Immunosuppressed patients (fecal microbiota transplantation): Offer fecal microbiota transplantation cautiously in immunosuppressed patients. B Perform fecal microbiota transplantation in immunosuppressed patients at risk of severe infection using fecal microbiota transplant only from donors negative for EBV and CMV. B https://web.pathway.md/diseases/recQxWZGEt8jznT23 11/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway Patients with inflammatory bowel disease, evaluation: As per AAST/WSES 2021 guidelines: Obtain stool toxin testing to exclude C. difficile infection in urgent clinical situations in patients with Crohn's disease. B Obtain testing for C. difficile infection in patients with a suspected IBD flare. B As per ACG 2021 guidelines, obtain testing for C. difficile infection in patients with IBD presenting with an acute flare associated with diarrhea. B As per ACG 2019 guidelines: Obtain stool testing to exclude C. difficile infection in patients with suspected ulcerative colitis. B Obtain stool testing to exclude C. difficile infection in patients with acute severe ulcerative colitis. B As per ACG 2018 guidelines, obtain stool testing for C. difficile in patients with symptoms of active Crohn's disease. E As per AGA 2017 guidelines, obtain testing for C. difficile infection in patients presenting with a flare of underlying IBD. B Patients with inflammatory bowel disease, antibiotic therapy: As per ACG 2021 guidelines, consider administering oral vancomycin (125 mg QID for a minimum of 14 days) in patients with IBD and C. difficile infection. B As per AGA 2017 guidelines, consider administering vancomycin rather than metronidazole for the treatment of C. difficile infection in patients with IBD. C Show 2 more Patients with inflammatory bowel disease, withholding immunosuppressive therapy: As per ACG 2021 guidelines, do not hold immunosuppressive IBD therapy during anti-C. difficile infection treatment in the setting of disease flare, and consider escalating therapy if there is no symptomatic improvement with treatment of C. difficile infection. D As per AGA 2017 guidelines, consider postponing the escalation of corticosteroids and other immunosuppression agents during acute C. difficile infection until therapy for C. difficile infection has been initiated. Decide on withholding or continuing immunosuppression in patients with IBD with C. difficile infection on an individual basis. C Patients with inflammatory bowel disease, fecal microbiota transplantation: As per ACG 2021 guidelines, consider performing fecal microbiota transplantation in patients with IBD and recurrent C. difficile infection. B As per HIS/BSG 2018 guidelines: Offer fecal microbiota transplantation in patients with IBD and recurrent C. difficile infection. Counsel patients about a small but recognized risk of exacerbating IBD. B Do not offer fecal microbiota transplantation for the treatment of IBD. Insufficient evidence to recommend fecal microbiota transplantation for any other gastrointestinal or non- gastrointestinal disease apart from C. difficile infection. D https://web.pathway.md/diseases/recQxWZGEt8jznT23 12/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway As per AGA 2017 guidelines, offer a referral for fecal microbiota transplantation in patients with IBD and recurrent C. difficile infection. B 10. Preventative measures Antibiotic stewardship: As per ASCRS 2021 guidelines, consider implementing an evidence-based antibiotic stewardship program to decrease rates of C. difficile infection. B As per WSES 2019 guidelines, consider implementing proper antibiotic stewardship in both selecting an appropriate antibiotic and optimizing its dose and duration to prevent and cure an infection to prevent the emergence of C. difficile. B As per IDSA 2018 guidelines: Minimize the frequency and duration of high-risk antibiotic therapy and the number of antibiotic agents prescribed to reduce C. difficile infection risk. B Implement an antibiotic stewardship program. B Discontinuation of proton-pump inhibitors: As per WSES 2019 guidelines, discontinue unnecessary PPIs in patients at high risk for C. difficile infection. B As per IDSA 2018 guidelines, insufficient evidence to recommend discontinuing PPIs as a measure for preventing C. difficile infection, although there is an epidemiologic association between PPI use and C. difficile infection. I As per ACG 2013 guidelines, prescribe PPIs with care in patients at risk of C. difficile infection. B Infection control measures, contact precautions: As per ASCRS 2021 guidelines, implement infection control measures for hospitalized patients with C. difficile infection. B As per WSES 2019 guidelines, place C. difficile carriers in contact (enteric) precautions. B As per SHEA/IDSA 2018 guidelines, accommodate patients with C. difficile infection in a private room with a dedicated toilet to decrease transmission to other patients. Prioritize patients with stool incontinence for placement in private rooms if there is a limited number of private single rooms. B Show 5 more Infection control measures, hand hygiene: As per WSES 2019 guidelines, practice hand hygiene with soap and water when contacting with patients with known or suspected C. difficile infection. B As per SHEA/IDSA 2018 guidelines, practice hand hygiene before and after contact with a patient with C. difficile infection and after removing gloves with either soap and water or an alcohol-based hand hygiene product, both in routine and endemic settings. B Show 3 more https://web.pathway.md/diseases/recQxWZGEt8jznT23 13/14 6/23/23, 3:26 AM Clostridioides difficile infection Pathway Infection control measures, equipment and room cleaning: As per WSES 2019 guidelines, perform good cleaning and disinfection of patient care equipment used in patients with known or suspected C. difficile infection. B As per SHEA/IDSA 2018 guidelines, use disposable patient equipment when possible and ensure that reusable equipment is thoroughly cleaned and disinfected, preferentially with a sporicidal disinfectant compatible with the equipment. B Show 4 more Prophylactic probiotics: As per ACG 2021 guidelines: Do not offer probiotics for the prevention of C. difficile infection in patients receiving antibiotics (primary prevention). D Do not offer probiotics for the prevention of C. difficile infection recurrence (secondary prevention). D As per ASCRS 2021 guidelines, consider offering probiotics for the prevention of C. difficile infection. C As per ESCMID 2021 guidelines, do not offer routine probiotics to prevent C. difficile infection when on antibiotic treatment. D As per AGA 2020 guidelines, consider offering probiotics with the following strains for the prevention of C. difficile infection in adult and pediatric patients on antibiotic treatment: saccharomyces boulardii a combination of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R a combination of Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidum a combination of Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium bifidum, and S. salivarius subsp. thermophilus. C As per WSES 2019 guidelines: Consider offering prophylactic probiotics to inpatients receiving antibiotics during high-risk periods (such as outbreaks) before the disease develops. Do not use probiotics in immunocompromised patients. C Consider offering probiotics as an adjunct to standard antibiotic treatment (vancomycin) to prevent recurrent episodes in patients with at least one prior episode of C. difficile infection. C As per IDSA 2018 guidelines, insufficient evidence to support the use of probiotics for primary prevention of C. difficile infection outside of clinical trials. I Landmark trials: PLACIDE In inpatients 65 years of age and exposed to 1 oral or parenteral antibiotics, microbial preparation was not superior to placebo with respect to a antibiotic-associated diarrhea. https://web.pathway.md/diseases/recQxWZGEt8jznT23 14/14