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What’s New in the Patient Safety World

August 2021

Updated Guidelines on C. diff



The American College of Gastroenterology has updated guidelines on prevention, diagnosis, and treatment of C. diff (Kelly 2021), its first update since 2013. Though we’ll always continue to refer to it as C. diff, the guidelines acknowledge the name change to Clostridioides difficile (it was formerly named Clostridium difficile). Overall, they make 23 GRADED recommendations for the management regarding C. diff.


While there had been a substantial increase in C. diff incidence over the first decade of this century, the estimated national burden of C. diff infection and associated hospitalizations decreased from 2011 through 2017, owing to a decline in health care–associated infections (Guh 2020). C. diff burden in long-term care facilities also saw a decrease. These suggest that efforts at reducing CDI in hospitals and other healthcare facilities have been successful.


Perhaps the most important change in the updated guidelines is inclusion of fecal microbial transplant (FMT) as a treatment for C. diff infection (CDI). But the guidelines also include new recommendations on diagnostic testing, and use of bezlotoxumab in prevention of CDI recurrence.


The guidelines cover management of all levels of severity of C. diff, from asymptomatic colonization to severe infection. Criteria for definitions of “severe” and “fulminant” CDI are included in the guideline.


Differentiating colonization from infection has been improved with adoption of new testing capabilities. The guideline notes that only individuals with symptoms suggestive of active CDI should be tested (3 or more unformed stools in 24 hours). A two-step diagnostic process is now recommended, with stool being first tested using a test with high sensitivity, such as nucleic acid amplification testing or glutamate dehydrogenase, and then followed by highly specific enzyme immunoassay.


For nonsevere CDI, either oral vancomycin or oral fidaxomicin are recommended, though the guideline also notes oral metronidazole may be used in low-risk patients.


For severe CDI, 10 days of oral vancomycin or oral fidaxomicin is recommended.


For fulminant CDI, oral vancomycin plus fluid resuscitation is recommended. Adding parenteral metronidazole is noted as an option, though the guideline notes the level of evidence for this is of low quality.


See the guideline itself for the recommended doses of the various antimicrobials in each situation discussed.


The major update is use of fecal microbial transplant (FMT) in cases of severe or fulminant CDI that are resistant to antibiotics. FMT is also now used to prevent recurrence in patient at high risk.


Prevention/prophylaxis is also discussed. Oral vancomycin prophylaxis can be used when patients with a history of CDI undergo subsequent use of systemic antibiotics. As noted above, fecal microbial transplant (FMT) can be used to prevent recurrence in patient at high risk (and may need to be repeated one or more times). Another new recommendation is for use of the monoclonal antibody bezlotoxumab for prevention of CDI recurrence in patients at high risk of recurrence.


Note that the guideline recommends against use of probiotics either in prevention of recurrent CDI or as prophylaxis in patients on antibiotic therapy, citing lack of strong evidence.


The guideline also includes recommendations for special circumstances, such as pregnancy and lactation, inflammatory bowel disease, immunocompromised states, and patients requiring surgical intervention.


We should note that there have been several other good reviews of C. diff management in recent years (Wilcox 2019, Rao 2020, Cho 2020).


The new ACG guidelines did not to make GRADE recommendations regarding infection control and prevention. Instead, they pointed to other published guidelines having comprehensive recommendations for preventing CDI. They note that clinical practice guidelines from the IDSA/SHEA and European Society of Clinical Microbiology and Infectious Diseases recommend isolating patients with suspected or confirmed CDI, use of full barrier precautions (i.e., gowns and gloves) while caring for these patients, and hand hygiene before and after contact with patients with CDI, preferably using soap and water. They note that none of these guidelines recommend contact precautions in asymptomatic carriers. They do stress use of antibiotic stewardship programs that restrict high risk antimicrobials and minimize unnecessary antimicrobials to control rates of CDI.


Barker et al. (Barker 2020) evaluated the cost-effectiveness of infection control strategies to reduce hospital-onset C. diff infection. Interventions considered included daily sporicidal cleaning, terminal sporicidal cleaning, health care worker hand hygiene, patient hand hygiene, visitor hand hygiene, health care worker contact precautions, visitor contact precautions, C difficile screening at admission, and reduced intrahospital patient transfers. Their evaluation suggests that institutions should seek to streamline their infection control initiatives and prioritize a smaller number of highly cost-effective interventions. Daily sporicidal cleaning was among several cost-saving strategies that could be prioritized over minimally effective, costly strategies, such as visitor contact precautions.


Lastly, one problem not discussed in the updated AGS guideline is that of overtesting for C. diff. Dunn et al. (Dunn 2020) did a systematic review of studies evaluating the association between clinical decision support (CDS) alerts for CDI diagnosis and CDI testing volume and/or CDI rate. They conclude that the use of electronic alerts for diagnostic stewardship for C. difficile was associated with reductions in CDI testing, the proportion of inappropriate CDI testing, and rates of CDI in most studies. But they also noted that broader concerns related to alerts remain understudied, including unintended adverse consequences and alert fatigue.


It’s pretty clear that considerable progress has been made on reducing the burden of C. diff on our patients and our healthcare system.





Since we initially wrote this column, IDSA (Infectious Diseases Society of America) and SHEA (Society for Healthcare Epidemiology of America) published their 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults (Johnson 2021).


The guidelines are fairly similar, though there are a few somewhat controversial differences (Willingham 2021). Probably the biggest difference iin the choice of antimicrobial for an initial episode of C. diff infection. The IDSA/SHEA guideline update makes a “conditional” recommendation for use of fidaxomicin as first preferred choice over vancomycin. It states this recommendation is based upon efficacy and safety, with a moderate certainty of evidence, but notes “its implementation depends on available resources" (the cost of  fidaxomicin is considerably higher than that for vancomycin). It does list vancomycin as an acceptable alternative.


The IDSA/SHEA guideline update also recommends fidaxomicin over a standard dose of vancomycin for recurrent CDI (again, a conditional recommendation, based on low certainty evidence). For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.


Another conditional recommendation is for patients with a recurrent CDI episode within the last six months.  The IDSA/SHEA guideline update suggests using bezlotoxumab as a co-intervention along with standard of care antibiotics rather than standard of care antibiotics alone. It makes this recommendation despite a very low certainty of evidence and it does note both cost and access issues to this monoclonal antibody.


Read the guideline update itself for discussion on the rationale and recommendations for further research on each of these 3 conditional recommendations.





Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clinical Infectious Diseases 2021; Published: 24 June 2021



Willingham E. Clostridioides difficile: 2 Sets of Guidelines Disagree. Medscape Medical News 2021; July 07, 2021







Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116(6): 1124-1147,_Diagnosis,.12.aspx



Guh AY, Mu Y, Winston LG, et al. Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes. N Engl J Med 2020; 382:1320-1330



Wilcox MH. Updated Evidence for Optimal Management of CDI . IDSE In fectious Disease Special Edition 2019; December 5, 2019



Rao K, Malani PN. Diagnosis and Treatment of Clostridioides (Clostridium) difficile Infection in Adults in 2020. JAMA 2020; 323(14):1403-1404



Cho JM, Pardi DS, Sahil K. Update on Treatment of Clostridioides difficile Infection. Mayo Clinic Proceedings 2020; 95(4): 758-769



Barker AK, Scaria E, Safdar N, Alagoz O. Evaluation of the Cost-effectiveness of Infection Control Strategies to Reduce Hospital-Onset Clostridioides difficile Infection. JAMA Netw Open 2020; 3(8): e2012522



Dunn AN, Radakovich N, Ancker JS, et al. The Impact of Clinical Decision Support Alerts on Clostridioides difficile Testing: A Systematic Review. Clinical Infectious Diseases 2021; 72(6): 987-994 Published online February 15, 2020






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