The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Clostridioides difficile Infection

Abstract

The American Society of Colon and Rectal Surgeons (ASCRS) is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop clinical practice guidelines based on the best available evidence. Although not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician considering all the circumstances presented by the individual patient. STATEMENT OF THE PROBLEM Clostridioides difficile, formerly known as Clostridium difficile, is an anaerobic, gram-positive, bacillus bacterium that can be a normal inhabitant of the human colon and is most commonly transmitted via a fecal-oral route.1 Alterations in the bacterial component of the microbiota, most often due to the use of antibiotics, can lead to ecological changes that select for both population growth of C difficile as well as the induction of pathogenic behavior.2,3 Although the number of patients with C difficile infection (CDI) in the United States appears relatively stable over the past decade (estimated 476,400 cases in 2011 associated with 29,000 deaths and 462,100 cases in 2017 associated with an estimated 20,500 deaths), the prevalence of the disease remains high.3–5 Although the bacterium is present in the stool of approximately 3% of healthy adults, up to 50% of those exposed to an inpatient facility may be asymptomatic carriers.5–8 Higher rates of CDI have been reported in patients after exposure to a prolonged duration of antibiotics including perioperative antibiotics and in patients with underlying comorbid conditions such as IBD or immunosuppression.9–15 Clinical manifestations of C difficile can range from an asymptomatic carrier state to mild CDI to severe, fulminant, life-threatening infection. Although descriptions of presentation and severity of disease vary in the literature, commonly used definitions are included in Table 1.16–19C difficile infection most commonly involves the colon, where it can manifest with pseudomembranes covering the colonic mucosa (“pseudomembranous colitis”). In rare circumstances, CDI may also involve the small bowel.20,21 In the early 2000s, predominantly in North America, but also in Europe, there was an increased incidence of more severe CDI due to the emergence of certain bacterial strains (ie, ribotypes) like the BI/NAP1/027/toxinotype III strain, which is associated with a life-threatening infection.22–25 Although rates of infection with this “hypervirulent” strain recently decreased in North America, rates remain significant globally.26,27 TABLE 1. - Terminology associated with Clostridioides difficile Term Definition Antibiotic-associated diarrhea Diarrhea in an individual who is currently taking or has recently taken antibiotics (not necessarily from C difficile, although C difficile is a cause of this type of diarrhea)Symptoms include watery diarrhea and abdominal cramping Asymptomatic colonization/carrier Patients colonized with C difficile without signs or symptoms of CDI C difficile infection (CDI) Presence of diarrhea characterized by >3 watery stools per day in the setting of positive C difficile testingOther symptoms can include fever, abdominal pain, cramping, nausea, and loss of appetiteHigher-risk patients include elderly or immunocompromised patients, nursing home residents, and patients with severe underlying comorbidities who have been exposed to antibiotics Pseudomembranous colitis Presence of plaque formations on colon mucosaConsidered pathognomonic for CDI in the appropriate clinical setting Mild/nonsevere infection CDI with leukocyte count <15 × 103/µL and creatinine <1.5 mg/dL Severe infection CDI with leukocyte count >15 × 103/µL or renal failure with creatinine >1.5 mg/dL Severe-complicated/fulminant disease CDI with hypotension, sepsis, shock, ileus, or megacolon or requiring intensive care unit care Toxic colitis CDI with extreme inflammation and dilation of the colon resulting from severe colitisCan present with abdominal distension and pain, fever, dehydration, sepsis Recurrent CDI Recurrence of symptoms with a positive stool test within 8 weeks after the completion of a course of CDI therapy with resolution of symptoms Refractory CDI More than 3 loose/watery stools per day with positive stool toxin assay despite appropriate therapy CDI = Clostridioides difficile infection. A variety of practice measures and collaborative efforts have been implemented to reduce the rate of CDI and have had moderate success.18,19,28–32 The combination of antibiotic stewardship programs and improved diagnosis and treatment have decreased the incidence and mortality rates of CDI; however, CDI continues to be a source of morbidity and mortality due in part to a rise in recurrent and resistant infections.33–37 The relatively high incidence of CDI and the significant economic burden of certain infection control measures, such as “deep cleaning” of hospital rooms, requires a careful balance between prevention and cost.21,38–41 Although several guidelines have been published on this subject, CDI presents a unique challenge in colon and rectal surgery.17,18,20,42,43 This clinical practice guideline focuses on the evaluation, management, and prevention of CDI. METHODOLOGY These guidelines were developed on the platform of the previously published Practice Parameters for the Management of Clostridium difficile Infection published in 2015.42 An organized, systematic search of MEDLINE, PubMed, EMBASE, Web of Science, and the Cochrane Database of Collected Reviews was performed between September 1, 2014 and September 20, 2020. Key word combinations included “Clostridium difficile,” “Clostridioides difficile,” “Clostridia,” “colitis,” “pseudomembranous colitis,” “antibiotic-associated,” “diarrhea,” “cdiff,” “vancomycin,” “flagyl,” “metronidazole,” “rifaximin,” “antibiotics,” “colectomy,” “ileostomy,” “lavage,” “toxin,” “toxin binding,” “fecal transplant,” “probiotics,” “transmission,” “recurrence,” “recalcitrant,” “treatment,” “length of therapy,” “perforation,” “fulminant,” “prophylaxis,” “prevention,” and “megacolon.” Although the search was not limited by language, only abstracts and reports with human subjects were included. Emphasis was placed on prospective trials, meta-analyses, systematic reviews, and practice guidelines. Peer-reviewed and were included was from were performed in In were after and these abstracts were were and a of were of which were due to the of and a of were included in the The source was for the was and a treatment guideline was by the for this The of and of for were the of and there was regarding the or or treatment was from the committee and of the Clinical Practice Guidelines Committee in of these guidelines from to by the were by the Clinical Practice Guidelines Committee as well as by an and an disease The was by of the Colon and the were by the In Clinical Practice is was for this and the have related to this This guideline to the of Guidelines for and TABLE - The and quality of and or without or from can to most patients in most circumstances without and or with or or from can to most patients in most circumstances without or quality and or or but may available with and without or from best may on circumstances or or with and with or or from best may on circumstances or or or quality in the of and and burden may be or may be = of and = from of and quality of in clinical from an American of with search 1. CDI is a should be performed underlying and signs of severe or of based on related to CDI from the of bacterial that cause inflammation of the colonic mucosa and resulting in diarrhea and manifest after antibiotic therapy for disease but can be for up to 3 after of The for CDI is antibiotic use 3 and increased duration of exposure and number of antibiotics used are associated with for Although most antibiotics can the colonic bacterial to such as with and are more commonly associated with for CDI include with a health care facility as an inpatient or an CDI was a infection due to or in an care however, an of CDI has been as which may be associated and health care facility for CDI are not well but to be to CDI and include and antibiotic as include IBD and comorbidities renal and and with and are also for The clinical presentation of CDI from mild diarrhea to colitis associated with a that in than of patients and may be associated with abdominal or severe ileus, dehydration, or difficile diarrhea is characterized by watery stools 3 or more a day without or In patients who do not these of symptoms should not be for CDI. This patients with a for disease who present with an or megacolon and patients with an significant may from a C difficile Although C difficile most commonly a reports in the small as In all of these significant disease was in patients with an and was associated with patients with a of a prolonged antibiotic or or a of or not the for CDI remains of and a from antibiotic A of patients from the that (ie, including and antibiotic decreased rates of in with patients who were reported by in a of patients who only to the In this patients had rates of CDI than patients who not a = a of patients with colon who were to with or without antibiotics in the rates of CDI between the In a of demonstrated an increased of CDI related to the use of antibiotics but the incidence of CDI was the clinical of these This that the incidence of CDI after is of the used the demonstrated of related to a in the regarding CDI is not to in these Patients should be to the severity of CDI and for the of or of based on In it is to CDI severity on the of and Clinical and count and renal and are performed to the patient and to failure and associated A significant the for CDI but is not The of the severity of CDI as severe, or is and is based on and than × and abdominal with positive for C difficile in the of or failure such as is as mild severe CDI an creatinine or over × In or patients may develop abdominal and sepsis, clinical or The of to of the of with stool to the diagnosis of CDI because mortality rates from severe CDI can or failure is of the of mortality for C difficile of of a clinical clinical and stool can appropriate severe sepsis and associated The diagnosis of CDI should include stool and should be to of based on high-quality stool is the most to CDI. More than of diarrhea is to the of obtaining stool to for The of is to CDI in a and to treatment and and to and are currently available to CDI. of the specific that only watery or stool (not or be because patients with stool are to have CDI and can positive and assay by that do not the of the (ie, are not or test has a high and to between an asymptomatic carrier and is for and specific for C difficile (ie, These are and in and a and of than An to toxin in the these were and however, have these as In a positive or is by a specific test for C difficile An both to diagnosis but is associated with In where or is not may be but the should be in the of and symptoms of although not between infection and the of several strains of Clostridioides that may in stool are also they are for clinical use in Although stool is most appropriate patients with a of high rates of asymptomatic to 50% of patients in and care have for however, these have not been by the may be for patients with a but without a high for CDI who have had exposure to antibiotics or have renal or a or who in a care to or the of CDI is not of based on may be performed patients with but the of and the of these also a in or therapy or the and specific stool used to the of in this setting is limited to information conditions the diagnosis or unique circumstances a more with may CDI from of such as and Although in the setting of CDI (ie, to the may a more severe the of disease is to patient management or the for and of In often pathognomonic for are in only approximately to of cases of CDI and or In of the prevalence of pseudomembranes in the setting of the pseudomembranes are and include only a of patients with CDI who have that the incidence of pseudomembranes be than reported in these The of pseudomembranes in patients with CDI who are or have IBD is in the setting of CDI is not because of the of like and the limited clinical has limited in the setting of CDI. of based on In has limited patients with CDI. Although of the and often as part of the of an abdominal are specific for the of in the setting of CDI is in patients with CDI can colonic and an or an mucosa over with between however, these are from patients with CDI may also or of the of the colonic and or The for to the for is and that with the clinical severity of In about of patients with CDI have a normal without of A of patients with CDI that and dilation demonstrated on were associated with the for was an of however, these had a of Management Infection control measures should be implemented for patients with CDI. of based on the colon in the setting of and C difficile in (ie, form that is to the colon, however, C difficile in a form that is resistant to and In a hospital C difficile can from like or and can also by with of and prevention of on patient the use of and with and to from the of after patient commonly used in health care do not and should not be used as a for these and with and is to of CDI in hospital and care and (ie, after patients are of can also of methods of C difficile or including and changes in hospital are not by The duration for and to patients of CDI obtaining remain and vary between In for patients CDI treatment after of diarrhea may be an antibiotic stewardship can rates of CDI. of based on use is the for and the and use of antibiotics, in have been well to the of have been implemented in the United States and with the of appropriate antibiotic use and duration of treatment in an to Although antibiotic stewardship programs vary between most include by disease and have in significant in antibiotic A Cochrane by of that with in patients the duration of CDI treatment by and CDI rates up to to include to associated antibiotics CDI has been as and the use of difficile treatment the duration of antibiotics for to In of to reduce CDI have been although they remain a 3 the of a but the was because a demonstrated that the clinical or is treatment for an is appropriate treatment. of based on high-quality Although antibiotics have demonstrated for or severe or is therapy a has been to have CDI and rates CDI than however, have the use of this as a antibiotic therapy to C difficile, it is to also the antibiotics associated with the C difficile as as circumstances because these antibiotics can the of CDI the is a day and the is a a course of CDI diarrhea in of TABLE - for and recurrent C difficile infection a day or a day for Severe as an treatment for patients or a day and 3 a day patients with ileus, per was used a day for Severe for was used for or prolonged with and was used use prolonged with and as an treatment for patients or a day and 3 a day patients with ileus, per or is course of by Severe as an treatment for patients is not prolonged with and or or or a day and 3 a day for patients with ileus, per = including the Clinical Practice or as treatment by the severity of with used for more mild disease and for more severe Although a number of with treatment for patients with mild there has been a rise in C difficile over the past In to currently has a of CDI treatment including and with therapy with both and is associated with a rate of with and is not patients have or the in the antibiotic a Cochrane by of including patients that was more in a than A by also that was to in both rate = and rate = and that the of was more in patients with moderate to severe via can be as an treatment for patients with or or CDI. patients with moderate to severe CDI with and with patients who In this the that more but had mortality with the therapy although the had more severe disease and had rates of intensive care unit and reported a patients who in to therapy with patients who treatment and in A systematic by and that the of therapy is and and a of in Although a reports a to colon, these reports include relatively patients, and do not this a is in use of antibiotics to CDI although patients may be in but not in CDI. of based on high-quality of can the colonic bacterial and an that to the of CDI. are and well but the regarding the of in the treatment and prevention of CDI are and systematic demonstrated significant in of CDI treatment or More meta-analyses, however, but not from A of with patients demonstrated a incidence of CDI associated with the use of of including patients demonstrated that decreased the of C difficile diarrhea by the included in this were and reported and An including Cochrane that the of reported a decreased incidence of diarrhea and CDI related to the quality of the the that should be reports specific strains or combinations of including and and do not a regarding regarding the of and remain The of in recurrent or CDI is in for C difficile colitis should be for patients with colonic or severe colitis who do not with of based on Although the incidence of and mortality from CDI have been over remains an part of the treatment because approximately of all patients with CDI and about of patients with or disease In the most for in the setting of CDI is in rare cases of colonic the to with is to because there is to which patients to management and surgery. have clinical that can patients who are more to including patients with or Although there is regarding the of it appears that in the course of disease is the circumstances, these patients may have and In it is to that IBD is a significant for CDI and for requiring and used to these patients, have been to be for in patients with IBD and in a by patients with colitis had the of a in the setting of CDI with is the procedure for or C difficile of based on The procedure for or C difficile colitis is with and because this source control in the the of mortality after an (ie, or than after a however, these are limited by small and In a systematic and in patients with CDI between and as of most of or the with was the most commonly performed procedure In this the to a was due to a colon on because C difficile colitis is a a of the and severity of disease be made by the of the with was not to colon was in of patients of and high mortality these continues to be performed in the States these In of therapy after the not a specific for antibiotics after for rates for CDI are high and can range from to despite the high mortality associated with several have reported improved for patients with C difficile colitis who with management A systematic of patients with C difficile colitis also demonstrated a with abdominal with The most reported of mortality after for CDI include patient like or and clinical signs of such as or to several mortality that for in the setting of patients who are and in therapy has but who have not are more to after Although is can reduce the for and of are and on the specific after for CDI remain with a of a of and a rate of A with colonic may be an to for the treatment of or CDI. of based on with remains the treatment for patients with an a and colonic antibiotic has been of this the high mortality in patients with for or C difficile as well as the morbidity from an that may be The of colonic these circumstances the In this involves of a by colonic with via the and of as well as An prospective and colonic for CDI patients with CDI who colonic and with mortality with 50% mortality in a control with of the patients a and had with only in the control A patients with and colonic or and decreased mortality in the = with the = = A by patients who with colonic with patients who and that therapy for colon and of in most patients, but not mortality or the rate of recurrent CDI. and therapy for CDI include an of the American of Surgeons that patients who with patients who had abdominal and a rate in the = but and from the patients who had a with patients who abdominal and significant in including mortality between the A that included patients with and patients with abdominal in mortality and although rates of were in the Recurrent and Refractory CDI A prolonged course of or is an therapy for recurrent or CDI in stable of based on Recurrent and disease can the management of patients with CDI. Recurrent infection within 8 weeks of treatment for an and rates range from to the of mortality from recurrent disease from to for CDI include antibiotic use after treatment for use of and infection with certain C difficile Although not several are for recurrent CDI the of the antibiotic on the therapy used for the in patients are not by the same a to course of is used for the the should be with a and or a course of and include a to course of a of per day by a over weeks by with or 3 for to 8 may be used despite the of use over is used for an the can be with a to course of a that by the and to be with treatment of can the of in patients due to or 3 the of to antibiotic and and demonstrated that treatment with decreased rates of recurrent CDI with a of an antibiotic course for CDI demonstrated a for recurrent CDI and a in hospital of the of may be use in these Patients with recurrent or CDI should be for measures, including appropriate antibiotic have of based on with 3 or more CDI can be with a and course or by a therapy such as trials, systematic reviews, and that patients with recurrent or CDI in treatment has should be for In antibiotic treatment should be used for (ie, 3 CDI In of the have CDI rates after performed with and the significant with which have been for have been Although a number of methods of have been including a or the most is via however, were to be to for recurrent rates for of the are reported to be between and after a has been in certain and has been to be in and patients and in patients with IBD or patients who develop recurrent CDI after an the and has been an of failure after by in the setting of recurrent CDI include severe CDI and of this treatment is to patient and of the A of regarding is this as a therapy for A = with therapy = and that may be an to antibiotics in this The of in patients with severe CDI has not been reports and small that may be and in the for in patients to but the is have been reports of and prospective should be for with in to more In in to deaths in patients, the and a the of obtaining proper patient including a regarding related to the including and may be in to treatment in cases of recurrent or CDI. of based on In where antibiotic therapy for recurrent CDI can be may be used to recurrent CDI and has a moderate rate in this because of the of C difficile to develop to this should be used in combination with for can strains of C difficile by for In a of cases of CDI with antibiotics with patients and were an is therapy for recurrent or such as and are also used as for recurrent CDI with reports for these to and C difficile however, prospective have not demonstrated in symptoms or can also on in the of these should be by a regarding a developed to C difficile A and it is to and for but as an therapy is to patients with CDI has been because this therapy has been associated with however, prospective regarding this practice is not may be in recurrent or but the of these circumstances remains used in combination with appropriate therapy were to the of recurrent disease in a but 3 not a to these

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