38. Johnson S, et al. ANNE MOUNSEY, MD; KELLY LACY SMITH, MD; and VINAY C. REDDY, MD, MPH University of North Carolina School of Medicine, Chapel Hill, North Carolina, SARAH NICKOLICH, MD, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania. Goldenberg JZ, Clostridium difficile infection: early history, diagnosis and molecular strain typing methods. Transmission of C. difficile most likely occurs by person-to-person contact via the fecal-oral route or by direct exposure from the contaminated environment. A 2017 Cochrane review of 39 studies found moderate evidence that probiotics are effective for preventing C. difficile–associated diarrhea, but only in trials where the C. difficile event rate was more than 5%.38 In these studies, probiotics had a number needed to treat of 12 to prevent C. difficile–associated diarrhea. Pugh MJ, 26. 18. Antibiotic stewardship that targets restriction of high-risk antibiotics can help control outbreaks and reduce infection rates; multiple studies have shown reductions of 33% to 90%.6 Similar to inpatient management, outpatient management relies on implementing an antibiotic stewardship program and minimizing the frequency and duration of antibiotic therapy, as well as the number of antimicrobial agents used. Micielli RL, Efficacy of fidaxomicin versus vancomycin as therapy for, Hu MY, Antibiotics for fulminant colitis include enteral vancomycin and parenteral metronidazole.8 If there is no clinical improvement within three to five days, fidaxomicin can be added. Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections [published correction appears in Clin Infect Dis. Epidemiology of, Shaughnessy MK, Zmora N, Schroeder MS. Dendukuri N, Zilberman-Schapira G, Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands. Impact of revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America clinical practice guidelines on the treatment of Clostridium difficile infections in the United States. Kothari D, From 2001 to 2012, the incidence of such cases increased 188.8%.15 Recurrences are likely due to treatment failure rather than reinfection with a different strain of C. difficile.16, C. difficile infection is characterized by a wide range of symptoms, from mild or moderate diarrhea—often mucoid stool with minimal blood—to severe disease with pseudo-membranous colitis, colonic ileus, toxic megacolon, sepsis, or death. et al. August 16, 2018. %���� Emerg Infect Dis. endobj Cell. Am Fam Physician. et al. Staley C, et al. Johnson JW, Kyne L, Winslow BT, OPT-80-004 Clinical Study Group. ; 23. During the same period, health care facility–acquired infections decreased from 74% to 53% of cases. et al. Zilberman-Schapira G, Once spores are in the colon, they germinate to their fully functional vegetative, toxin-producing forms and become susceptible to antibiotics. Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of, Jabbar U, Rood JI, Fidaxomicin versus vancomycin for infection with, Khoruts A, Defining the vulnerable period for re-establishment of. Wu Q, EIA = enzyme immunoassay; GDH = glutamate dehydrogenase; NAAT = nucleic acid amplification test. 2011;53(5):440–447. 20. 2013;57(5):2326–2332. Emerging Infections Program C. difficile Surveillance Team. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Clin Microbiol Infect. 2010;340(3):247–252. Rokas KE, Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. 2013;56(4):615–616. Contagion, October 2020 Supplement, Fecal microbiota transplantation (FMT) is rapidly gaining interest and acceptance as a treatment for Clostridioides difficile infection. Address correspondence to Anne Mounsey, MD, University of North Carolina School of Medicine, 590 Manning Dr., Chapel Hill, NC 27514 (email: Bartlett JG. Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. et al. Fecal microbiota transplantation is recommended for patients with multiple recurrences of C. difficile infection in whom appropriate antibiotic therapy has been ineffective. C. difficile colonizes the large intestine and releases two potent exotoxins that mediate colitis and diarrhea. Guerrero DM, Ann Intern Med. Immediate, unlimited access to all AFP content. Johnson S, Zmora N, Clostridium difficile is a common health care–associated infection in the United States with an increasing incidence of community-acquired disease that can be very severe and has a … Your doctor may prescribe vancomycin (Vancocin HCL, Firvanq) or fidaxomicin (Dificid).Metronidazole (Flagyl) m… Gerding DN, 16. Johnson S, et al. 21. Clostridium difficile hospitalizations 2011–2015. 2019;111:537–547. N Engl J Med. Clin Microbiol Infect. J Hosp Infect. 2018;66(7):987–994. Clinical practice guidelines for, infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Lytvyn L, Clostridioides (formerly: Clostridium) difficile infection (CDI) is a major cause of diarrhoea for inpatients as well as outpatients. 40. Moineddin R, 7. <> Multiple randomized trials have shown cure rates ranging from 70% to 90%.6 Fecal microbiota transplantation is less effective in patients with underlying inflammatory bowel disease.27 It is generally safe but has mild to moderate self-limited adverse events (e.g., abdominal discomfort).28 Rare potential complications include aspiration, upper gastrointestinal bleeding, and colonic perforation.28 Long-term consequences are unknown.6, Patients with severe C. difficile infection or fulminant colitis should receive immediate antibiotic therapy, supportive care, and close monitoring in a hospital setting. 32. 22. 37. Any antimicrobial agent can cause C. difficile infection, but clindamycin is the most common (Table 1).4,5 Other risk factors include severe illness, being older than 70 years, gastric acid suppression, enteral feeding, gastrointestinal surgery, small bowel obstruction, obesity, hematopoietic stem cell and solid organ transplantation, inflammatory bowel disease, cirrhosis, being peripartum, chronic kidney disease, hyperglycemia, hypoalbuminemia, and leukocytosis 6,7  (Table 27). 1 0 obj Planche T, Crump JA, endobj Don't miss a single issue. Yap C, 2010;1(1):58–64. Strength of recommendation/quality of evidence, Adapted with permission from McDonald LC, Gerding DN, Johnson S, et al. Kelly CP, 3. The addition of intravenous metronidazole to oral vancomycin is associated with improved mortality in critically ill patients with Clostridium difficile infection. Johnson JW, Copyright © 2020 American Academy of Family Physicians. Effectiveness of routine patient bathing to decrease the burden of spores on the skin of patients with, Oughton MT, Eckert C, For an initial episode of nonsevere C. difficile infection, oral vancomycin or oral fidaxomicin is recommended. 12. Over the 11-year study, the proportion of community-acquired cases not associated with antibiotic use increased steadily, eventually exceeding the number of cases associated with antibiotic use. Winslow BT, Prospective derivation and validation of a clinical prediction rule for recurrent, Bakken J. Burant CJ, Author disclosure: No relevant financial affiliations. Lyras D. 2018;66(7):992. Clinical practice guidelines for, Rao K, Krakower D, Ann Intern Med. Probiotics for the prevention of. Clostridium difficile infection and patient-specific antimicrobial resistance testing reveals a high metronidazole resistance rate. Winston LG, Clin Infect Dis 2020 … Risk factors include recent exposure to health care facilities or antibiotics, especially clindamycin. et al. Barkin JA, et al. Leischner J, On February 15th, an updated clinical practice guideline for Clostridium difficile infections (CDI) was published online in the journal Clinical Infectious Diseases. Other efforts to reduce C. diff CDC is working with the Centers for Medicare and Medicaid Services (CMS) and other federal partners to reduce C. diff infections by 30% by 2020. Healthcare Cost and Utilization Project. Epidemiology of Clostridium difficile-associated infections. 2014;9(8):e105454. Guideline updates released in 2018 reflect notable changes in treatment … Approximately 25% of patients treated with vancomycin for C. difficile infection have at least one additional episode.26  Treatment options for the first recurrence include vancomycin if metronidazole was used for the initial episode, or if a standard vancomycin regimen was used for the initial episode, either fidaxomicin or a prolonged vancomycin taper followed by pulsed vancomycin (Table 4).6, There are several treatment options for patients who have had multiple recurrent episodes of C. difficile infection and have received appropriate antibiotic therapy for at least three episodes (Table 4).6 Vancomycin can be given, either in a tapered and pulsed regimen or four times per day for 10 days followed by rifaximin (Xifaxan) three times per day for 20 days. The use of probiotics for the prevention of C. difficile infection and, more specifically, C. difficile–associated diarrhea has also been examined. 27. C. difficile colonizes the human intestinal tract after the normal gut flora has been disrupted (frequently in association with antibiotic therapy) and is the causative organism of antibiotic-associated diarrhea and pseudom… Continuing treatment with the antibiotic presumed to have caused the infection prolongs diarrhea and increases the risk of treatment failure and recurrent infections,30–32 so the antibiotic should be stopped, if possible, or switched to another agent that is less likely to cause C. difficile infection. et al. The reference tests with which other assays are compared include cell cytotoxicity neutralization assay and toxigenic culture, both of which have relatively long turnaround times and are thus rarely used in clinical practice. Clin Infect Dis . Crobach MJ, The Centers for Disease Control and Prevention provides guidance for cleaning products and for preventing contamination of medical equipment (https://www.cdc.gov/infectioncontrol). Micielli RL, 1 The comprehensive clinical practice guideline addressing the epidemiology, diagnosis, treatment… Jury LA, Crook DW, Meta-analysis of antibiotics and the risk of community-associated, McDonald LC, Clostridioides difficile Infection: Update on Management. Rank KM, endobj Mody RK, 2009;136(4):1206–1214. et al. The EIA for toxins A and B has the highest specificity, whereas NAAT is both sensitive and specific. Clostridium difficile–associated diarrhea. Lawson KA, 1 Since publication of a review of the diagnosis and management of CDI in adults, 2 new clinical tests and therapies have become available and clinical practice guidelines … Kim SK. Schutze GE, 3 0 obj Clinical risk factors for severe, Reveles KR, Clinical practice guidelines for, Henrich TJ, Surveillance for community-associated, Barbut F, Katchar K, et al. Cornely OA, fidaxomicin (Dificid) are preferred over metronidazole for initial episodes of C. difficile infection. Suez J, Choose a single article, issue, or full-access subscription. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). 2008;57(13):340–343. et al. Infection control requires a robust surveillance system to detect increased infection rates or outbreaks of C. difficile infection; in addition, key preventive strategies include use of contact precautions, good hand hygiene, environmental cleaning and disinfection, and patient bathing. 29. Patients who have delayed passage of oral antibiotics due to an ileus can be given intracolonic vancomycin rectally via retention enema every six hours with or without intravenous metronidazole every eight hours.29 Monitoring serum creatinine levels is important while using high doses of vancomycin, especially if the patient has underlying chronic kidney disease. Treatment depends on whether the episode is an initial vs. recurrent infection and on the severity of the infection based on white blood cell count, serum creatinine level, and other clinical signs and symptoms. Beardsley JR, Daneman N, Published 1 June 2013 Last updated 6 September 2019 — see all updates Fisman DN, et al. 2016;22(suppl 4):S63–S81. et al. Clostridium difficile—more difficult than ever [published correction appears in N Engl J Med. McDonald LC, Gerding DN, Johnson S, et al. 2018;46(4):431–435. Jury LA, 28. 2017;65(12):1963–1973. 2011;32(3):201–206. 2015;372(24):2369–2370. et al. Berland D, Cornely OA, 41. Cochrane Database Syst Rev. Katchar K, Lawson KA, 2014;59(6):858–861. Onysko M, Shaughnessy MK, Reveles KR, Taminiau B, Common questions about Clostridium difficile infection. A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. Changes in Testing For example, new data published in The New England Journal of Medicine underscore the shortcomings of advances in testing technology, suggested Sahil Khanna, MBBS, an associate professor of medicine at Mayo Clinic College of Medicine and Science, in Rochester, Minn. (2020… et al. 2009;15(3):415–422. This clinical content conforms to AAFP criteria for continuing medical education (CME). C. diff guidelines and prevention resources for clinicians. <>>> Sambol SP, Probiotic supplements might not be universally-effective and safe: a review. Fishman EK. The risk of C. difficile infection associated with hospitalization is attributed to colonization rates of 20% to 40% in hospitalized adults compared with 2% to 3% in healthy adults.1 However, infection can occur in patients with no risk factors.9, Asymptomatic colonization is common in children, especially infants.6 Up to 63% of healthy neonates are colonized with C. difficile, and evidence suggests that hospitalization during birth is a factor.10 Most infants are colonized with nontoxogenic strains that may stimulate a protective immune response.2,6 Infants who are colonized with toxic strains may transmit the bacteria to adults.2 Risk factors for C. difficile infection in children are similar to those for adults.6. Antibiotics. %PDF-1.5 Young C, 2010;363(16):1585]. Abujamel T, Contact precautions (e.g., private rooms with a private bathroom, putting on gloves and gowns on entry to the patient's room and removing them before exiting) should commence when C. difficile infection is suspected and should continue for at least 48 hours after resolution of the patient's diarrhea.6, In routine or endemic settings, hands should be cleaned with either soap and water or an alcohol-based product before and after contact with a patient and after removing gloves.6 During outbreaks or when direct contact with feces is likely, the use of soap and water is preferred over alcohol-based products35 based on two small studies that showed that using soap and water vs. alcohol-based products was more effective for reducing C. difficile colony-forming units.36,37 U.S. Environmental Protection Agency–registered sporicidal agents should be used to disinfect surfaces with which the patient has come into contact.6 Disposable equipment such as stethoscopes and thermometers should be used, and patients should wash their hands and shower regularly to reduce the number of spores on the skin.6 In a study of patients with C. difficile infection, showering significantly reduced positive C. difficile skin cultures vs. bed bathing.35. Fifadara N, ; 4. 15. Brown KA, Eckert C, Van Broeck J, Gerding DN, afpserv@aafp.org for copyright questions and/or permission requests. Bitton A, The nose knows not: poor predictive value of stool sample odor for detection of Clostridium difficile. Avoid testing for a Clostridioides difficile infection in the absence of diarrhea. Am Fam Physician. McDonald LC, Antimicrob Agents Chemother. Daneman N, Barbut F, If the facility does not limit C. difficile testing and evaluates patients who do not meet testing criteria, EIAs for GDH and toxins A and B can be performed initially; if results are inconclusive, NAAT alone or in combination with an EIA for toxins A and B can be ordered. Search dates: June 2018 to August 2019. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Antibiotic stewardship reduces rates of C. difficile infection. Onysko M, Dig Dis Sci. AGA utilizes … Metronidazole or vancomycin is recommended for children with an initial or first recurrence of nonsevere infection; for severe initial episodes or nonsevere recurrent episodes, oral vancomycin is preferred over metronidazole based on observational studies. et al. Clancy CJ, Buehrle D, Vu M, et al. et al. Fecal microbiota transplantation is also a reasonable option. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Thompson KA, To see the full article, log in or purchase access. Clin Infect Dis. Bartlett JG. Fidaxomicin is associated with a lower recurrence rate than oral vancomycin, but it is more expensive. Other strategies with less evidence for effective treatment of C. difficile infection include the use of probiotics and bezlotoxumab (Zinplava), the first human monoclonal antibody to C. difficile toxin B that was recently approved by the U.S. Food and Drug Administration. et al. The role of toxin A and toxin B in Clostridium difficile-associated disease: past and present perspectives. Dendukuri N, Quality of evidence takes into account study design and size of effect and dose response. The Infectious Diseases Society of America does not recommend the use of probiotics for prevention of C. difficile infection. Gerding DN, European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for. Clin Gastroenterol Hepatol. The incubation period for C. difficile is up to one week, although recent studies suggest it could be longer.6 C. difficile survives outside the colon as spores that are resistant to heat, acid, and antibiotics. Taminiau B, et al. et al. Infect Control Hosp Epidemiol. 10. Fishman EK. Clin Infect Dis. Accessed July 23, 2019. https://www.aafp.org/afp/2014/0315/p437.html, 42. VINAY C. REDDY, MD, MPH, is an assistant professor of clinical medicine in the Department of Family Medicine at the University of North Carolina. Moineddin R, Kyne L, Sethi S, New guidelines support probiotics for C. difficile prevention, but few other uses The American Gastroenterological Association recommended that probiotics be used to treat patients with Clostridioides difficile … Bitton A, Committee on Infectious Diseases; American Academy of Pediatrics. Brensinger CM, Staggered and tapered antibiotic withdrawl with administration of kefir for recurrent Clostridum difficile infection Clin Infect Dis. Cohen SH, C. difficile infection is characterized by a wide range of symptoms, from mild or moderate diarrhea to severe disease with pseudomembranous colitis, colonic ileus, toxic megacolon, sepsis, or death. Toxins A (enterotoxin) and B (cytotoxin) cause inflammation leading to mucosal injury and intestinal fluid secretion. Jury LA, 2013;131(1):196–200. Pediatrics. LaMont JT. 2016;165(9):609–616. et al. Most guidelines recommend against the use of probiotics as adjunctive therapy because of a lack of good-quality studies that show benefit. Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of Clostridium difficile. Newman KM, Crump JA, Nonsevere C. difficile infection is further stratified by initial episode and number of recurrent infections, and the treatment strategy depends on how many episodes the patient has experienced. Kim SK. This report presents FMT treatment … However, C. difficile is becoming increasingly resistant to metronidazole.25, Vancomycin, 125 mg orally 4 times per day for 10 days, Fidaxomicin (Dificid), 200 mg orally 2 times per day for 10 days, If neither agent is available: metronidazole, 500 mg orally 3 times per day for 10 days, Fidaxomicin, 200 mg orally 2 times per day for 10 days, Vancomycin, 500 mg orally or via nasogastric tube 4 times per day plus metronidazole, 500 mg intravenously every 8 hours (particularly if ileus is present), Vancomycin, 125 mg orally 4 times per day for 10 days if metronidazole was used for the initial episode, Prolonged taper and pulsed vancomycin regimen† if standard regimen was used for the initial episode, Fidaxomicin, 200 mg orally 2 times per day for 10 days if vancomycin was used for the initial episode, Prolonged taper and pulsed vancomycin regimen†, Vancomycin, 125 mg orally 4 times per day for 10 days, followed by rifaximin (Xifaxan), 400 mg orally 3 times per day for 20 days. The updated guideline … The magnitude and duration of, Brown KA, / The Guideline Recommended Treatment of Clostridioides difficile Infection (CDI) clinical quality measure is now available for use by health care organizations and clinicians as a tool to ensure they are following guideline recommended treatment … It usually gets better when the antibiotics are stopped. et al. Kasper D, <>/ExtGState<>/XObject<>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI] >>/MediaBox[ 0 0 612 792] /Contents 4 0 R/Group<>/Tabs/S/StructParents 0>> Lancet Infect Dis. Contact Fecal microbiota transplantation can be used in children with multiple recurrences in whom standard antibiotic therapy is ineffective.6, Infection control and good antibiotic stewardship are the cornerstones for reducing the incidence of C. difficile infection in health care and community settings. Clostridium difficile infection (CDI) is due to a toxin-producing bacteria that causes a more severe form of antibiotic associated diarrhea. Rodriguez C,      Print, A two-step algorithm should be used to guide diagnostic testing for Clostridioides difficile infection: enzyme immunoassay for glutamate dehydrogenase and toxins A and B, followed by nucleic acid amplification testing if initial results are indeterminate. 35. C. difficile infection should be considered in patients who are not taking laxatives and have three or more episodes of unexplained, unformed stools in 24 hours. Cadnum JL, The search included meta-analyses, randomized controlled trials, controlled trials, and reviews. Ma GK, 2 0 obj Weiss K, In 134 hospitalized patients who acquired C. difficile infection, occupying a room where a prior occupant had the infection significantly increased the risk (hazard ratio = 2.35).11 Electronic rectal thermometers and inadequately cleaned commodes and bedpans are particularly high-risk fomites.6 Shedding of C. difficile spores may continue after treatment is complete and diarrhea has resolved, resulting in asymptomatic carriers. 5. Gerding DN, et al. et al. Brensinger CM, Centers for Disease Control and Prevention. Want to use this article elsewhere? For supporting citations and to search Choosing Wisely recommendations relevant to primary care, see https://www.aafp.org/afp/recommendations/search.htm. et al. Patel S, Van Broeck J, 2012;12(4):281–289. Mody RK, 2006;145(10):758–764.... 2. 33. Loo VG, Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Willoughby RE; {L; 3YT��)����ϗ�_�����~�_�S_�NCHY��B���"����~z�]���_�x? Shift to community-onset, Centers for Disease Control and Prevention. Burden of Clostridium difficile infection in the United States. 2017;(12):CD006095. Staggered and tapered antibiotic withdrawl with administration of kefir for recurrent, Bezlotoxumab (Zinplava) for prevention of recurrent, Jury LA, Sussman DA, Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. Beardsley JR, Strength of recommendation takes into account quality of evidence; balance of benefits, harms, and burdens; the patient's values; and cost. Reprints are not available from the authors. Horton KM, Patient information: A handout on this topic is available at https://familydoctor.org/condition/clostridium-difficile-c-diff-infection. The 2017 IDSA guidelines recommend oral vancomycin or fidaxomicin (Dificid) for treatment of nonsevere initial C. difficile infection .6 Multiple randomized, placebo-controlled … Based on expert opinion, the proposed criteria for C. difficile infection severity are:6, Nonsevere infection: white blood cell count of 15,000 per mL (15.0 × 109 per L) or less and serum creatinine level less than 1.5 mg per dL (133 mmol per L), Severe infection: white blood cell count greater than 15,000 per mL or serum creatinine level of 1.5 mg per dL or greater, Fulminant colitis: hy potension, shock, ileus, or megacolon. et al. Jabbar U, Am J Med Sci. Kothari D, Alternatively, fidaxomicin can be used twice per day for 10 days. et al. 2005;71(5):921–928. Lyras D. Effectiveness of routine patient bathing to decrease the burden of spores on the skin of patients with Clostridium difficile infection. 6. Miller MA, Adjuvant tests such as fecal hemoccult and lactoferrin are not recommended for assessment of disease severity.6 In patients with signs of severe disease, radiographic imaging (e.g., plain radiography, contrast-enhanced computed tomography of the abdomen and pelvis) can be considered to look for colonic dilation, colonic wall thickening, pericolonic stranding, and ascites. The magnitude and duration of Clostridium difficile infection risk associated with antibiotic therapy: a hospital cohort study. Wu Q, PLoS One. Some may require surgery for toxic megacolon, colonic perforation, or necrotizing colitis.6.