Clostridium difficile Infection in Adults and Children

Publication Date: June 14, 2021
Last Updated: December 11, 2023

Epidemiology

Adult

To increase comparability between clinical settings, use available standardized case definitions for surveillance of healthcare facility-onset (HO) CDI, community-onset healthcare facility-associated (CO-HCFA), and community-associated (CA) CDI. (G, )
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At a minimum, conduct surveillance for healthcare facility-onset C. difficile infection (HO-CDI) in all inpatient healthcare facilities to detect elevated rates or outbreaks of CDI within the facility. ( W , L)
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Express the rate of HO-CDI as the number of cases per 10,000 patient-days. Express the CO-HCFA prevalence rate as the number of cases per 1,000 patient admissions. (G, P)
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Stratify data by patient location in order to target control measures when CDI incidence is above national and/or facility reduction goals or if an outbreak is noted. ( W , L)
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Pediatric

Use the same standardized case definitions (HO, CO-HCFA, CA) and rate expression (cases per 10,000 patient-days for HO, cases per 1,000 patient admissions for CO-HCFA) in pediatric patients as for adults. (G, )
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Conduct surveillance for HO-CDI for inpatient pediatric facilities but do not include cases <2 years of age. ( W , L)
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Consider surveillance for CA-CDI to detect trends in the community. ( W , L)
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Diagnosis

Adult

Patients with ≥3 unexplained and new onset unformed stools in 24 h are the preferred target population for testing for CDI. ( W , VL)
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Use a stool toxin test as part of a multiple step algorithm (i.e., glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no pre-agreed institutional criteria for patient stool submission (see Figure 1). ( W , L)
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Use a NAAT alone or multiple step algorithm for testing (i.e., GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are pre-agreed institutional criteria for patient stool submission (see Figure 1). ( W , L)
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Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiological studies. ( S , M)
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There are insufficient data to recommend use of biologic markers as an adjunct to diagnosis. (K, )
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Pediatric

Because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants, testing for CDI should never be routinely recommended for neonates or infants ≤12 months of age with diarrhea. ( S , M)
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C. difficile testing should not be routinely performed in children with diarrhea who are 1–2 years of age unless other infectious or noninfectious causes have been excluded. ( W , L)
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In children 2 years and older, C. difficile testing is recommended for patients with prolonged or worsening diarrhea and risk factors (such as underlying inflammatory bowel disease or immunocompromising conditions) or relevant exposures (such as contact with the healthcare system or recent antibiotics). ( W , M)
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Infection Prevention and Control

Accommodate patients with CDI in a private room with a dedicated toilet to decrease transmission to other patients. If there is a limited number of private single rooms, prioritize patients with stool incontinence for placement in private rooms. ( S , M)
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If cohorting is required, it is recommended to cohort patients infected or colonized with the same organism(s) — i.e., do not cohort patients with CDI who are discordant for other multidrug resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) or vancomycin resistant enterococcus. ( S , M)
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Healthcare personnel must use
gloves ( S , H)
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gowns ( S , M)
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on entry to a room of a patient with CDI and while caring for patients with CDI.
Patients with suspected CDI should be placed on pre-emptive contact precautions pending the C. difficile test results if test results cannot be obtained on the same day. ( S , M)
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Continue contact precautions for at least 48 hours after diarrhea has resolved. ( W , L)
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Prolong contact precautions until discharge if CDI rates remain high despite implementation of standard infection control measures against CDI. ( W , L)
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In routine or endemic settings, perform hand hygiene before and after contact with a patient with CDI and after removing gloves with either soap and water or an alcohol-based hand hygiene product. ( S , M)
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In CDI outbreaks or hyper-endemic (sustained high rates) settings, perform hand hygiene with soap and water preferentially instead of alcohol-based hand hygiene products before and after caring for a patient with CDI, given the increased efficacy of spore removal with soap and water. ( W , L)
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Handwashing with soap and water is preferred if there is direct contact with feces or an area where fecal contamination is likely, e.g., the perineal region. (G, )
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Encourage patients to wash hands and shower to reduce the burden of spores on the skin. (G, )
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Use disposable patient equipment when possible and ensure that reusable equipment is thoroughly cleaned and disinfected, preferentially with a sporicidal disinfectant that is equipment compatible. ( S , M)
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Terminal room cleaning with a sporicidal agent should be considered in conjunction with other measures to prevent CDI during endemic high rates or outbreaks or if there is evidence of repeated cases of CDI in the same room. ( W , L)
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Incorporate measures of cleaning effectiveness to ensure quality of environmental cleaning. (G, )
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There are limited data at this time to recommend use of automated, terminal disinfection using a sporicidal method for CDI prevention. (K, )
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Daily cleaning with a sporicidal agent should be considered in conjunction with other measures to prevent CDI during outbreaks or in hyperendemic (sustained high rates) settings, or if there is evidence of repeated cases of CDI in the same room. ( W , L)
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There are insufficient data to recommend screening for asymptomatic carriage and placing asymptomatic carriers on contact precautions. (K, )
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Minimize the frequency and duration of high-risk antibiotic therapy and the number of antibiotic agents prescribed, to reduce CDI risk. ( S , M)
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Implement an antibiotic stewardship program. (G, )
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Antibiotics to be targeted should be based on the local epidemiology and the C. difficile strains present. Restriction of fluoroquinolones, clindamycin and cephalosporins (except for surgical antibiotic prophylaxis) should be considered. ( S , M)
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Although there is an epidemiologic association between proton pump inhibitors (PPIs) use and CDI, and unnecessary PPIs should always be discontinued, there is insufficient evidence for discontinuation of PPIs as a measure for preventing CDI. (K, )
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There are insufficient data at this time to recommend administration of probiotics for primary prevention of CDI outside of clinical trials. (K, )
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Treatment

Adult

Discontinue therapy with the inciting antibiotic agent(s) as soon as possible, since this may influence the risk of CDI recurrence. ( S , M)
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Antibiotic therapy for CDI should be started empirically for situations where a substantial delay in laboratory confirmation is expected, or for fulminant CDI*. ( W , L)
* Fulminant CDI, previously referred to as severe, complicated CDI, may be characterized by hypotension or shock, ileus, or megacolon.
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For patients with an initial CDI episode, we suggest using fidaxomicin rather than a standard course of vancomycin. (C, M)
Comment: This recommendation places a high value in the beneficial effects and safety of fidaxomicin, but its implementation depends upon available resources. Vancomycin remains an acceptable alternative.
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In settings where access to vancomycin or fidaxomicin is limited,
we suggest using metronidazole for an initial episode of non-severe CDI* only. The suggested dosage is metronidazole 500 mg orally 3 times per day for 10 days. ( W , H)
* See Table 3 for definition of CDI severity.
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Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity. ( S , M)
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For fulminant CDI,*
Vancomycin administered orally is the regimen of choice. ( S , M)
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If ileus is present vancomycin can also be administered per rectum. ( W , L)
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The vancomycin dosage is 500 mg orally 4 times per day and 500 mg in approximately 100 mL normal saline per rectum every 6 hours as a retention enema. Intravenously administered metronidazole should be administered together with oral or rectal vancomycin particularly if ileus is present. ( S , M)
Notes: The metronidazole dosage is 500 mg intravenously every 8 hours.
* Fulminant CDI is described above.
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If surgical management is necessary for severely ill patients,
Perform subtotal colectomy with preservation of the rectum. ( S , M)
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Diverting loop ileostomy with colonic lavage followed by antegrade vancomycin flushes is an alternative approach that may lead to improved outcomes. ( W , L)
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In patients with recurrent CDI episodes, we suggest fidaxomicin (standard or extended-pulsed regimen) rather than a standard course of vancomycin. (C, L)
Comment: Vancomycin in a tapered and pulsed regimen or vancomycin as a standard course are acceptable alternatives for a first CDI recurrence. 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.
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For patients with a recurrent CDI episode within the last six months, we suggest using bezlotoxumab as a co-intervention along with standard-of-care (SOC) antibiotics rather than SOC antibiotics alone. (C, VL)
Comment: This recommendation places a high value on potential clinical benefits, but implementation is often limited by feasibility considerations. In settings where logistics is not an issue, patients with a primary CDI episode and other risk factors for CDI recurrence (such as age ≥65 years, immunocompromised host [per history or use of immunosuppressive therapy], and severe CDI on presentation) may particularly benefit from receiving bezlotoxumab. Data on the use of bezlotoxumab when fidaxomicin is used as the SOC antibiotic are limited. The Food and Drug Administration warns that “in patients with a history of congestive heart failure (CHF), bezlotoxumab should be reserved for use when the benefit outweighs the risk.”
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Fecal microbiota transplantation (FMT) is recommended for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments. ( S , M)
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There are insufficient data at this time to recommend extending the length of anti-C. difficile treatment beyond the recommended treatment course or re-starting an anti-C. difficile agent empirically for patients who require continued antibiotic therapy directed against the underlying infection or who require re-treatment with antibiotics shortly after completion of CDI treatment, respectively. (K, )
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Pediatric

Either metronidazole or vancomycin is recommended for the treatment of children with an initial episode or first recurrence of non-severe CDI (see Table 4 for dosing). ( W , L)
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For children with an initial episode of severe CDI, oral vancomycin is recommended over metronidazole. ( S , M)
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For children with a second or greater episode of recurrent CDI, oral vancomycin is recommended over metronidazole. ( W , L)
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Consider fecal microbiota transplantation (FMT) for pediatric patients with multiple recurrences of CDI following standard antibiotic treatments. ( W , VL)
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Table 4. Recommendations for the Treatment of C. difficile Infection (CDI) in Children

Initial episode, non-severe:
Recommended Treatment: Metronidazole × 10 days (PO)
Pediatric Dose: 7.5 mg/kg/dose tid or qid
Maximum Dose: 500 mg tid or qid ( W , L)
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Recommended Treatment: Vancomycin x 10 days (PO)
Pediatric Dose: 10 mg/kg/dose qid
Maximum Dose: 125 mg qid ( W , L)
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Initial episode, severe/fulminant:
Recommended Treatment: Vancomycin × 10 days (PO or PR), (WITH OR WITHOUT Metronidazole)
Pediatric Dose: 10 mg/kg/dose qid
Maximum Dose: 500 mg qid ( S , M)
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Recommended Treatment: Metronidazole × 10 days (IV)a
Pediatric Dose: 10 mg/kg/dose tid
Maximum Dose: 500 mg tid ( W , L)
a In cases of severe or fulminant CDI associated with critical illness, consider addition of intravenous metronidazole to oral vancomycin.
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First recurrence, non-severe:
Recommended Treatment: Metronidazole × 10 days (PO)
Pediatric Dose: 7.5 mg/kg/dose tid or qid
Maximum Dose: 500 mg tid or qid ( W , L)
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Recommended Treatment: Vancomycin x 10 days (PO)
Pediatric Dose: 10 mg/kg/dose qid
Maximum Dose: 125 mg qid (, )
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Second or subsequent recurrence:
Recommended Treatment: Vancomycin in a tapered and pulsed regimenb
Pediatric Dose: 10 mg/kg/dose qid
Maximum Dose: 125 mg qid ( W , L)
b Tapered and pulsed regimen as described in Table 2: Vancomycin 10 mg/kg with max of 125 mg qid for 10–14 days, then 10 mg/kg with max of 125 mg bid for a week, then 10 mg/kg with max of 125 mg qd for a week, and then 10 mg/kg with max of 125 mg q2–3d for 2–8 weeks.
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Recommended Treatment: Vancomycin for 10 days followed by rifaximinc for 20 days
Pediatric Dose: Vancomycin: 10 mg/kg/dose qid; Rifaximin: no pediatric dosing
Maximum Dose: Vancomycin:500 mg qid; Rifaximin: 400 mg tid ( W , L)
c No pediatric dosing for rifaximin. Not approved by the US FDA for use in children <12 years of age.
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Recommended Treatment: Fecal microbiota transplantation ( W , VL)
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Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Clostridium difficile Infection in Adults and Children

Authoring Organizations

Infectious Diseases Society of America

Society for Healthcare Epidemiology of America

Endorsing Organizations

American Society of Health-System Pharmacists

Pediatric Infectious Diseases Society

Society of Infectious Diseases Pharmacists

Publication Month/Year

June 14, 2021

Last Updated Month/Year

November 7, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Target Patient Population

Adults with Clostridioides difficile infection (CDI)

PICO Questions

  1. In patients with an initial Clostridioides difficile infection episode, should fidaxomicin be used rather than vancomycin?

  2. In patients with recurrent CDI episode(s), should fidaxomicin be used rather than vancomycin?

  3. In patients with a CDI episode, should bezlotoxumab be used as a co-intervention along with standard-of-care antibiotics rather than standard-of-care antibiotics alone?

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Ambulatory, Hospital

Intended Users

Epidemiology infection prevention, nurse, nurse practitioner, health systems pharmacist, physician, physician assistant

Scope

Diagnosis, Assessment and screening, Treatment, Management, Prevention

Diseases/Conditions (MeSH)

D016360 - Clostridium difficile, D003013 - Clostridium, D003015 - Clostridium Infections

Keywords

diarrhea, Clostridium difficile, C diff, Clostridioides difficile, CDI, CDAD, Cdiff

Source Citation

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. Clin Infect Dis, 2021; 73(5), e1029-e1044. doi: 10.1093/cid/ciab549

McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridioides difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66(7): e1-e48.

Methodology

Number of Source Documents
390
Literature Search Start Date
December 4, 2012
Literature Search End Date
December 31, 2016