Strategies to Prevent Clostridioides difficile Infections in Acute-Care Hospitals

Publication Date: April 12, 2023
Last Updated: January 19, 2024

Summary of Recommendations

Essential Practices

Encourage appropriate use of antimicrobials through implementation of an antimicrobial stewardship program
  • Ensure appropriate use of antimicrobials for CDI treatment.
  • Ensure appropriate use of non–CDI-treatment antimicrobials.
Implement diagnostic stewardship practices for ensuring appropriate use and interpretation of C. difficile testing.
  • Hospital infection prevention and control programs should work with their clinical microbiology laboratory to develop pre-agreed criteria for C. difficile testing, particularly if NAATs are used either as a standalone test or part of a multi-step testing algorithm.
  • At minimum, C. difficile testing should be avoided in patients without clinically significant diarrhea, in those who have been tested in the prior 7 days, and in children aged <1 year.
  • Ordering providers and bedside nurses should receive education about appropriate use and interpretation of C. difficile testing.
  • If feasible, the electronic medical record system should be leveraged to provide computerized provider order entry support and/or monitoring for clinical testing criteria.
Use contact precautions for infected patients, single-patient room preferred, including
hand hygiene (Low)
gloves (Moderate)
single-patient room (Low)
  • Perform hand hygiene based on CDC or WHO guidelines before and after entering the room (ie, immediately before donning and after removing personal protective equipment).
  • Place patients with CDI on contact precautions to help reduce patient-to-patient spread of the organism.
  • Cohorting of patients with CDI is acceptable when single private rooms are not available.
  • Ensure that adequate supplies for contact precautions are readily available.
  • Follow appropriate criteria for discontinuing contact precautions.
Adequately clean and disinfect equipment and the environment of patients with CDI.
  • C. difficile spores contaminate the environment in which patients are housed and the equipment used to care for them.
  • Contaminated surfaces and equipment are potential reservoirs for transmission of C. difficile.
  • Develop and implement protocols for disinfection of equipment and the environment.
  • Dedicate noncritical patient care items, such as blood pressure cuffs, stethoscopes, and thermometers, to a single patient with C. difficile.
Assess the adequacy of room cleaning.
  • Work with the environmental services team to establish a process for assessing adequacy of room cleaning at a frequency that is feasible for the team.
  • The process should focus on reviewing and improving cleaning/disinfection techniques. Important issues to address include proper dilution of cleaning/disinfection products, adequacy of cleaning/disinfection technique, cleaning “high-touch” surfaces, frequency of changing rags/mop water, and moving from “clean” areas to “dirty” areas.
  • Consider environmental decontamination with an EPA-approved sporicidal agent if room cleaning/disinfection is deemed to be adequate but there is ongoing C. difficile transmission.
Implement a laboratory-based alert system to provide immediate notification to infection preventionists and clinical personnel about newly diagnosed patients with CDI.
  • To place patients with CDI on contact precautions in a timely manner, it is important that an alert system be developed between the laboratory and both infection preventionists and the clinical personnel caring for the patient.
  • This information can be transmitted using a variety of methods. Options that push notifications to those HCP who need to act on the information immediately are preferred, such as phone call and pager alerts or automated secure electronic alerts. The alert system should not rely solely on passive communications that may delay receipt of results, such as faxes or emails to infrequently monitored inboxes.
  • Alert patient care areas of positive test results immediately so that these patients can be placed on contact precautions as soon as possible.
  • When a patient has CDI (or another current or prior infection requiring isolation), communicate the CDI/isolation status when transferring the patient to another healthcare facility so appropriate precautions can be implemented at the accepting facility.
Conduct CDI surveillance and analyze and report CDI data.
  • At a minimum, calculate healthcare facility–onset CDI rates at the organizational level and consider specifically calculating CDI rates by unit or ward (Table 3).
  • Provide CDI rates and CDI prevention process measures to key stakeholders including senior leadership, physicians, nursing staff, and other clinicians.
  • Provide the process and outcome measures to appropriate hospital staff and administrators on a regular basis as outlined in Section 5: Performance measures.
Educate HCP, environmental service personnel, and hospital administration about CDI. Include risk factors, routes of transmission, local CDI epidemiology, patient outcomes, and treatment and prevention measures. (Low)
Educate patients and their families about CDI as appropriate. Although often not considered part of a program to reduce transmission of CDI and/or multidrug-resistant organisms, proper education may help to alleviate patient and family fears regarding being placed on contact precautions. Include information about anticipated questions: general information about CDI, colonization versus infection, the hospital’s CDI prevention program, the components of and rationale for contact precautions, the risk of transmission to family and visitors while in the hospital and after discharge, and importance of hand hygiene by staff, patients, and visitors. (Low)
Measure compliance with CDC or WHO hand hygiene and contact precautions recommendations.
  • Patient-to-patient transmission of C. difficile is thought to occur primarily through transient contamination of the hands of HCP with spores.
  • Glove use when caring for patients with CDI or touching surfaces in their rooms has been shown to be effective at preventing the transmission of C. difficile.
  • Hand hygiene practices in compliance with CDC or WHO guidelines may be important to C. difficile control and prevention.

Additional Approaches

Intensify the assessment of compliance with process measures.
  • Contact precautions: gowns and gloves should be worn by all HCP who enter the rooms of patients on contact precautions.
  • Hand hygiene: hand hygiene should be performed at least on entry and exit from patient rooms. When hand washing is performed, determine whether proper technique is being used. If hand hygiene compliance or technique are not adequate, conduct interventions to improve hand hygiene compliance and technique.
  • Assess opportunities for improved antibiotic and/or diagnostic test utilization with improved compliance with and/or using additional antibiotic or diagnostic stewardship (see Section 4: Essential practices, parts 1 and 2).
As the preferred method, perform hand hygiene with soap and water following care of or interacting with the healthcare environment of a patient with CDI.
  • When considering a CDI-specific hand hygiene measure, the priority should be to ensure adherence to donning gloves and proper technique when doffing to minimize the risk for self-contamination.
  • Ideally, after removing gloves, hand hygiene is performed before exiting the patient room when feasible.
  • Ensure proper hand hygiene technique when using soap and water.
  • Be aware that hand hygiene adherence may decrease when soap and water is the preferred method.
Place patients with diarrhea on contact precautions while C. difficile testing is pending.
  • Place patients with new-onset, unexplained diarrhea on contact precautions when diarrhea is recognized. Employ measures (see Section 4: Essential practices, part 3), particularly use of gowns/gloves and disinfection of shared medical equipment. Contact precautions should be initiated as soon as diarrhea symptoms are recognized because this is the period of greatest C. difficile shedding and contamination.
  • Availability of private rooms or ability to cohort patients in nonprivate rooms before a CDI diagnosis may be a challenge for some hospitals. In these settings, the decision to place a patient on contact precautions in a private or cohort room while testing is pending can be based on several factors, including likelihood that patient will transmit C. difficile, turnaround time of CDI test results, and impact of contact precautions on hospital bed management.
  • If C. difficile testing is negative, and another infectious etiology that requires contact precautions is not suspected, contact precautions can be discontinued based on test type and clinical suspicion for CDI.
Prolong the duration of contact precautions after the patient becomes asymptomatic until hospital discharge.
  • CDC currently recommends contact precautions for patients with CDI for at least 48 hours after diarrhea resolves. However, some hospitals may choose to extend contact precautions for the duration of hospitalization even if symptoms have resolved.
  • Facilities must balance potential reduction in C. difficile transmission with individual patient risk of isolation related to contact precautions, which may include falls and socioemotional stress that can lead to symptoms such as behavior changes, anxiety, depression, and anger.
Use an EPA-approved sporicidal disinfectant, such as diluted (1:10) sodium hypochlorite, for environmental cleaning/disinfection. Implement a system to coordinate with environmental services if it is determined that sodium hypochlorite is needed for environmental disinfection.
  • Sporicidal disinfectants registered with the EPA, including sodium hypochlorite, can be found in the EPA List K.
  • Data have not been consistent regarding the ability of sporicidal disinfectants, including diluted sodium hypochlorite, to control CDI through environmental decontamination.
  • When an EPA-approved sporicidal disinfectant is instituted for environmental decontamination, it is necessary to coordinate activities with environmental services.
  • When diluted (1:10) sodium hypochlorite is used, it is important to address several issues including measures to avoid toxicity to patients and staff, removal of organic matter from surfaces before use, and using freshly diluted or appropriately stored diluted sodium hypochlorite.
  • When a sporicidal method will be used only in rooms of patients with CDI, a system will need to be created to identify these patients to environmental service staff.

Unresolved Issues

  1. Identification of asymptomatic carriers of toxigenic C. difficile using rectal or perirectal swabs and NAAT testing and placing those who are positive on contact precautions.
  2. Implementation of touchless disinfection technologies.
  3. Use of probiotics as primary prophylaxis.
  4. CDI antibiotic prophylaxis for certain very high-risk patients who are receiving systemic antibiotics.
  5. Use of gowns and gloves by family members and other visitors.
  6. Use of admission-based alert systems that notify infection preventionists and clinical personnel about readmitted or transferred patients with a history of CDI.
  7. Ongoing assessment of CDI knowledge and intensified CDI education among HCP.
  8. Restriction of gastric acid suppressants.

Rationale and statements of concern

Epidemiology of Clostridioides difficile infection (CDI)

  1. C. difficile is the most common pathogen causing HAIs in the United States (US).
  2. In the US, C. difficile has been classified by the CDC as one of the most urgent antibiotic-resistant public health threats, one that requires “urgent and aggressive action." This classification is because of the profound morbidity, mortality, and excess healthcare expenditures associated with CDI.
  3. Over the past 20 years, CDI increased among all age groups, including children, but it remains disproportionately higher in the older adult population. Women and individuals identifying as white race also experience higher frequency of CDI. The proportion of US hospital discharges in which a patient received the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis code for CDI more than doubled between 2000 and 2009.
  4. More recently, improvements in those previously described trends were observed. US CDI surveillance performed by the CDC Emerging Infections Program noted that since 2014, CDI incidence has leveled off and is perhaps beginning to decrease. However, this trend was marked by a decrease in healthcare-associated (HA) CDI concomitant with an increase in community-associated (CA) CDI. CDI with onset outside the hospital now accounts for >50% of US CDI cases. CDI present on admission to the hospital may increase the risk of CDI for other hospitalized patients.Notably, laboratory-identified healthcare-associated CDI decreased during the first year (ie, 2020) of the coronavirus disease 2019 (COVID-19) pandemic.
  5. CDI incidence increased in the early 2000s concomitant with observations of increased CDI severity. Increases in incidence and severity of CDI were associated with the 027/BI/NAP1 strain of C. difficile. However, 027/BI/NAP1 cases has declined significantly in the US8, Canada, and Europe.In the US in 2017, the prevalence of the 027/BI/NAP1 strain was 15% of HA-CDI and 6% of CA-CDI cases. Currently, 027/BI/NAP1 is no longer the predominant US strain. Ribotypes 106, 002, and 014/020 have increased in prevalence over the last several years.

Burden of outcomes associated with CDI

  1. CDI is associated with increased length of hospital stay, costs, morbidity, and mortality in adult and pediatric patients.
  2. C. difficile causes >450,000 infections in the US each year, including >225,000 cases in hospitalized patients.
  3. CDI increases hospital length of stay by 2.8–5.5 days.
  4. Approximately 10%–30% of patients experience at least 1 CDI recurrence after an initial episode, and the risk of recurrence increases following each successive recurrence.
  5. The attributable mortality of CDI is estimated to be 4.5%–5.7% and 6.9%–16.7% during endemic and epidemic periods, respectively. CDI is associated with 12,000–30,000 US deaths each year.
  6. Colectomy rates following CDI in hospitalized patients are 0.3%–1.3% and 1.8%–6.2% during endemic and epidemic periods, respectively.
  7. Attributable costs of inpatient CDI in 2008 dollars were estimated to be $3,006–$15,397 per episode in adults; more recent US estimates indicate that average CDI-attributable costs exceed $21,000. Attributable costs are slightly less in children. US hospital costs for CDI management are estimated at $1.0 billion–$4.9 billion per year.
  8. Patients with CDI are nearly twice as likely to be discharged to a long-term care facility than propensity score–matched controls.

Risk factors for CDI

  1. Antibiotic exposure is the most important modifiable risk factor for CDI. Virtually every antibiotic has been associated with CDI, even following short antibiotic courses. Antibiotic classes that confer the highest risk of CDI include third- and fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin.
  2. Advanced age and duration of hospitalization are also important CDI risk factors, and these may be proxy measures associated with severity of illness, comorbidities, and antibiotic exposure.
  3. Gastric acid suppression, particularly use of proton pump inhibitors, has been recognized as a risk factor for CDI. The association between CDI and H2-receptor blockers is less established. It remains unclear whether there is an independent association or gastric acid suppression is a proxy for other CDI risk factors, and restriction of gastric acid suppression is not yet established as an effective CDI prevention measure.
  4. Other comorbidities that increase CDI risk include cancer chemotherapy, gastrointestinal surgery, enteral feeding tubes, inflammatory bowel disease, and solid organ transplantation.

Healthcare facility transmission and role of asymptomatic colonization

  1. C. difficile exposure, and subsequent colonization, are preceding events that are essential to developing CDI. Thus, prevention of exposure and colonization are targets for CDI prevention.
  2. C. difficile transmission in healthcare facilities likely occurs via contamination of healthcare personnel (HCP) hands, the care environment, or medical equipment by C. difficile spores.
  3. Prevalence of asymptomatic colonization with C. difficile during hospitalization is as high as 20%–25% of adults and children in some centers. The prevalence of asymptomatic colonization with C. difficile at the time of hospital admission is ∼8%.
  4. C. difficile transmission can originate both from patients with CDI and those with asymptomatic colonization. Studies demonstrating that symptomatic patients contribute to only a minority of HA-CDI cases suggest that other reservoirs for transmission may be underrecognized, including patients with asymptomatic colonization.

Background on detection of CDI

Surveillance definitions for CDI

Various surveillance definitions are used for healthcare-associated CDI, and standardization in CDI surveillance definitions is needed. The following information focuses on the definitions for CDI surveillance in the United States and Europe
  1. A clinical CDI case is defined as a case of clinically significant diarrhea or toxic megacolon without other known etiology that meets 1 or more of the following criteria: (1) the stool sample yields a positive result for a laboratory assay for C. difficile toxin A and/or B, or a toxin-producing C. difficile organism is detected in the stool sample by culture or other means; (2) pseudomembranous colitis is seen on endoscopic examination or surgery; and/or (3) pseudomembranous colitis is seen on histopathological examination. Large-scale surveillance efforts may rely solely on laboratory evidence of CDI (ie, LabID events) (see Section 2: Surveillance definitions for CDI, part 1e) because surveillance for clinical history may not be feasible or reliable across all healthcare facilities.
  2. The definition of clinically significant diarrhea has not been validated either for stool quality or quantity. In terms of stool consistency, diarrheal stool may be operationally defined as stool that is unformed and adheres to shape of its container. The Bristol Stool Scale may assist in scoring stool quality (ie, unformed stools defined as Bristol score 5–7). In terms of stool quantity, diarrhea is defined at least 3 or >3 diarrheal bowel movements within 24 hours.
  3. HCP should document frequency and consistency of stools in the medical record.
  4. Recent outbreaks of severe CDI indicate that it is not always possible to wait 24–48 hours before determining whether a patient has clinically significant diarrhea; therefore, diarrhea plus abdominal cramping has also been used to satisfy criteria for clinically significant diarrhea. Conversely, it is normal for some patients to have 3 or more bowel movements per day. However, these bowel movements are usually formed. Therefore, it is not possible to provide strict criteria for clinically significant diarrhea that can be applied to all patients. In general, clinically significant diarrhea in the context of CDI should consist of a sustained change in bowel movement consistency and/or frequency with or without abdominal cramping in a patient without other identified causes.
  5. Several CDI definitions have been proposed, and the most commonly used surveillance definitions are listed in Table 3. Healthcare facilities should track at least healthcare facility-onset CDI (Table 3).
    1. Hospitals in the US typically apply the National Healthcare Safety Network (NHSN) LabID event definitions to CDI,as reporting CDI incidence through NHSN is required for certain Centers for Medicare & Medicaid Services (CMS) payment programs for acute-care facilities. This reporting focuses on positive laboratory tests in relation to hospital admission and does not consider the presence or timing of onset of symptoms. Healthcare facility–onset CDI is defined as having a positive nucleic acid amplification test (NAAT) or toxin (based on the result of the last test performed if a multistep algorithm is done) ≥4 days after healthcare facility admission, with the day of admission counted as day 1. An event may be identified as ‘recurrent’ when there is a previous event at the same facility in the previous 56 days. If the event is the first for that patient at the facility or day 57 or longer from previous event, the event is identified as an incident of CDI. An equation is used to determine the predicted number of hospital-onset CDI cases for a hospital based on the hospital characteristics, type of C. difficile testing done, and number of people admitted with community-onset CDI. The standardized infection ratio (SIR) is then calculated by dividing the number of observed healthcare facility–onset CDI cases by the number of predicted healthcare facility–onset CDI cases.
    2. Because the result of the last test performed in a multistep testing algorithm dictates whether a case is reportable to the NHSN, the pattern of results of tests performed in a different order can significantly impact the SIR. For example, a glutamate dehydrogenase (GDH)–positive, toxin enzyme immunoassay (EIA)–negative result that is followed by a positive NAAT is considered reportable to NHSN as a CDI case, but a NAAT-positive result followed by a negative-toxin EIA is not reportable to the NHSN as a CDI case. This discordance represents a weakness in the surveillance definition because clinical management is not dictated solely by the result of the last test performed. However, data from the CDC (not yet published) suggest that >75% of patients are treated for CDI despite having a negative toxin EIA following a positive NAAT even though data suggest that treatment may not be necessary. Failing to report this volume of clinical CDI cases based on order of test performance biases SIR measurements and interfacility comparisons.
    3. The NHSN is updating the healthcare facility-onset CDI surveillance definition to incorporate antibiotic treatment in addition to test results (ie, healthcare facility-onset, treated CDI [HT-CDI]).
      1. Data have demonstrated the existence of patients with a positive test for C. difficile who do not meet the current NHSN definition for healthcare facility-onset CDI but who ultimately received treatment for CDI, suggesting that they were determined to have clinically significant CDI and should likely be considered a CDI case for surveillance purposes.
      2. The updated definition is still undergoing validation, but it will involve a combination of any positive test for C. difficile plus initiation of antibiotics specifically for treatment of CDI.
        1. For the most likely proposed definition, a case of HT-CDI will be defined as any positive test for C. difficile on or after hospital day 4 from admission, and in whom ≥5 days of CDI treatment were given, and treatment was started within 2 calendar days of the positive C. difficile test. If a patient is discharged or transferred before receiving 5 days of treatment, any treatment will count.
        2. Data submitted to meet this metric are expected to be available in 2023.
        3. Until the HT-CDI definition and corresponding SIR adjustment can be validated, the current healthcare facility-onset CDI definition will continue to be used as the outcome measure for CDI surveillance and SIR reporting for the purposes of CMS payment programs.
  6. Surveillance for CDI is limited by variation in patient selection for testing, lower sensitivity of toxin EIA, lower specificity of NAAT, and prolonged turnaround time for the cell-culture cytotoxicity assay as well as stool culture for toxigenic C. difficile.Reference Dubberke, Han and Bobo53,Reference Longtin, Trottier and Brochu57,Reference Planche, Davies and Coen58 Lack of culture-based methods for routine diagnosis also limits the availability of strains for molecular typing, but at least 1 commercially available NAAT for C. difficile will provide a presumptive identification of the BI/NAP1/027 strain.

Table 3. Commonly Used Clostridioides difficile Infection (CDI) Surveillance Definitions

Having trouble viewing table?
Case Type Definition
Healthcare facility–onset CDI (HO-CDI) CDI symptom onset ≥4 days after admission to an HCF, with day of admission being day 1.
Healthcare facility–onset, treated CDI (HT-CDI) The proposed definition is currently being evaluated CDI symptom onset ≥4 days after admission to a healthcare facility (HCF), with day of admission being day 1, and ≥5 days of CDI treatment started within 2 calendar days of the positive C. difficile test; if a patient is discharged or transferred before receiving 5 days of treatment, any treatment will count.
Community-onset, healthcare facility-associated CDI (CO-HCFA-CDI) CDI symptom onset in the community or <4 days from admission (day of admission being day 1), provided that symptom onset was <4 weeks after the last discharge from an HCF, according to NHSN definitions.
Indeterminate onset CDI CDI case patient who does not fit any of the above criteria for an exposure setting, eg, CDI symptom onset in the community or <4 days from admission (day of admission being day 1) provided that symptom onset was >4 weeks but <12 weeks after the last discharge from an HCF.
Community-associated CDI (CA-CDI) CDI symptom onset in the community or < 4 days from admission (day of admission being day 1), provided that symptom onset was >12 weeks after the last discharge from an HCF.
Healthcare-associated CDI (HA-CDI) Includes cases of HO-CDI, CO-HCFACDI, and indeterminate per CDC Emerging Infections Program definitions.
Community-onset CDI (CO-CDI) Includes Includes both CA-CDI and indeterminate CDI (distinct from COHCFA- CDI) per NHSN definitions.
Unknown Exposure setting cannot be determined because of lack of available data.
Recurrent CDI A CDI episode that occurs 8 weeks (56 days) or less after the onset of a previous CDI episode, provided that CDI symptoms from the earlier episode resolved.

Table 4. Clostridioides difficile Infection (CDI) Prevention Process and Outcome Measures

Having trouble viewing table?
Process Measures
Compliance with hand hygiene guidelines: If hand hygiene with soap and water is the preferred method of hand hygiene when caring for patients with CDI, also assess proper hand washing technique with the same formula. (No. of observed proper hand hygiene episodes performed by HCP ÷ total no. of observed opportunities for hand hygiene) × 100 = % compliance with hand hygiene compliance
Compliance with contact precautions (No. of observed patient care episodes in which contact precautions are appropriately implemented ÷ the no. of observed patient care episodes in which contact precautions are indicated) × 100 = % compliance with contact precautions
Compliance with environmental cleaning and disinfection One specific measure of compliance for use in all hospitals cannot be recommended. However, many hospitals use checklists, environmental rounds, fluorescent markers, and/or ATP bioluminescence to assess the cleaning and disinfection process and cleanliness of equipment and the environment
Outcomes Measures
• Calculate CDI rates
• See Table 3 for case definitions
(No. of CDI cases in the population being monitored ÷ total number of patient days in the population being monitored) × 10,000 = No. of CDI cases per 10,000 patient days

Surveillance methods for CDI

  1. Conducting CDI surveillance to determine CDI rates provides a measure to determine the burden of CDI at a healthcare facility. These data are also utilized to assess the efficacy of interventions to prevent CDI. When reported back to HCP and hospital administrators, CDI rates can be applied as a tool to improve adherence to CDI preventive measures.
    1. When conducting CDI surveillance, healthcare facilities can use traditional infection surveillance reporting or laboratory-based reporting.
      1. Traditional reporting involves chart review to determine the date of symptom onset and whether the patient meets the surveillance definition for CDI. Potential cases are typically identified by a stool laboratory test positive for toxigenic C. difficile and/or its toxins.
      2. Laboratory-based reporting also utilizes positive tests to identify cases, but chart review is not performed. Rather, it is assumed that all positive tests represent patients with CDI, and the date of stool collection is used as a proxy for date of symptom onset.
    2. Comparisons between the methods of surveillance have been performed, and the 2 methods typically have good concordance in correctly categorizing CDI cases into the proper surveillance definition.
      1. Although there are concerns that laboratory-based surveillance is less accurate and more likely to incorrectly classify community-onset CDI cases as healthcare-facility onset, excellent sensitivity and specificity of an electronic surveillance algorithm has been demonstrated. Even with the potential for some misclassification, the time saved by laboratory-based surveillance is often determined to outweigh the risk. In addition, identification of misclassification is an opportunity for improvement.
      2. Rapid identification and implementation of contact precautions for patients with CDI is paramount to prevent C. difficile transmission. Patients with community-onset CDI who are not identified until it is classified as healthcare facility-onset CDI represent delays in CDI diagnosis and initiation of contact precautions.
  2. Surveillance can be performed on specific wards or units and/or an entire healthcare facility level.
  3. Infection prevention and control programs should have a system in place for reviewing results of positive C. difficile tests in patients included in their CDI surveillance plan to ensure accurate and complete case ascertainment. The healthcare facility-onset CDI rate can be expressed as the number of CDI case patients per 10,000 patient days. The calculation of this rate is (number of case patients ÷ the number of inpatient days per reporting period) × 10,000 = rate per 10,000 inpatient days.
  4. Outbreaks and hyperendemic rates can occur at the ward level.
    1. An outbreak can be defined as an increase in CDI in time and/or space believed to be greater than that expected by chance alone for a given healthcare facility or ward.
    2. A hyperendemic rate can be defined as a persistently elevated CDI rate compared to past rates or compared to other similar healthcare facilities and/or wards.

Identification of patients with CDI and appropriate test utilization

  1. Background:
    1. Positive results of diarrheal stool tests for toxigenic C. difficile (ie, NAAT) or its toxins (ie, EIA) are the most common methods to identify patients with CDI. A minority of patients are diagnosed by visualizing pseudomembranes at endoscopy and/or by histopathology without stool testing. NAATs, which detect toxigenic C. difficile, are extraordinarily sensitive but do not reliably differentiate C. difficile colonization and infection. Toxin EIAs, which detect C. difficile toxins, are less sensitive than NAATs but have greater clinical predictive value for CDI.
    2. These distinctions between test types are important because C. difficile colonization can occur in up to 20%–25% of children and adults over the course of their hospitalization and is more likely to occur with prolonged and/or repeated hospitalizations. Thus, the specific test used and the scenarios during which patients are tested will affect the clinical predictive value of the test and the likelihood of misdiagnosis of C. difficile colonization as CDI. Several diagnostic stewardship strategies are effective for reducing misdiagnosis of CDI in individuals who are colonized with C. difficile (Section 2: Identification of patients and appropriate test utilization, part 1b).
    3. The impact of CDI misdiagnosis: Frequent misdiagnosis of C. difficile colonization as CDI falsely increases institutional CDI rates, which may be publicly reported. Misdiagnosis impairs reliable interfacility comparisons of CDI rates and increases inappropriate use of antibiotics for CDI, which may result in increased healthcare costs, risk of antibiotic-related adverse events, antimicrobial resistance, and prolonged use of contact precautions (ie, isolation).
  2. Potential strategies for improving test utilization:
    1. Institutions should establish criteria for CDI test collection, processing, and test interpretation. This is important irrespective of test type but is particularly important when NAATs are used either as a standalone test or multi-step testing algorithm. If a multistep algorithm is used, hospitals should develop clinical practice guidance for the treatment of patients who are toxin EIA positive versus those positive only by NAAT. HCP should receive education about the availability and use of that clinical practice guideline.
    2. Testing criteria may include several factors, including the presence of diarrhea, recent CDI testing history, and the presence of factors that increase likelihood of other non-CDI diarrheal etiologies. Evidence-based testing strategies include the following:
      1. When diagnosing CDI, only test patients with clinically significant diarrhea for C. difficile or its toxins. Clinically significant diarrhea is defined as 3 or more unexplained and new-onset, unformed stools in the 24-hour period prior to testing. Unexplained diarrhea implies lack of an alternative explanation, but HCP should be aware that CDI and other potential alternative explanations may not be mutually exclusive (eg, patients on laxatives or who recently started enteral feeds can also have CDI). Effort should be taken to discern diarrhea chronology and associated symptoms to discern CDI from alternative explanations to guide testing decisions.
        1. Testing of those without diarrhea should not be part of routine clinical practice (see Section 4: Essential practices, part 2).
        2. For patients without clinically significant diarrhea, testing should only be pursued if other CDI signs or symptoms are present that may reduce stool output, such as ileus or toxic megacolon.
      2. Prior to testing for C. difficile in patients with new-onset diarrhea, thoughtful consideration should be given to other potential infectious or noninfectious diarrhea etiologies. This includes current use of medications that result in diarrhea, such as laxatives. In some circumstances, it may be reasonable to hold laxatives to observe for resolution of diarrhea before sending C. difficile testing.
      3. Repeated testing for C. difficile should not be performed during the same episode of diarrhea (ie, within 7 days).
      4. Because of the high prevalence of asymptomatic colonization of toxigenic C. difficile among infants and children aged <2 years, testing for CDI is not advised in children aged <1 year, and testing for CDI in children aged 1–2 years should be deferred until other more likely infectious or noninfectious diarrhea etiologies have been excluded.
      5. Most patients who are clinically cured with treatment will continue to have toxigenic C. difficile in their stool for multiple weeks or longer, which is not an indication of treatment failure. Therefore, test of cure should not be conducted, even if a patient is being transferred to another healthcare facility. Facilities should not require repeat C. difficile testing to confirm “clearance” of the organism prior to accepting a patient for interfacility transfer.
    3. Care must be given to balance diagnostic stewardship strategies with also avoiding underutilization of testing that could potentially lead to missed CDI cases. Frequently missed opportunities to test adults with new onset of diarrhea has been reported at some hospitals, but its impact on patient outcomes and/or C. difficile transmission is unknown.Reference Angulo, Pena and Carrico65
    4. Several diagnostic stewardship strategies have safely and successfully reduced misdiagnosis of C. difficile colonization as CDI, with resultant reduction in hospital CDI incidence, CDI antibiotic use, and healthcare charges. These strategies include those below. The comparative effectiveness of these interventions is unknown, although leveraging electronic resources has the advantage of better ensuring consistency in the diagnostic stewardship approach. Hospitals can consider implementation of 1 or more based on cost, resources, and feasibility:
      1. Clinical microbiology assessment of stool consistency by various methods and rejection of formed stools for testing
      2. Education of ordering providers and bedside nurses about appropriate CDI testing decisions
      3. Audit and feedback of CDI testing orders regarding appropriateness of testing
      4. Real-time computerized provider order entry alerts and decision support tools
      5. Electronic medical record tracking of clinically significant diarrhea and laxative use at time of C. difficile testing ordering.

Background on prevention of CDI

Summary of existing guidelines and recommendations

  1. Limitations of existing guidance. Published guidelines on the management of CDI have expanded in recent years, but only some address CDI prevention. Most published studies of CDI prevention are single-center studies with a quasi-experimental (ie, before-and-after or pre- and postintervention) or other observational nonexperimental study design, often performed in response to outbreaks or elevated CDI rates. Often, several concomitant interventions are performed, making it difficult to determine the relative importance of one intervention compared to another. Before-and-after studies are also limited by time-related biases that are difficult to adjust for in the absence of a control group or properly conducted analyses such as interrupted time-series analysis. However, several studies have utilized these techniques, in some cases leading to meta-analyses.
  2. Unique microbiologic characteristics of C. difficile. C. difficile shares many common epidemiologic characteristics with other antimicrobial-resistant gram-positive organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Both the skin and the environment of colonized patients become contaminated, and HCP hands may become contaminated by touching the environment or the patient. The major difference among these 3 organisms is that only C. difficile forms spores. The formation of spores poses unique challenges for hand hygiene and environmental disinfection practices because C. difficile spores are resistant to the bactericidal effects of alcohol and commonly used hospital disinfectants (eg, phenolics and quaternary ammonium compounds).
  3. Strategies focused on unique microbiologic characteristics inconsistently result in CDI prevention. Although alcohol-based hand rub is ineffective at removing or disinfecting C. difficile spores in controlled laboratory experiments, no clinical study has demonstrated an increase in CDI with the use of these products or a decrease in CDI with soap and water.Conversely, several of the studies did identify decreases in MRSA associated with the use of alcohol-based hand rub. Similarly, use of sporicidal methods to disinfect the environment outside outbreak settings has not consistently demonstrated a reduction in CDI with these methods.These data indicate that although the environment can be an important source of C. difficile, indirect transmission by HCP may be the predominant route by which patients acquire C. difficile.
  4. Strategies to prevent CDI (discussed in Section 4) in acute-care settings are generally categorized as follows:
    1. Approaches to minimize C. difficile exposure and colonization through transmission by HCP (eg, hand hygiene and contact precautions)
    2. Approaches to minimize C. difficile exposure and colonization through transmission from the environment (eg, cleaning and disinfection of environment and shared medical devices)
    3. Approaches to reduce the risk of C. difficile colonization and CDI if the organism is encountered by the patient (eg, antimicrobial stewardship).

Infrastructure requirements

  1. Trained infection preventionists. Infection preventionists must have knowledge about risk factors and methods to prevent CDI. They must also be trained in how to categorize CDI cases using surveillance definitions and how to calculate CDI rates.
  2. Methods to systematically identify patients with CDI. Infection preventionists must be able to identify patients with CDI as soon as possible after they are diagnosed, in order to ensure patients are placed in contact precautions in a timely fashion. These data can also be used to calculate CDI rates.
    1. Ability to place patients with CDI on contact precautions:
    2. Contact precautions require the ability to place patients in a private room (preferably) or cohort patients with CDI.
    3. Place materials necessary for adherence with contact precautions (eg, gowns and gloves) in an easily accessible space outside of the patient room. Hand washing sinks should be readily accessible to HCP following doffing of personal protective equipment and/or care of patients with suspected or confirmed CDI.
    4. Place a sign indicating that the patient is on contact precautions outside the patient’s room. This sign should be in English as well as any other language that is commonly spoken in the community or among HCP.
    5. Patients with stool incontinence should preferentially be placed in private rooms. If private rooms are unavailable, use of a dedicated commode or bathroom is recommended.
    6. If it is necessary to cohort patients, place colonized or infected patients in cohorts with the same organism(s). For example, do not cohort patients with CDI who are discordant on VRE or MRSA colonization status.
    7. Dedicated equipment (eg, stethoscopes) should be readily available for HCP. If dedicated equipment is not available, responsibility for who will clean and disinfect equipment, when it will be cleaned and disinfected, and how it will be cleaned and disinfected must be clearly stated.
    8. Have systems in place to facilitate communication among infection prevention and control, admitting, nursing, and environmental service departments, and develop contingency plans for limited bed availability conditions.
  3. An antimicrobial stewardship program is an important part of many quality and safety metrics, including CDI prevention (see Section 4: Essential practices, part 1). A more detailed description of antimicrobial stewardship program infrastructure has been published by Barlam et al.
  4. Provide educational materials for patients, family members, and HCP that include explanations of CDI, why contact precautions are necessary, and the importance of hand hygiene.
  5. Provide adequate resources and training for environmental service personnel to ensure proper cleaning of rooms.

Performance measures

Internal Reporting

These performance measures are intended to support internal hospital quality-improvement efforts and do not necessarily address external reporting needs. The process and outcome measures suggested here (Table 4) are derived from published guidelines, other relevant literature, and the opinions of the authors. Report process and outcome measures to senior hospital leadership, nursing leadership, and clinicians who care for patients at risk for CDI.
  1. Process measures: Perform ongoing measurement of recommended CDI prevention practices to permit risk assessment of CDI.
    1. Compliance with hand hygiene guidelines.
      1. Preferred measure for hand hygiene compliance
        1. Numerator: number of observed proper hand hygiene episodes performed by HCP.
        2. Denominator: total number of observed opportunities for hand hygiene.
        3. Multiply by 100 so that the measure is expressed as a percentage.
    2. If hand hygiene with soap and water is the preferred method of hand hygiene when caring for patients with CDI, also assess proper hand washing technique.
      1. Numerator: number of proper hand washing episodes with proper technique.
      2. Denominator: total number of hand washing episodes observed.
      3. Multiply by 100 so that the measure is expressed as a percentage.
    3. Compliance with contact precautions:
      1. Preferred measure of contact precautions compliance
        1. Numerator: number of observed patient care episodes in which contact precautions are appropriately implemented.
        2. Denominator: number of observed patient care episodes in which contact precautions are indicated.
        3. Multiply by 100 so that the measure is expressed as a percentage
    4. Compliance with environmental cleaning and disinfection:
      1. One specific measure of compliance for use in all hospitals is not realistic. Many hospitals use checklists, environmental rounds, fluorescent markers, and/or ATP bioluminescence to assess the cleaning and disinfection process and cleanliness of equipment and the environment (see Section 4: Essential practices, part 5).
  2. Outcome measures: Perform ongoing measurement of the incidence density of CDI to permit longitudinal assessment of outcomes related to the processes of care. CDI rates are calculated as follows:
    1. Numerator: number of CDI cases in the population being monitored (specific cases included in the numerator depends on the definition used) (Table 3).
    2. Denominator: total number of patient days in the population being monitored.
    3. Multiply by 10,000 so that measure is expressed as number of cases per 10,000 patient days.

External Reporting

There are many challenges in providing useful information to consumers and other stakeholders while preventing unintended adverse consequences of public reporting of HAIs. Recommendations for public reporting of HAIs have been provided by the Hospital Infection Control Practices Advisory Committee (HICPAC), the Healthcare-Associated Infection Working Group of the Joint Public Policy Committee, and the National Quality Forum.
  1. State and federal requirements:
    1. The Centers for Medicare & Medicaid Services (CMS) began requiring acute-care hospitals participating in their Inpatient Prospective Payment System to report laboratory-identified CDI using the NHSN in January 2013.
    2. For information on local requirements, check with your state or local health department.
  2. External quality initiatives. Hospitals that participate in external quality initiatives must collect and report the data if required by the initiative.

Implementation strategies


A broad scope of involvement of multidisciplinary HCP, with engagement of team members who work in the prevention and care of patients with CDI, helps address the complexities involved in implementing a specific CDI control plan based on a risk assessment. Identify and engage a multidisciplinary team as the initial step in implementing a CDI prevention plan:
  1. Involve representation from senior leadership, unit-level leadership, individual HCP, laboratory personnel, pharmacy, environmental services, materials management, and information technology.
  2. Establish goals and embed accountability in the process.


  1. Provide education to HCP, environmental services personnel, executive level leadership, and others that includes at least the following elements: risk factors for CDI, transmission, local epidemiology, patient outcomes, treatment, hand hygiene, contact precautions, management of MDROs, and individual job responsibilities.
  2. Provide information in the native language of the HCP whenever possible.
  3. Identify and implement methods for education and training that provide immersive experiences to enhance critical thinking and decision-making skills (eg, simulations).
  4. Provide education to patients and their families regarding CDI that at least includes the following elements:
    1. The importance of properly performing hand hygiene
    2. General information about CDI, including risk for recurrent CDI, and the difference between colonization and infection
    3. How the facility works to prevent CDI (eg, relevant elements of its CDI prevention program)
    4. Components of and rationale for contact precautions
    5. Risks of transmission to family and visitors while in the hospital and after discharge


Initiate a CDI prevention program:
  1. Perform a CDI risk assessment as a basis for a comprehensive and multidisciplinary intervention.
  2. Define local CDI epidemiology.
  3. Identify the following locations:
    1. High-risk wards
    2. Wards with a high incidence of healthcare facility-onset CDI. Determine whether healthcare facility–onset CDI cases are sporadic or occur repeatedly in the same room(s).
      1. If sporadic, this suggests patient-to-patient transmission from HCP or traveling fomites.
      2. If repeatedly occurring in the same room, this suggests transmission from contaminated environment.
  4. Initiate the prevention program in which there is a high concentration of patients at risk for CDI, such as an ICU or an oncology ward. Pilot test the intervention in 1 patient care location to assess efficacy.
  5. Identify opportunities to improve the following elements:
    1. The system for identifying patients with CDI.
    2. The process for placing patients with CDI in contact precaution rooms that minimizes problems for family members, visitors, and HCP.
    3. Compliance with hand hygiene, contact precautions, and environmental cleaning.
  6. Standardize care processes and practices using bundles, checklists, protocols, and guidelines.
  7. Empower staff to report process defects to appropriate HCP as a means of identifying barriers and facilitating rapid intervention.
  8. Obtain support of the hospital administration and local physician and nursing leadership prior to starting the program.
  9. Assign accountability for adherence to specific departments or functions.
  10. Create redundancy in the system by incorporating use of visual cues as reminders and assistance to recall:
    1. Indicators in the electronic health record that the patient is in contact precautions,
    2. Paper medical records
    3. Signage on the door to the patient room
  11. Replicate the CDI infection prevention and control program in other patient care areas when it is determined that the systems developed are effective.


  1. Conduct performance monitoring to determine whether the intervention is effective by using the following:
    1. Process measures (ie, did you successfully implement your intervention?)
    2. Outcome measures (ie, how well did the intervention achieve the desired outcome?)
  2. Measure both process and outcomes on a regular basis.
  3. Provide feedback to staff.
  4. Provide monitoring data in various formats so it can be posted and broadly distributed.
  5. Incorporate monitoring data into unit-based and department-based measurements so trending over time can be evaluated.
  6. Provide feedback to all levels of personnel regarding process and outcomes, eg, via committee reports and facility newsletters.
  7. Format feedback so respective patient-care areas and individual departments can use data for comparative and goal-setting purposes.
  8. Use feedback to determine specific interventions or improvements for targeted focus.

Recommendation Grading


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.



Strategies to Prevent Clostridioides difficile Infections in Acute-Care Hospitals

Authoring Organizations

Publication Month/Year

April 12, 2023

Last Updated Month/Year

February 14, 2024

Supplemental Implementation Tools

Document Type


Country of Publication


Document Objectives

Previously published guidelines provided comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute-care hospitals to implement and prioritize their Clostridioides difficile infection (CDI) prevention efforts. This document updates the Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission.

Target Patient Population

All patients in acute care or hospital settings

Target Provider Population

All healthcare providers caring for patients in acute care settings

Inclusion Criteria

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

Health Care Settings


Intended Users

Epidemiology infection prevention, nurse, nurse practitioner, physician, physician assistant


Management, Prevention

Diseases/Conditions (MeSH)

D016360 - Clostridium difficile, D003015 - Clostridium Infections


Clostridium difficile, HAI, C diff, Clostridioides difficile, CDI, Cdiff, Clostridioides difficile Infections, HAIs

Source Citation

Kociolek LK, Gerding DN, Carrico R, Carling P, Donskey CJ, Dumyati G, Kuhar DT, Loo VG, Maragakis LL, Pogorzelska-Maziarz M, Sandora TJ, Weber DJ, Yokoe D, Dubberke ER. Strategies to prevent Clostridioides difficile infections in acute-care hospitals: 2022 Update. Infect Control Hosp Epidemiol. 2023 Apr;44(4):527-549. doi: 10.1017/ice.2023.18. PMID: 37042243.


Number of Source Documents
Literature Search Start Date
January 1, 2012
Literature Search End Date
August 1, 2021