Clostridium difficile in the Hospital: Infection Prevention Considerations


This chapter provides an overview on Clostridium difficile infection (CDI) and prevention strategies. The main objective of this chapter is to provide understanding on essential CDI prevention measures in acute care and non-acute care settings. There is further discussion on CDI reporting, various measurements of CDI for surveillance purposes, effect on hospital reimbursement and use of multidisciplinary approach for implementation of CDI prevention program.

I. Introduction

Clostridium difficile is a gram positive spore forming anaerobe associated with infection ranging from mild-moderate diarrhea to severe disease with complications such as pseudomembranous colitis, toxic megacolon and death. Clostridium difficile infection (CDI) is recognized as the leading cause of gastroenteritis associated death and the most common cause of healthcare associated infections in the United States. Hospital acquired CDI attributes to increase length of hospital stay, 40% higher expenditure for each diagnosed case, higher readmission rate and mortality. Acute care hospital excess expenditures related to CDI are estimated to be around $4.8 billion. CDI is also being increasingly diagnosed in patients residing in nursing homes and long term acute care facilities, adding to a change in CDI epidemiology including a rise in economic burden, morbidity and mortality.

As an effort to reduce healthcare acquired infection rate, CDI is now recognized as a quality measure for hospitals. Prevention and reduction of spread of CDI is of utmost importance to improve quality of care, patient safety and reduce hospital costs.

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II. Definitions

Clostridium difficile (C. difficile) infection case is defined as clinically significant diarrhea (unformed stools and abdominal cramping) or toxic megacolon with no other identified etiology and presence of at least one or more of the following criteria:

  • Unformed stool sample (conforming the shape of container) positive for C. difficile toxin A and/or B production or detection of toxigenic C. difficile strain by culture or other methods.

  • Pseudomembranous colitis on endoscopic examination or surgery and detected on histopathology.

The surveillance case definition for CDI is:

  • Detection of toxin-producing C.difficile strain on unformed stool OR

  • Presence of pseudomembranous colitis (includes endoscopic examination) or on histopathological examination.

Based on location and timing of symptom onset, the CDI cases are further subjected to different surveillance definitions:

  • Community-associated CDI: CDI occurring >12 weeks after last discharge from a healthcare facility, with symptom onset in community or ≤3 days of hospital admission (day 1 being day of admission).

  • Community-onset, healthcare facility-associated CDI: CDI occurring <4 weeks after last discharge from a healthcare facility, with symptom onset in community or ≤3 days of admission (day 1 being day of admission).

  • Healthcare facility-onset, healthcare facility-associated CDI: CDI symptom onset >3 days after admission to a healthcare facility (day 1 being day of admission).

  • Recurrent CDI: CDI episode occurring ≤8weeks of a previously resolved CDI episode.

  • Indeterminate onset CDI: CDI episode occurring >4 weeks but <12 weeks after last discharge from a healthcare facility.

  • Unknown onset: CDI episode with lack of available data to determine symptom onset and last discharge from healthcare facility.

III. Measurement of CDI for NHSN surveillance

Regular monitoring of CDI rates will help hospitals determine the CDI burden in their facility. It also serves as a tool to monitor effective implementation of CDI prevention program.

The increase in CDI rate, mortality and hospital expenditure has prompted rise in CDI surveillance. CDI surveillance can occur at unit-level or at a facility wide level. CDI surveillance is not performed in Neonatal Intensive Care Units (NICU), Specialty Care Nurseries (SCN), babies in Labor, Delivery, Recovery, Postpartum (LDRP) or Well baby nurseries/clinics.

CDI-positive laboratory assay:

A positive laboratory test result for C. difficile toxin A and/or B, (includes molecular assays [PCR] and/or toxin assays) tested on an unformed stool specimen (conforms to the container)


A toxin-producing C. difficile organism detected by culture or other laboratory means performed on an unformed stool sample (conforms to the container).

A non-duplicate CDI- toxin positive laboratory result is Laboratory-Identified (LabID) Event.

Patients from same location with repeat C.difficile toxin-positive laboratory result within past two weeks of recent C.difficile-toxin positive laboratory result is duplicate CDI positive test. A gap of 14 days period is required with no C.difficile toxin-positive laboratory result to account for another LabID Event.

The CDI LabID Events are further categorized based on date of admission and specimen collection:

  • A LabID event at outpatient facility or within ≤3 days of hospitalization (day 1, 2, 3) is defined as Community-Onset (CO) LabID Event.

  • A CO LabID event collected from a patient discharged within ≤4weeks prior to current date of specimen collection is defined as Community-Onset Healthcare Facility-Associated (CO-HCFA) LabID Event.

  • A LabID event collected >3 days after hospitalization (day 4 onwards) is defined as Healthcare Facility-Onset (HO) LabID Event.

  • Incident CDI assay defined as any CDI LabID event identified >8 weeks after most recent CDI LabID event for the same patient.

  • Recurrent CDI assay defined as any CDI LabID event identified more than 2 weeks but less than 8 weeks from the last LabID event for the same patient.

  • Analysis

C.difficile Incidence rate

Numerator Data: Total number of Healthcare associated (HAI) CDI cases identified during the surveillance month at a particular location.

Denominator Data: Total number of patient days and admissions during the surveillance month at a particular location.

CDI Incidence rate is calculated as number of HAI CDI cases/number of patient days per reporting period x 10,000 = rate per 10,000 patient days.

Standardized Infection Ratio (SIR)

The SIR is calculated for Facility wide inpatient level (FacWideIN) surveillance only and duplicate events are excluded.

SIR is calculated by dividing the number of observed events by the number of predicted events. The number of predicted/expected events is calculated using NHSN data on LabID probabilities during a baseline time period, representing a standard population.

Facility CDI Incidence SIR = Number of all Incident Hospital-onset (HO) CDI LabID Events identified (>3 days after admission to the facility) / Number of expected Incident HO CDI LabID Events

IV. Risk factors for CDI

Understanding the risk factors for CDI is essential to determine appropriate prevention measures to reduce CDI.

Various known risk factors are:

  • Advanced age (>64 years)

  • Antimicrobial use in past 3 months

  • Prolonged hospitalization

  • Prior CDI

  • Immunocompromised patient, HIV/AIDS, ongoing chemotherapy

  • Concomitant co-morbidities e.g., Inflammatory bowel disease (IBD)

Other controversial contributing risk factors

7. Use of PPI or H2 receptor blockers

8. Gastrointestinal surgery or manipulation of GI tract, use of Nasogastric tube

V. Transmission

C.difficle spores are primary means of transmission of CDI due to long term persistence and high resistance to eradication by usual methods such as heat, acidity, regularly used disinfecting agents. Transmission of C.difficile spores can occur from infected or colonized population. Asymptomatic colonization rates are high in elderly patients at nursing homes, long term care facilities, newborns and inpatients in endemic setting.

Direct transmission

  • Person-to-person transmission occurs via feco-oral route.

  • Horizontal transfer on direct contact with patient or body substances of patient infected with CDI or colonized with C.difficile spores.

Indirect transmission

  • On contact with high touch surface areas in C.difficile infected/colonized patients’ room (e.g., bed rails, door knobs, commode).

  • Use of reusable equipments (electronic thermometers, blood pressure cuffs, stethoscopes, commodes, bedpans) between patients.

  • Transmission of spores from healthcare personnel to non-infected patients.

VI. Prevention strategies

Acute care settings

Guidelines for Clostridium difficile prevention

In 2014, Infectious Diseases Society of America (IDSA) and Society for HealthCare Epidemiology of America (SHEA) provided updated guidelines for prevention of CDI. The guideline provides an overview of diagnosis, risk factors for transmission of CDI and recommended strategies to prevent CDI. Other strategies to prevent CDI have been published by American College of Gastroenterology (ACG) and Association for Professionals in Infection Control and Epidemiology (APIC). The CDI prevention guidelines are applicable only in an acute care hospital setting.

CDI prevention strategies provide guidance to prevent acquisition of Clostridium difficile during hospitalization and most importantly prevention of spread of C.difficile spores from infected patients to non-infected patients.

A. Educating healthcare workers, patients and families about CDI.

B. Antibiotic restriction and use of antimicrobial stewardship program to reduce CDI incidence.

C. Appropriate hand hygiene practices prior to entering patient room and washing hands with soap and water after caring for patient with CDI.

D. Use of contact precautions with gloves and gowns while caring for patients diagnosed with CDI.

E. Restrict patients with CDI to private rooms or cohorting patients with CDI diagnosis.

F. Use disposable electronic rectal thermometers and dedicated patient care items and equipments for CDI patients.

G. Environmental decontamination of CDI patient room with sodium hypochlorite solution diluted 1:10 with water.

See Table I and Table II.

Table I.n

CDI Prevention Bundle

Table II.n

Do’s and Don’ts for CDI prevention

A) Education

Essential aspect to reduce spread of CDI includes education and raised awareness among hospital staff.

  • Education of healthcare staff on information about CDI, risk factors for acquisition of CDI, modes of transmission, importance of use of barrier precautions with gloves and gowns and strict hand hygiene practice.

  • Healthcare staff includes nurses, physicians and environmental cleaning staff.

B) Antimicrobial stewardship

Antimicrobial exposure is one of the most important risk factors predisposing to CDI. Use of single dose of any type of antimicrobials in previous 90 days has been associated with CDI. High risk antimicrobials associated with CDI include clindamycin, cephalosporins, ampicillin, fluoroquinolones. Restriction of fluoroquinolones has been most essential due to risk of acquisition of hypervirulent BI/NAP1/027 strain of C.difficile. Hospital interventions with use of antimicrobial restriction or antimicrobial stewardship practice will help reduce incidence of CDI.

  • Restriction of antimicrobial agents associated with high risk for CDI is an important strategy to reduce exposure to these agents.

  • From stewardship aspect, monitoring appropriate indications for antimicrobial use and avoiding use of unnecessary antimicrobial agents is crucial to reduce incidence of CDI.

  • Another stewardship practice includes verification of appropriate treatment of CDI based on severity. If applicable, avoidance of use of concomitant non-CDI antimicrobial agents during CDI treatment.

C) Hand hygiene

The most significant factor contributing to spread of CDI is inappropriate hand hygiene, due to lack of education and practice. Spores are the primary means of transmission of CDI. Most hospital and healthcare facilities have alcohol-based hand rubs for hand hygiene, which have reduced incidence of nosocomial infections except for CDI, as alcohol lacks sporicidal activity. Washing hands with soap and water generates friction, which acts as a sporicidal action. Studies performed have demonstrated superiority of soap and water use compared to alcohol-based interventions. Healthcare workers can contaminate hands while caring for CDI patients or on environmental contact with high-touch surface areas in CDI patient room.

  • Hand hygiene should be performed prior to entering and after exiting the room of patient with CDI, even in absence of patient contact.

  • Hand hygiene education should be provided to healthcare staff, CDI patients as well as patient visitors.

D) Contact precautions

1) Full barrier precautions with use of gowns and gloves are advised while entering the CDI patient room and removing them prior to exiting the room.

2) Use of appropriate personal protective equipment (PPE) is recommended by all healthcare staff prior to entering patient room irrespective of anticipated contact with patient.

3) Isolation precaution sign outside CDI patient room is advised for improving compliance with PPE use.

4) Visitors should be encouraged to use isolation gowns and gloves while in contact with patient, however, this issue is still under debate.

5) Early isolation of patients with diarrhea should be considered prior to availability of C.difficile diagnostic results to reduce environmental contamination.

CDI patients shed spores during active CDI and can continue shedding after diarrhea resolution and treatment completion.

6) IDSA/SHEA guidelines recommend implementing contact isolation precautions until resolution of diarrhea.

7) Contact precautions can be extended until 48 hrs after diarrhea resolution per some expert recommendations.

8) Continuing contact precautions until discharge is considered as special approach.

E) Private rooms

  • Use of private rooms for patients infected with CDI is advised to avoid environmental contamination and contain spread of CDI.

  • In absence of availability of private rooms, cohorting patients with CDI diagnosis in same room is acceptable. Dedicated bedside commodes should be provided to cohorted patients.

F) Dedicated equipments

Sharing of patient care equipment between CDI infected and non-infected patients has resulted in spread of spores. Data from studies have associated contaminated electronic rectal thermometer handles and blood pressure cuffs in horizontal spore transfer.

  • It is advised to use single-use disposable equipment during care of CDI patients.

  • In absence of availability of disposable equipment, dedicated equipment such as thermometers, blood pressure cuffs, and stethoscopes to be restricted to each CDI patient room.

G) Decontamination

C.difficile spores are known to remain viable on surfaces for weeks to months. Horizontal transmission has been documented due to contamination of room with spores from CDI patient and subsequent admission of non-infected CDI patient in same room. Standard environmental decontaminating products used such as quaternary ammonium compounds lack sporicidal activity. Clinical studies and in-vitro data support use of sporicidal decontaminants such as chlorine-containing solution (bleach) and hypochlorite-based solutions.

  • Use of sodium hypochlorite solution 1:10 diluted with water or Environmental Protection Agency (EPA)-approved sporicidal agent is advised for daily cleaning of CDI patient room.

  • Daily/terminal cleaning of environmental and high-touch surface areas is advised to effectively disinfect CDI patient room.

  • Education provided to environmental service workers on use of sporicidal agents and cleaning of high-touch surface areas.

  • Healthcare staff should use chlorine-based (bleach) wipes for disinfection of reusable personal equipments (e.g., stethoscope) in between CDI infected and non-infected patients.

  • There is insufficient evidence to support use of no-touch technologies (UV light and Hydrogen peroxide fogging) for room cleaning and disinfection.

Non-acute care settings

There is a rising prevalence of CDI in patients in non-acute care settings such as nursing home and long-term care facilities (LTCFs). There are multiple explanations for higher CDI prevalence in these settings.

  • High likelihood of patients with CDI to be discharged to non-acute care facilities.

  • Majority of admitted patients are elderly, one-third have bowel incontinence and 50% are asymptomatic carriers of C.difficile.

  • Lack of adequate antimicrobial stewardship and isolation practices.

  • Delayed identification of CDI patients due to unavailability of rapid CDI diagnostic testing.

In non-acute care setting, bundled approach with infection prevention and antimicrobial stewardship practice is of utmost importance for prevention of CDI.

  • Need for effective communication between acute care hospitals and non-acute care settings during transition of care. This will help in early identification of CDI patients on admission to allow use of isolation precautions in timely fashion.

  • Initiation of antimicrobial stewardship practice in non-acute care setting to reduce CDI incidence.

  • Education of healthcare staff on CDI diagnosis, treatment and prevention methods.

  • Early identification and access to laboratory for immediate and accurate diagnosis of CDI.

  • Strict compliance on use of soap and water for hand washing, isolation precautions and environmental cleaning with sporicidal agents during care of patients diagnosed with CDI.

Strategies with weak evidence

Other strategies to prevent CDI have been studied. However, there is inadequate evidence to support practical implication of these strategies.

H) Proton pump inhibitor use

Use of acid suppressants such as H2 blockers and proton pump inhibitors (PPI) has been associated with increased risk for CDI. The association is still controversial as there have been studies performed which did not find any such association. Food and Drug administration has issued safety notification on elevated risk for CDI after PPI use.

  • Caution should be practiced while prescribing PPI.

  • PPI use should be restricted in patients with indication for acid suppression.

  • If possible, PPI use should be avoided in patients at high risk for acquisition of CDI.

I) Probiotic use

Use of probiotics to prevent CDI has been a topic of debate. A meta-analyses study concluded reduced risk for CDI with probiotic, however, it is not applicable due to several limitations. Randomized controlled trial performed with placebo and probiotics did not demonstrate any statistically significant difference in reduction of CDI incidence. Evidence supports use of probiotics Lactobacillus rhamnosus GG and Sacchromyces boulardii probiotics for reducing antibiotic associated diarrhea but there is insufficient evidence to support its use in prevention of CDI.

  • Use of probiotic for prevention of CDI is not recommended due to lack of strong evidence.

J) Vaccination

A promising strategy in future for prevention of CDI is vaccination with antibiodies against C.difficile toxins. After effective evidence to support use of vaccination with toxin B in animal studies, phase 3 trials are in process to demonstrate benefit of vaccination in CDI prevention.

  • No recommendation can be provided for use of vaccination against C.difficile toxins.

K) Laboratory alert system to identify CDI-positive patients

Admission-based laboratory alert system can help identify patients with history of CDI. The alert will notify Infection control personnel or clinician for early isolation of patients with admission diagnosis suspicious for CDI.

L) Nurse driven protocol for early identification

Universally, nurses have more interaction and contact with patients resulting in early identification of CDI patients compared to physicians.

  • Implementation of nurse-driven protocol for ordering diagnostic testing for detection of CDI will lead to early diagnosis and timely isolation of patients with diarrhea.

  • This measure involves education of nurses on identification of appropriate clinical signs and symptoms for diagnosis of CDI and distinguishing CDI from other causes of diarrhea.

VII. Measures during Outbreak setting

Rise in CDI has been documented as a part of outbreak or hyperendemic settings. There has been no clear definition for these terms.

  • Outbreak being defined as rise in CDI cases more than usual expected cases due to chance alone.

  • Hyperendemic rate being persistently elevated CDI rates compared to previous years or in comparison to similar healthcare facilities.

Studies have been conducted during CDI outbreaks with interventions performed as a bundled approach. The basic prevention strategies remain backbone for CDI prevention. In outbreak/hyperendemic setting additional measures are performed as a special approach to reduce transmission and incidence of CDI.

Special additional components in bundled approach:

  • Strict hand-hygiene with soap and water is recommended. Hand-hygiene should be performed prior to patient contact and after removal of gloves.

  • Universal gloving is effective means for reducing hand contamination for CDI prevention.

  • Environmental decontamination should be performed with sodium hypochlorite solution (1:10 dilution with water) or Environmental protection agency (EPA)- registered disinfectant.

  • Physicians, Infection Control Practitioners, Healthcare staff should have high suspicion for diagnosis of CDI in any patient with diarrhea and abdominal cramping. Immediate isolation and CDI testing with high sensitivity and rapid turn-around time should be ordered.

  • Due to risk of continued shedding of C.difficile spores and contaminating environment, consideration should be given for isolating patient for prolonged duration after being asymptomatic from diarrhea until discharge.

  • Strict antimicrobial stewardship intervention with restriction of high-risk antimicrobials (clindamycin, cephalosporins, carbapenems and fluoroquinolones).

  • Regular monitoring of compliance to bundled strategies should be performed.

  • Regular reporting and discussion should be conducted with leadership and healthcare workers to monitor and detect gaps in CDI prevention strategy.

  • Use of fluorescent markers for monitoring cleaning or Adenosine Triphosphate (ATP) bioluminescence can be used to measure organic material on surfaces. This strategy has proved to be effective to monitor compliance with environmental cleaning and disinfection.

VIII. Reporting

  • Surveillance reporting can be performed with traditional infection surveillance reporting or laboratory-based reporting.

  • Traditional reporting involves chart review to meet the surveillance definition for CDI. Laboratory-based definition is based on positive stool testing for C.difficile and/or its toxins, without chart review

  • Laboratory results of C.difficile testing should be reported on a daily basis to designated Infection prevention personnel.

  • Internal reporting of compliance to components of CDI prevention program should be performed with senior leadership, nursing leadership and clinicians as hospital quality improvement measure. Examples of components include hand hygiene, contact precautions use, environmental cleaning and disinfection.

  • Since January 2013, Centers for Medicare and Medicaid services (CMS) requires acute care hospitals participating in inpatient prospective payment system to report CDI LabID events data at facility wide inpatient level (FacWideIN) to NHSN for fulfilling CMS’s Hospital Inpatient Quality Reporting (IQR) Requirements.

  • Public reporting of US hospital-onset CDI rates is a risk-adjusted metric reported as standardized infection ratio (SIR). Risk adjusted metric is adjusted based on type of C.difficle testing performed, prevalence of CDI on admission, hospital size, and medical school affiliation.

  • State or local health department reporting can be performed per individual state or local policy.

  • Reporting for C. difficile LabID events is performed by location and separately and independently of Events reported using the C. difficile Infection Surveillance/Hospital acquired infection reporting.

IX. Reimbursement

In order to improve high-quality patient care, CMS recently reclassified quality domains and updated quality reporting programs (QRP) for beginning of the fiscal year (FY) 2017. CMS released final regulation for new Value-based purchasing (VBP) program which affects hospitals with inpatient prospective payment system (PPS). For all the acute care hospitals, Hospital-onset C.difficile infection outcome measures will be added to the Hospital VBP program for FY 2017 payment determination. Similarly for Inpatient rehabilitation facilities, Hospital-onset CDI outcome measures will be added to the QRP for FY 2017 payment determination. A 2% reduction in payment will begin from FY 2017.

XI. Accreditation and Accountability


Joint Commission aims to reduce the risk of health care-associated infections. Rise in C.difficile infection as the most common hospital acquired infection prompted Joint Commission to identify CDI as one of National Patient Safety Goals. Joint Commission has issued a new Medication Management standard addressing antimicrobial stewardship (MM.09.01.01) applicable to all hospitals, critical access hospitals and nursing home centers effective January 1, 2017. The elements of performance in this standard requires all hospitals to implement antimicrobial stewardship plan, use organization approved protocols such as Antibiotic Formulary Restrictions and Assessment of Appropriateness of Antibiotics for Care of patient with C.difficile infection.


Lack of accountability by senior leader or hospital directors results in inconsistent and ineffective implementation of infection prevention program.

  • A multidisciplinary approach with team involving senior and unit level leaders, infection control and prevention leaders, healthcare providers, laboratory personnel, pharmacy, environmental services, material management and information technology should be involved for planning infection prevention program. Each team member/specific group should be accountable for specific prevention measure.

  • Leadership including chief executive officer, other senior leaders should be involved in decision making process of CDI prevention program.

  • Senior leadership is accountable for providing support to infection prevention and control program and should provide resources such as healthcare personnel, education, equipments for facility wide application of prevention program.

  • Infection prevention and control leadership should monitor implementation of prevention program, perform analyses of changes post implementation and periodically report to leadership for determining measures for improvement in the prevention program.

  • Senior leader and Unit leaders are accountable for training and educating about CDI prevention program to healthcare personnel, patients and families.


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This article originally appeared on Infectious Disease Advisor