A Tiered Approach for Preventing <i>Clostridioides difficile</i> Infection
Authors: Jeffrey M. Rohde, Karen Jones, Norma Padron, Russell N. Olmsted, Vineet Chopra, Erik R. Dubberke
Journal: Annals of Internal Medicine (2019)

Supplement: STRIVE1 October 2019A Tiered Approach for Preventing Clostridioides difficile InfectionFREEJeffrey M. Rohde, MD, Karen Jones, RN, BSN, MPH, Norma Padron, PhD, MPH, MA, Russell N. Olmsted, MPH, CIC, Vineet Chopra, MD, MSc, and Erik R. Dubberke, MD, MSPHJeffrey M. Rohde, MDUniversity of Michigan Medical School, Ann Arbor, Michigan (J.M.R., K.J.)Search for more papers by this author, Karen Jones, RN, BSN, MPHUniversity of Michigan Medical School, Ann Arbor, Michigan (J.M.R., K.J.)Search for more papers by this author, Norma Padron, PhD, MPH, MAHealth Research & Educational Trust, American Hospital Association, Chicago, Illinois (N.P.)Search for more papers by this author, Russell N. Olmsted, MPH, CICIntegrated Clinical Services, Trinity Health, Livonia, Michigan (R.N.O.)Search for more papers by this author, Vineet Chopra, MD, MScUniversity of Michigan Medical School and Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan (V.C.)Search for more papers by this author, and Erik R. Dubberke, MD, MSPHWashington University School of Medicine, St. Louis, Missouri (E.R.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-3444 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail According to the Centers for Disease Control and Prevention (CDC) Emerging Infection Program surveillance, more than 450 000 initial episodes of Clostridioides difficile infection (CDI) occur annually in the United States (1, 2). Although CDI occurs in both community and acute care settings, the risk for CDI is much higher in the hospital. Indeed, health care–associated exposure or infection is thought to be the most common source of community CDI, with greater than 80% of patients with community CDI reporting contact with health care (3). In the acute health care setting, C difficile has emerged as the most common causative agent of health care–associated infections (HAIs) (4, 5). Between 2001 and 2010, the incidence of CDI among hospitalized patients nearly doubled, rising from 4.5 to 8.2 cases per 1000 adult discharges (6). Despite recent successful reduction in prevalence of other HAIs, CDI rates have remained largely unchanged since 2010 (5).Clostridioides difficile infection substantially contributes to overall morbidity and mortality: It is associated with increased readmission rates, admission to long-term care facilities, and more than 29 000 deaths in the United States annually (7, 8). Furthermore, CDI among hospitalized patients is responsible for between $4 and $6 billion in excess U.S. health care expenditures annually, and recently, hospitals are not receiving additional reimbursement to cover these added costs (9, 10). Given this burden on patient safety and financial resources, numerous efforts have been made to prevent CDI in the acute care setting (11).There are 3 primary approaches to reducing CDI rates in the acute care setting: 1) prevent exposure to C difficile spores, 2) minimize disruption to and preserve intestinal microbiota, and 3) improve diagnostic stewardship when it comes to testing for CDI. The first 2 measures aim to disrupt the nosocomial spread of C difficile and progression to infection. The third aims to balance early recognition of patients with CDI against the need to minimize overdiagnosis in patients who are colonized, but not infected, with this pathogen (12).To assist acute care facilities that still struggle with HAIs, including CDI, a nationwide quality improvement project was initiated in 2016. This article summarizes the development of a tiered approach to CDI prevention interventions as part of this project and reviews the supporting evidence behind those recommendations.Project StructureFunded by the CDC after the 2012 Ebola outbreak, STRIVE (States Targeting Reduction in Infections via Engagement) is a prospective, nonrandomized, clustered quality improvement project designed to reduce HAIs, including CDI, in acute care settings. Four cohorts of hospitals and long-term acute care hospitals with a high burden of CDI were targeted for recruitment in STRIVE on the basis of National Healthcare Safety Network data from 2015. A high burden of CDI was defined as a cumulative attributable difference (CAD) above the first tertile (the top third in the nation) as calculated by the CDC. The CAD is the number of infections needed to be prevented in order to reach a specified standardized infection ratio goal. A national project team was formed to develop an overarching structure to assist facilities in the application of evidence-based practices aimed at HAI reduction.To develop the CDI intervention for STRIVE, the national project team reviewed published systematic reviews and relevant practice recommendations and guidelines. For CDI specifically, this included the 2010 Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) clinical practice guidelines (13) as well as the 2017 update (14). Both of these documents used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to evaluate the quality of evidence and determine the strength of recommendations, which was used by the project team when selecting strategies. In addition, the 2014 American College of Gastroenterology guidelines for diagnosis, treatment, and prevention of CDI (15), and the 2014 SHEA/IDSA practice recommendations for strategies to prevent CDI in acute care hospitals were reviewed when developing our intervention (16).In contrast to the high-quality data from randomized, controlled trials directing the treatment of CDI, evidence informing the prevention of CDI is sparse, with most studies representing single-center, nonrandomized quasi-experimental designs (16). Also, many CDI prevention strategies are implemented as part of a bundle or during an outbreak, making it difficult to attribute effectiveness of an intervention to any one particular component (17).A summary of the literature review was presented to national experts at the project's kick-off meeting in 2016. After discussion among infection prevention specialists, implementation science experts, environmental services specialists, physicians, and nurses, the focus was first placed on “horizontal” (or foundational) infection prevention practices. The CDI tier elements were then further advanced and refined by the interdisciplinary STRIVE content development committee.Tier FrameworkMany infection prevention practices are not exclusive to specific HAIs; rather, they are necessary to form the foundation for effective HAI prevention work. Such horizontal infection prevention practices are intended to be applied broadly in acute care facilities. Instead of being pathogen-specific, they have the potential to affect several different HAIs. For the STRIVE project, the chosen foundational elements were hand hygiene (HH), personal protective equipment (PPE), environmental cleaning and disinfection, antimicrobial stewardship, building a business case for infection prevention, uber-adaptive infection prevention practices, competency-based training, audits and feedback, and patient and family engagement (18). For each of these domains, short, on-demand educational video modules (www.cdc.gov/hai/) were created by content experts and distributed to the participating hospitals. Four elements (HH, PPE, environmental cleaning and disinfection, and antimicrobial stewardship) that were thought to be crucial to CDI prevention were further expanded upon and emphasized in relation to CDI prevention.A tiered approach was chosen to prioritize interventions that are supported by stronger, higher-quality evidence, have a potential greater impact, or are less burdensome, with more intensive interventions being reserved for tier 2. Informed by the literature review, tier 1 CDI prevention interventions focus on minimizing disruption of intestinal microbiota, preventing exposure to C difficile spores, and improving diagnostic stewardship. An overview of the final tiered STRIVE approach to CDI prevention is presented in the Figure. A description of each component of the tiered intervention and review of the evidence supporting them follows.Figure. Tiers of interventions to prevent CDI.CDI = Clostridioides difficile infection; EPA = Environmental Protection Agency; GPS = guide to patient safety; TAP = Targeted Assessment for Prevention. Download figure Download PowerPoint Tier 1 PracticesTier 1, Intervention 1: Antimicrobial StewardshipThe first intervention recommended for tier 1 was to implement or reinforce existing antimicrobial stewardship programs with a particular focus on interventions specific to CDI. With approximately 50% of patients in the acute care setting exposed to antibiotics and studies indicating that between 30% and 50% of those antibiotics are unnecessary or inappropriate (19–21), disruption of the microbiota via antibiotics is the most significant risk factor for developing CDI (22, 23). Hence, antimicrobial stewardship remains the single most important intervention for preventing CDI and was prominently supported in all of the clinical guidelines that were reviewed (13–16, 24). Several systematic reviews and meta-analyses have supported the effectiveness of antimicrobial stewardship programs (ASPs) in preventing CDI (25–27). Although meta-analyses vary in the type of studies and ASPs included, ASP implementation has been consistently associated with a 32% to 52% reduction in CDI incidence. In addition, ASPs with a particular focus on antibiotics that are considered high risk for CDI (third-generation cephalosporins, fluoroquinolones, ampicillin, and clindamycin) are more effective in preventing CDI (28). In one single-center study performed during a CDI epidemic, an ASP focused on high-risk antibiotics was associated with a 60% reduction in CDI incidence (28).Improving the appropriateness of antibiotic use not only reduces an individual's chances of getting CDI but may also prevent collateral transmission risk in hospital wards (29). The effect of antimicrobial stewardship at the hospital or ward level is thought to stem from a decrease in shedding of C difficile spores in asymptomatically colonized patients who develop antibiotic-associated diarrhea while in the acute care setting. Stewardship may thus lead to “herd immunity”: If there are fewer patients at risk for CDI, fewer will develop CDI and shed high levels of C difficile spores (30, 31).To assist hospitals with implementation, the STRIVE team also highlighted additional potential benefits of ASPs, including prevention of multidrug-resistant organisms, reduction of antibiotic-associated adverse events, prevention of HAIs, and reduction of costs (27, 32, 33). In addition, the CDC 2014 recommendation that all acute care hospitals implement an ASP and the 2017 Joint Commission antimicrobial stewardship standard mandate that all critical access hospitals have an ASP were emphasized. To support generating a standard infrastructure to create effective ASPs, we recommended the CDC core elements of hospital antimicrobial stewardship programs (leadership commitment, accountability, drug expertise, action, tracking, reporting, and education) (34).Tier 1, Intervention 2: C difficile TestingPromoting early and appropriate CDI testing was the next recommended intervention. Diagnosis of CDI is clinical, and laboratory tests alone cannot discriminate between colonization and CDI. Misdiagnosing colonization as infection can directly increase CDI rates particularly in the acute care setting, where as many as 15% of patients are asymptomatically colonized with toxigenic C difficile (35–37). With the variability in the performance of enzyme immunoassay testing for glutamate dehydrogenase and C difficile toxins, as well as amplified detection of colonized patients with nucleic acid amplification, guidelines and experts recommend a multistep approach combining the 2 types of tests (3, 37). In addition, repeating tests, ordering multiple tests, and tests for cure were all not recommended. The team recommended that CDI testing be paired with “stool stewardship,” or only testing patients with clinically significant diarrhea (3 or more loose stools per day for at least 24 hours) without another likely explanation (for example, laxatives) for their symptoms (13). Finally, educating health care personnel on clinical features, transmission, and epidemiology of CDI and processes for appropriate testing was emphasized. Studies at single centers have shown that improved stewardship of C difficile testing such as this is associated with improved performance on CDI metrics (38, 39).The national team recognized the tension in balancing diagnostic stewardship with the need to quickly identify patients with CDI. Rapid identification of patients with CDI can diminish environmental contamination and transmission to other patients. Tier 1 thus recommended processes to ensure early detection of patients with CDI as well as automated laboratory alerts to notify staff of positive results. In a single-center study done at the Cleveland Veterans Affairs Medical Center, a process with laboratory notification of clinicians complemented by formation of a CDI stewardship team led to substantial reductions in delays in treatment (40).Tier 1, Intervention 3: Hand Hygiene and Glove UseThe next recommended intervention focused on preventing transmission of C difficile spores through HH and strict glove use. In the acute care setting, the hands of health care providers are a common mode of pathogen transmission, playing a part in an estimated 20% to 40% of HAIs (41). Proper HH technique using alcohol-based hand rubs (ABHRs) or soap and water is effective in decreasing bacterial counts on the hands by 3 or 4 log (42, 43). For most pathogens, ABHRs appears to be more effective, accessible, and efficient in reducing bacterial counts on the hands compared with soap and water (44, 45). This is not the case for C difficile spores, which can persist in environments for months, are notoriously difficult to kill with disinfectants, and regularly contaminate the hands of health care workers (46). In a study of 66 health care workers, 24% had detectable C difficile spores after routine care of patients with CDI (47). Furthermore, nonclinical studies where volunteers' hands were experimentally contaminated by nontoxigenic C difficile spores suggest that neither ABHR nor HH with soap and water is particularly effective in removing CDI spores (48, 49). In a study of 10 volunteers, soap and water was superior to ABHR at mechanically removing spores (2-log reduction versus 0.06-log reduction), with ABHR being no different than no HH (50).Further confounding this issue is the overall poor rates of compliance with HH in acute care facilities, where about one half of all HH opportunities are missed (51). Recognizing these challenges, the national team recommended competency-based training for staff based on the World Health Organization 2009 guidelines for HH, including the 5 Moments for Hand Hygiene and the CDC's Clean Hands Count campaign (22). In addition, donning PPE—particularly gloves upon entry to a patient's room—was emphasized as a means to prevent contamination, because this has been associated with decreased CDI rates. In a prospective study of 3 hospital wards, an intervention on one unit aimed at increasing glove use by health care providers resulted in a decrease in CDI from 7.7 to 1.5 cases per 1000 patient discharges, whereas the other 2 control units noted no change in CDI rates (52).Tier 1, Intervention 4: Contact Precautions and PPEInitiation of contact precautions when patients test positive for CDI and maintaining such precautions for the duration of CDI illness was the next tier 1 recommendation. Contact precautions include the donning and doffing of gowns and gloves (53). Although glove use is particularly important, gowns also play a protective role in preventing CDI, because C difficile spores have been isolated on hospital workers' uniforms after their shift (54). Proper use of contact precautions and PPE can protect health care workers and patients from HAI, but suitable technique is often lacking (55). In one study using fluorescent lotion, 46% of 435 glove-and-gown removal simulations were found to be associated with contamination of skin and clothing of participants (56). Another important aspect of contact precautions is dedicated medical equipment. In one study, 20% of electronic rectal thermometer handles were found to be contaminated with C difficile; changing to disposable thermometers led to a significant decrease in CDI rates (57). In addition, data indicate that up to 14% of stethoscopes become contaminated after being used to examine a patient with CDI (58). Therefore, informed by the 2007 CDC isolation precaution guidelines, use of dedicated or single-use patient equipment and supplies, use of single rooms or cohort patients with CDI, and use of full barrier PPE were emphasized in tier 1. Finally, routine competency-based training for proper use of PPE with audits and feedback were also recommended.Tier 1, Intervention 5: Environmental Cleaning and DisinfectionNumerous studies have examined the contribution of contamination of health care environments in hospitals and long-term acute care hospitals to HAI, including CDI (59, 60). Proper environmental cleaning and disinfection can substantially reduce environmental contamination and the associated risk for transmission and infection of patients (61, 62). However, in practice, cleaning and disinfection practices vary widely, with studies that indicating only 50% of surfaces are regularly cleaned (63). In addition, high-use areas, such as bedside commodes and in-room sinks, are regularly contaminated and are frequently not cleaned or disinfected (63). More recently, increased risk for acquisition of C difficile has been associated with treatment of the prior occupant of the room with antibiotics (64). Therefore, the national team recommended partnering with environmental services to ensure that cleaning and disinfection processes were clearly defined and targeted high-touch surfaces (such as over-bed tables, bedrails, chairs, sinks, and commodes), patient care equipment that directly touches patients (such as thermometers, stethoscopes, and blood pressure cuffs), and surfaces touched by health care workers (such as doorknobs, intravenous infusion pumps, and computers). Furthermore, these efforts need to be supported with routine competency-based training, audit, and feedback.Tier 1, Intervention 6: Monitoring of CDI Rates and FeedbackDeveloping and encouraging a culture of continuous improvement is important for all HAI prevention efforts. One of the first steps in this process is gathering and sharing performance data. These data can help institutions focus enhanced interventions in areas with high incidence of CDI. Rates of CDI, specific high-risk antibiotic use, adherence to contact precaution protocols, and HH compliance all play a role in CDI prevention and can vary widely across different units in the same hospital. Monitoring these data and providing them to frontline providers further supports the other tier 1 interventions and makes them more effective (27).Tier 2 PracticesIf a facility's CDI rates remain elevated after tier 1 interventions were effectively implemented, tier 2 interventions could be introduced. These more intensive practices are generally more burdensome from a human capital perspective and require more resources. Therefore, the decision to proceed with tier 2 interventions was left to each partnering facility, and no specific target CDI rate was recommended by STRIVE beyond the CAD evaluation. After tier 1 interventions were reviewed and supported, tier 2 recommendations focus on the prevention of contamination and transmission of C difficile spores in the acute care environment.Tier 2, Intervention 1: Guide to Patient Safety and Targeted Assessment for Prevention StrategyThe first tier 2 intervention is the CDI guide to patient safety (GPS) (65). The GPS is a concise, self-administered troubleshooting tool that seeks to aid infection prevention teams in understanding what elements may be lacking in their effort to reduce CDI. It consists of 11 yes/no questions and is modeled after the validated Catheter-Associated Urinary Tract Infection GPS (66). The specific CDI GPS questions are published elsewhere (65). The CDI GPS is designed to highlight gaps in current CDI prevention practice such that specific strategies and resources to overcome barriers and challenges can be implemented. The CDI GPS provides tailored resources to help overcome barriers. For example, if an institution answers that its laboratory does not reject formed stools submitted for CDI testing, links to best practices in this topic are provided. The national team emphasized that the CDI GPS was to be performed before implementing other tier 2 CDI prevention strategies.The team also highlighted the CDC's Targeted Assessment for Prevention (TAP) strategy as another self-assessment tool aimed at helping facilities identify and address gaps in HAI prevention efforts. The CDI TAP strategy has 5 components: running TAP reports based on National Healthcare Safety Network data, targeting specific units on the basis of those reports, communicating TAP report data to engage leadership and clinicians, assessing the gaps in infection prevention with TAP assessment, and implementing the appropriate infection prevention strategies with advice from TAP guides and resources (67).Tier 2, Intervention 2: Enhanced PracticesShould CDI rates remain high despite optimal implementation of tier 1 interventions and completion of the GPS and TAP strategy, the next step recommended was implementation of expanded contact precautions. Specifically, sites were recommended to initiate contact precautions as soon as C difficile tests were ordered (for symptomatic patients) and to continue these precautions until discharge as opposed to stopping them after resolution of diarrhea (14). Prolonging contact precautions is resource-intense but can help to prevent CDI spread by expanding the window of protection (16). Even after resolution of diarrheal symptoms, patients with CDI often continue to be asymptomatic C difficile carriers and can lead to environmental contamination. Cultures of acute care environments of asymptomatic carriers have showed a lower rate of environmental contamination than patients with active diarrhea (29% vs. 44%) (68). However, environmental contamination by asymptomatic carriers does occur. Currently, the risk for transmission from asymptomatic contamination remains controversial (69, 70). In one study of 35 asymptomatic carriers, high rates of environmental contamination (59%) and skin contamination (61%) were observed, and this contamination was easily transmitted to investigators' hands (70). In addition, other factors (such as stool incontinence) probably play a role in rates of contamination and are not well studied (71). Nevertheless, given the context of elevated rates despite tier 1 steps, expanded protection was felt appropriate and implemented as a first tier 2 step.The next tier 2 step focused on intensifying adherence to environmental cleaning and disinfection. Potential strategies for this step include the use of fluorescent markers to ensure that high-contact areas are effectively cleaned, and the use of Environmental Protection Agency–approved sporicidal or no-touch disinfectant, such as ultraviolet germicidal irradiation (72–74). To further support this practice, audit checklists, team rounding, and routine partnering with environmental services personnel to understand challenges and barriers were encouraged. Finally, real-time feedback on HH adherence, development of frontline physician and nurse champions, targeted competency-based training for health care workers, and inclusion of patients in HH education were recommended.ConclusionAs part of a nationwide quality improvement project supported by the CDC and Health Research & Educational Trust, we developed a tiered approach to support acute care facilities' efforts in the prevention of CDI. Several of the proposed CDI prevention interventions are foundational to infection prevention and have the potential to impact other HAIs. Tier 1 interventions were first-line, high-quality evidence-based recommendations for preventing CDI. A GPS was developed to support interventions and was followed by enhanced support of efforts to prevent exposure of patients to C difficile spores. 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