A Tiered Approach for Preventing Clostridioides difficile Infection

According to the Centers for Disease Control and Prevention (CDC) Emerging Infection Program surveillance, more than 450000 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 careassociated 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 careassociated 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 29000 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 Structure Funded 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 Framework Many 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. Tier 1 Practices Tier 1, Intervention 1: Antimicrobial Stewardship The 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 (1921), 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 (1316, 24). Several systematic reviews and meta-analyses have supported the effectiveness of antimicrobial stewardship programs (ASPs) in preventing CDI (2527). 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, Intervent