Introduction
Clostridioides difficile is a major cause of healthcare-associated diarrhea in the United States, responsible for nearly 500,000 cases of
C. difficile infection (CDI), 30,000 deaths and over $5 billion each year [
1,
2]. One reason that curtailment of CDI remains a major challenge is the high rate of CDI recurrence, which occurs in up to 30% of patients [
3]. Patients with recurrent CDI may need to be subsequently readmitted to a healthcare facility, which presents an opportunity for continued transmission of CDI in the inpatient setting and new infections in susceptible hosts. Data on readmissions following an inpatient stay with CDI, while limited, show that approximately 23% of patients had at least one readmission, with approximately 32% of readmissions carrying a principal diagnosis of CDI [
4]. Patients with a CDI discharge have been found to have a 16 percentage point higher rate of 30-day readmission than patients without a CDI discharge [
5].
Commonly cited risk factors of recurrent CDI include older age and continued use of antibiotics [
6]. Few studies that focus on risk factors of CDI recurrence consider the impact of social determinants of health. Social determinants are increasingly recognized as major contributors to readmissions for chronic conditions like congestive heart failure and myocardial infarction. However, little data exist on the relationship between social determinants of health and outcomes of acute infectious conditions (other than pneumonia-a condition that Centers for Medicare & Medicaid Services (CMS) penalizes for readmission) in developed countries such as the US. Because CDI diagnosis is associated with high rates of recurrence, it is plausible that the rate of readmission following a CDI-related stay would be similar to that for chronic conditions and that socioeconomic disadvantage would be an important contributor to the risk of recurrence and thereby readmission.
Socioeconomic disadvantage likely adversely impacts a CDI patient’s post discharge course. Challenges may include financial constraints to completing the full antibiotic course, especially as the most common treatments for CDI, oral vancomycin and fidaxomicin, can be prohibitively expensive for uninsured patients [
7,
8]. Other challenges may include inability to manage environmental cleaning to reduce re-infection and spore shedding, and lack of resources such as transportation and social support to facilitate follow-up care [
7,
9]. Household crowding, a common indicator of socioeconomic disadvantage, has also been linked to poorer outcomes for infectious disease patients [
10]. As CDI is a disease caused by perturbation of the gut microbiome, factors that impede restoration of the gut microbiome may also affect CDI outcomes. Patients living in socioeconomically disadvantaged neighborhoods have higher rates of comorbid conditions, increasing their contact with the healthcare system and risk of CDI and/or antibiotic exposure. A growing body of literature suggests that diet is a major driver of gut microbiome composition and health [
11,
12]. Patients living in socioeconomically disadvantaged neighborhoods are more likely to live in ‘food deserts,’ where access to healthy, high fiber foods may be limited [
13]. Consumption of low-fiber, highly processed foods has been found to be strongly linked to socioeconomic disadvantage [
14]. As these potential mechanisms impact specific characteristics of CDI, it is likely that disadvantage would adversely affect a CDI patient’s outcomes. Therefore, we hypothesized that socioeconomic disadvantage as measured by residence in a disadvantaged neighborhood would be associated with a higher risk of readmission for CDI patients.
Discussion
We found that living in a disadvantaged neighborhood was associated with increased odds of readmission for patients with a CDI-related index hospital stay and this remained true after adjustment for patient-, stay-, and hospital-level variables. To our knowledge, this is the first study to explore the relationship between social determinants of health as measured by neighborhood disadvantage and risk of readmission for patients with an index CDI-related hospitalization.
Our analyses found that both neighborhood disadvantage and dual Medicare-Medicaid enrollment (a proxy for low-income individuals and common indicator of social risk) were significant predictors of readmission. This suggests ADI captures a dimension of socioeconomic disadvantage that dual Medicare-Medicaid enrollment status and potentially other individual social risk factors cannot. This ability may be driven in part by the impact of neighborhood disadvantage on a patient’s ability to follow post-discharge care and the success probability of that care.
Our findings have implications for clinicians, infection preventionists, and healthcare institutions. For clinicians, the approaches to mitigating risk to CDI patients living in disadvantaged neighborhoods may need to vary from those applied to similar patients with chronic conditions. For example, follow-ups with primary care, potentially using telemedicine resources, might need to be conducted sooner compared to other conditions. Such approaches may need to be conducted in addition to those targeting the impact of neighborhood disadvantage across all conditions. From the infection prevention perspective, placing CDI patients in contact precautions and promoting enhanced hand hygiene practices by healthcare workers is variably effective in reducing transmission, in part because of challenges in high fidelity implementation and breaches in prevention practices. Therefore, preventing readmissions as an upstream intervention is key. Additionally, unlike many chronic conditions, readmission of patients with a contagious disease such as CDI has implications not just for individual patients but for all hospitalized patients including others at risk for readmission. Asymptomatic colonized patients have been shown to contribute significantly to the overall burden of CDI in healthcare institutions, emphasizing the need to prevent unnecessary readmissions [
30]. Preventing readmissions for all patients is also important as a marker for quality and because of the financial implications related to increased rates of readmission. The rates of readmission in this study of Medicare enrollees with an index stay of CDI exceeds the rate of readmission of 17% found in the general Medicare population [
31]. We also found that the length of stay in our study was approximately 3 days longer than that found in the general Medicare population [
32]. As the US healthcare system moves to value-based purchasing with a reduced likelihood that payers will cover costs of readmissions, and the financial penalties to healthcare institutions for CDI, it is important to understand factors that increase readmission risk. The ability to identify specific patients with increased risk for readmission could be a valuable tool to allocate resources such as transitional care programs, intensive case management, and social work to those patients.
Our findings are supported by other studies of readmissions in CDI that report rates of 25–30% readmission and prolonged duration of hospitalization. In a retrospective cohort study of 385,682 initial CDI hospitalizations identified between years 2009 and 2013 in the 4 states included in the State Inpatient Database (AHRQ), 25.7% of patients required readmission; among these, 36.8% had recurrent CDI as the principal diagnosis at the time of readmission [
33]. A study of data from the Healthcare Cost and Utilization Project (HCUP) saw that patients with a primary or secondary diagnosis of CDI had a 30-day readmission rate of 29.1% [
34].
We were not able to determine the extent to which recurrent CDI was the cause of the readmissions. Given the high recurrence rate associated with CDI, it is plausible that recurrent CDI contributed to the readmissions for at least some patients. Prediction models for recurrent CDI have been developed but have had variable performance to consistently predict patients at risk for CDI [
35‐
38]. These models have largely focused on patient level factors such as severity of CDI or comorbidities that may increase readmission risk. Our study examining the relationship between neighborhood disadvantage and readmission extends the knowledge base in this area and offers an opportunity to develop and test interventions targeting social determinants of health in the Medicare-enrolled CDI population. Most other studies of interventions designed to prevent readmissions have focused on acute myocardial infarction, pneumonia, and congestive heart failure [
22,
39]. Infectious conditions (other than pneumonia) have not been included in these interventions. In the case of CDI, where symptoms may be prolonged or recurrent and the implications of readmissions extend beyond the individual patient, additional interventions like those used for chronic conditions may be useful.
To develop such interventions, further research is required to understand the precise mechanisms by which neighborhood disadvantage affects readmission risk in CDI patients. These mechanisms require additional research specifically designed to explore them since those proposed in this study remain conceptual. The actual mechanisms of increased risk, which could resemble those proposed earlier, likely differ somewhat from those affecting chronic conditions because of the infectiousness and recurrence patterns of CDI. Future research efforts should subsequently focus on developing and testing interventions to prevent readmissions of CDI patients living in disadvantaged neighborhoods such as specialized allocation of resources to improve the transition of care after hospitalization and access to follow-up in the outpatient setting. Studies should then examine the impact of these new interventions on CDI rates in healthcare institutions and how these interventions affect other healthcare-associated infections. This is especially important regarding other infections associated with high rates of recurrence, or with extensive or crucial post-discharge care procedures.
Our study has limitations. We did not have patient data on treatment factors, lab tests and vital signs to include in the analyses, any of which could explain the relationship between ADI and readmission risk. Given the lack of data on direct quality measures that may impact the risk of readmission, we could not analyze the quality of care as a marker for readmission in patients with a CDI-related index stay. Our choice of the 85th ADI national percentile as the threshold to split our cohort may have also impacted the findings from our study. However, other studies have used various methods for grouping their cohorts by ADI national percentile, often focusing on the 85th ADI national percentile and up [
22,
40]. Another limitation of this study is the reliance on ICD-9 codes to indicate CDI, rather than lab data. However, ICD-9 codes have been shown to have reasonable sensitivity and specificity for indicating a diagnosis of CDI [
41]. This dataset also does not allow us to identify planned readmissions. Planned readmissions (for non-CDI related purposes) could bias the effect size of any of our independent variables if planned readmissions are not uniformly distributed across our covariates; however planned readmissions in patients with CDI are not common. Focusing this study on Medicare patients may also be a limitation. However, as advanced age is considered a risk factor for CDI susceptibility, it is likely that the Medicare population well reflects the overall CDI susceptible population. Finally, similar to most other studies focusing on the Medicare population, we considered all cause readmissions and did not determine relatedness to CDI [
18,
22]. A justification for this approach is that CDI may influence readmission even if it is not considered as the primary cause of it, as might occur in patients with partially resolved CDI at the time of discharge. Anorexia, dehydration, and weakness related to CDI may exacerbate other chronic comorbidities and lead to readmission. These limitations notwithstanding, this study is among the first to show that neighborhood disadvantage is associated with an increased risk of readmission in inpatients with an acute infectious transmissible condition such as CDI.
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