Clostridioides difficile infection (CDI), previously known as Clostridium difficile (C. difficile), is colonization and infection of the colon following normal flora disruption. CDI produces toxins that result in diarrheal illness and colitis (Johnson et al., 2021; Kelly et al., 2021). Colonization of C. difficile in individuals may not lead to active infection, resulting in asymptomatic carriage, with an estimated 4%-15% of healthy adults as carriers (Kelly et al., 2021). Asymptomatic carriage is estimated to be 21% in hospitalized individuals and may be up to 30% for residents in long-term care facilities (Kelly et al., 2021).
Background
Historically, CDI was felt to be a hospital-acquired infection (Guh et al., 2020). The national burden of hospital-acquired CDI infection decreased by 36% from 2011 to 2017, but community-acquired infection remained the same during this period (Guh et al., 2020). Antibiotic exposure, healthcare facility exposure, and older age are well-known risk factors; however, compromised immunity, liver and renal disease, cardiac disease, chemotherapy, prolonged hospitalization, prior gastrointestinal procedures, intensive care admission, recent hospitalization, ventilatory support, enteral feedings, malnourished states, White race, and hypoalbuminemia have also been shown as risk factors for CDI (Kelly et al., 2021; Sams & Kennedy-Malone, 2017).
Between 2001 and 2012, recurrent CDI increased 188%, and CDI incidence annually was 43% (Kelly et al., 2021); however, CDI cases have shown a decrease between 2011 and 2017 in the United States, and long-term care facilities have reported a 55% decrease in incidences from 2011 to 2015 (Kelly et al., 2021), felt to reflect the targeted approach toward healthcare-acquired infections in hospitals and other healthcare establishments. Multiple disease processes may affect the older adult and lead to hospitalization. The bacterial illness C. difficile in this vulnerable population has the potential to lead to prolonged hospitalization, adverse outcomes, and possibly death.
Adults 65 years and older are at increased risk for CDI and severe infection, with advancing age correlating to increased difficulties with successful treatment. The decreased immunity in older adults has been felt to contribute to the complicated disease process (Dumic et al., 2019). Age-related changes in the intestinal microbiota of older adults increase the risk for severe CDI, and a decrease in functional status is independently associated with poor outcomes (Dumic et al., 2019).
Recurrent CDI has been defined as a reoccurring episode of CDI within 8 weeks of the previous occurrence (Song & Kim, 2019). The most common risk factors identified with the development of recurrent CDI are advanced age, subsequent antibiotic therapy especially in patients who received fluoroquinolones, patients with chronic kidney disease (Chilton, Pickering, & Freeman, 2018; Fernandez-Cotarelo et al., 2019) and patients taking proton pump inhibitors (PPIs), although there have been studies that have refuted this finding (Hopkins & Wilson, 2018).
Studies have shown that for patients who fail initial treatment for CDI, 40%-60% will have a second recurrence, with the majority of the recurrence from the original strain (Hopkins & Wilson, 2018). The likelihood of recurrence increases after the first recurrence (Madoff, Urquiaga, Alonso, & Kelly, 2020), although it remains often difficult to discern an actual relapse versus an actual reinfection (Chilton et al., 2018). Collins, Ayturk, Anderson, and Santry (2015) found that 29% of patients who had been hospitalized with CDI were admitted within 2 weeks, and 56% were readmitted within 30 days. Comorbidities in this sample of persons 65 years and older increased the risk of readmission for CDI, and antibiotic use was the greater predictor for readmission in those who had not been hospitalized between an initial and recurrent admission (Collins et al., 2015). Recurrent CDI infections have been linked with increased mortality often within 6 months of the initial infection (Olsen, Yan, Reske, Zilberberg, & Dubberke, 2015).
The current study aimed to explore the characteristics of hospitalized adults 55 years and older with initial CDI and recurrences by extracting routinely documented data in the electronic health record (EHR).
Methods
A retrospective cohort study was conducted with the goal of capturing patients hospitalized with CDI as identified by International Classification of Diseases (ICD)-9/10 diagnosis codes between December 31, 2013, and December 31, 2015, and following them to December 31, 2016. The setting included three local hospitals that were part of a larger hospital system in North Carolina, located in two counties. Patients 55 years and older who were admitted with ICD-9/10 diagnosis codes of 008.45 and A04.7 were included in the study; any patients who were hospitalized less than 24 hours were excluded. Recurrence of CDI within 1 year was documented. For purposes of this study, CDI recurrence was not classified as hospital-acquired or community-acquired. This study was approved by the institutional review board of the local university and hospital system.
Data Collection
The study used a retrospective data source that was extracted from the EHR by approved personnel at the hospital system and transferred into a consolidated database. The study period ranged from December 31, 2012, to December 31, 2016, to capture any prior hospitalizations that would indicate an initial CDI episode, and follow any CDI presentation for 1 year thereafter to capture any recurrence. Sociodemographic data, laboratory measurements, chronic diseases by ICD-9/10 codes, functional status/activities of daily living (ADLs), psychosocial data, demographic data, and PPI use were obtained via the electronic healthcare records. Dates were included to identify timing of laboratory results during the hospital stay. All laboratory data obtained were extracted from the first availability of markers on admission and the last recorded laboratory measures at discharge. No personal identifiers were included with each grouping of individual data.
Statistical Analysis
After the data were extracted, 1,598 patients presented during the time frame of the study period with 2,146 total admissions. These records were reviewed for inclusion and exclusion criteria, removing 372 patients younger than 55 years, nine patients with admissions less than 24 hours, and 346 patients presenting in 2016 without ability to be followed for 1 year, resulting in a final analysis sample of 1,199 admissions on 871 patients. Descriptive statistics such as frequency (n), percentage (%), mean (M), and standard deviation (SD) were used to describe the study patients. Bivariate analyses were performed by CDI recurrence status using t tests or Mann-Whitney U tests for continuous variables and [chi]2 or Fisher's exact tests for categorical variables. Multivariable logistic regressions were performed to further assess factors associated with CDI recurrence. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) estimated effects from logistic modeling. All analyses were performed in R statistical software v3.4.2 (R Core Team, 2017). A two-sided p-value < .05 was considered statistically significant.
Results
Among the 871 patients, the total number of admissions ranged from one presentation to 10, with 76.1% admitted only once (Table 1). A recurrence rate of 23.9% (n = 208) was noted for the study period. During the first admission, there were 79 deaths (9.1%), and the average age on initial admission for those expiring was 75.1 years (SD = 9.5). The majority of these deaths during the first admission were 65 years and older (n = 67, 84.8%), predominantly White (n = 56, 70.9%), and over half were female (n = 44, 55.7%).
The average age for the overall sample (n = 871) was 73.6 years (SD = 10.7) and predominantly White (n = 609, 69.9%) and female (n = 510, 58.6%). Prior to initial presentation, almost two-thirds (n = 576, 66.1%) resided in a private residence, followed by skilled nursing facility (n = 125, 14.4%). After initial admission, about one-third of the patients were discharged to either home/self-care (n = 279, 32.0%) or to a skilled nursing facility (n = 261, 30.0%). The index admission average length of stay was 8.8 days (SD = 8.6), and those with recurrent CDI had average lengths of stay at index admission of 8.9 days (SD = 8.3). The average number of days from first discharge to first recurrent admission was 71.2 (SD = 41.7), and 77.9% of patients with recurrence over the study period had greater than or equal to 30 days between discharge and recurrent admission (n = 159).
CDI recurrences were more prevalent if discharged to a skilled nursing facility (37.5% vs. 27.6% with no recurrence) or discharged home with the assistance of home health services (24.5% vs. 15.2% with no recurrence) (p < .001). Recurrent CDI was more prevalent (27.4% of those with recurrent CDI vs. 20.5% of no recurrence) in adults 55-64 years old (22% of the sample) relative to older adults 65 years and older (72.6% with recurrent CDI vs. 79.5% of no recurrence). This association also remained in multivariable logistic regression modeling, where patients 55-64 years old had 59.6% higher odds of recurrent CDI relative to those 65 years and older, adjusted for other sociodemographics (AOR [95% CI] = 1.596 [1.014, 2.491], p = .041) (see Table 2).
Chronic Diseases and Laboratory Abnormalities
The most common chronic diseases in the sample included hypertension (n = 703, 80.7%), arthritis (n = 384, 44.1%), cancer (n = 362, 41.6%), and diabetes (type 1 and type 2) (n = 356, 40.9%) (Table 3). Chronic diseases that were significantly more prevalent in patients with recurrent CDI included hypertension (88.0% vs. 78.4%; p = .003), heart failure (36.1% vs. 25.6%; p = .005), and chronic kidney disease (34.1% vs. 24.9%: p = .011). PPI use was not associated with recurrent CDI. No laboratory abnormalities were significantly associated with CDI, except alanine aminotransferase (ALT) at discharge when less than 17 or more than 30 U/L versus otherwise (Table 4). However, over half of the sample had documented hypoalbuminemia, elevated creatinine, leukocytosis, and elevated blood glucose greater than 120 mg/dl. For purposes of this study, polypharmacy was indicated in the EHR as seven medications or more on admission and was found in almost two-thirds of the sample (n = 569, 65.3%).
Smoking status was assessed at time of admission, with more than half of the sample having ever smoked (n = 515, 60.1%). Although not statistically significant, 63.9% (n = 133) of those with recurrent CDI had ever smoked relative to 57.8% (n = 383) without ever smoking. The average body mass index (BMI) at initial admission was 27.0 kg/m2 (SD = 7.5), with 26.9% of the sample (n = 199) having a BMI greater than 30 kg/m2 on initial admission. Recurrent and nonrecurrent groups had similar BMI ranges greater than 30 kg/m2, with 23.1% (n = 48) in the recurrent group and 22.8% (n = 151) in nonrecurrent group (p = .890).
Functional Status and ADLs
Over half of the sample had slightly limited mobility (n = 467, 57.4%) on initial admission, followed by very limited (n = 239, 29.4%) (see Table 5). For the recurrence group, about one-fifth of patients (n = 44, 21.2%) had very limited mobility compared with the nonrecurrent group (n = 195, 29.4%). Over half (n = 386, 51.1%) could independently perform ADLs on initial admission, without any significant difference (p = .836) between recurrent (n = 89, 42.8%) and nonrecurrent groups (n = 297, 44.8%).
The average Braden scale score (see Table 6 for criteria) on initial admission was 16.3 (SD = 3.1), whereas over two-thirds of the sample (n = 579, 71.1%) had a Braden scale score less than 18 on admission. However, there was no significant difference by recurrent CDI status (p = .948). Over half of the sample (n = 482, 59.1%) was classified as a high fall risk, 58.2% (n = 121) with recurrent CDI compared with 54.4% (n = 361) of nonrecurrent patients.
Psychosocial
Support systems for the sample were predominantly children (n = 452, 51.9%), followed by spouse/significant others (n = 340, 39.0%), other relatives (n = 173, 19.9%), and friends/neighbors (n = 128, 14.7%) (see Table 7). Similar support systems were noted with and without recurrence on initial admission. Physical, verbal, sexual abuse, and self-neglect were largely denied at initial admission, with no significant differences by recurrent CDI status.
Discussion
The average age on initial admission was similar to findings in other studies (Fernandez-Cotarelo et al., 2019; Milani et al., 2016; Van Esch et al., 2015; Venkat et al., 2016), with White females comprising over half of the overall sample, which is consistent with national trends for CDI (Kelly et al., 2021; Shrestha, Bime, & Taleban, 2018). In addition, predominantly White females are reflective of the local community population in counties where the hospital system resides. As of 2021, the United States Census Bureau (n.d.) reported over half of the local population served were female (ranging from 51.5% to 52.5%) and White (54.8% to 76.9%). The age group of 65 years and older ranged from 15.9% to 21.2% (United States Census Bureau, n.d.). CDI recurrence over the study period was 23.9%, which is consistent with estimate recurrence rates of 10%-40% after initial admission (Collins et al., 2015; Garey, Sethi, Yadav, & DuPont, 2008; Kelly & LaMont, 2008).
Age was found to be the only sociodemographic variable related to recurrent CDI admission. Recurrent CDI was more prevalent (27.4% of those with recurrent CDI vs. 20.5% of no recurrence) in the ages 55-64 years (22% of the sample) relative to patients 65 years and older in bivariate analysis (72.6% with recurrent CDI vs. 79.5% of no recurrence). Age was also an independent predictor for recurrent CDI after multivariable logistic regression when adjusting for other sociodemographics. These findings contrast with the literature, which supports an increased risk of recurrence with increasing age (Dumic et al., 2019; Louie et al., 2013). However, Collins et al. (2015) did not find increasing age related to CDI readmission in a sample of persons 65 years and older. Furthermore, Olsen, Stwalley, Demont, & Dubberke (2018) found that age alone did not predict the risk of CDI, because overall health conditions should be taken into consideration.
Interestingly, recurrence rate of hospital-acquired infections ranges from 5% to 50%, with a median of 20% (Mounsey, Lacy Smith, Reddy, & Nickolich, 2020). For this study, it is unknown whether CDI was hospital-acquired or community-acquired. The majority of the sample had recurrences 30 days or later between first discharge and subsequent recurrent admission. Although recurrent CDI usually happens within 2-8 weeks after antibiotic treatment, recurrence can occur months later (McDonald et al., 2018), as found in this current study.
CDI recurrence was more prevalent for those discharged to a skilled nursing facility and home with home healthcare services. A large cohort study also had similar findings, whereby those initially diagnosed in nursing facilities were at higher risk for recurrent CDI (Ma, Brensinger, Wu, & Lewis, 2017). However, home healthcare services were not examined in the larger cohort study (Ma et al., 2017). Collins et al. (2015) reported differing results that skilled nursing facilities, hospice, and long-term care decreased the odds of CDI readmission. Collins et al. (2015) hypothesized that ongoing care from outpatient facilities, hospital, and long-term care could contribute to compliance and potential ongoing treatment opportunities in those settings, which could in turn decrease readmission rates.
For this study, it is unclear why CDI recurrence was more prevalent for those discharged to skilled services or with home health; however, it is posited that these patients may have a larger comorbidity burden, chronic illnesses, and functional decline that would increase risk of recurrence. Further research is needed to explore these differing findings. The average length of stay for an index admission was 8.8 days, with an average length of stay at index admission for those with eventual recurrent CDI admission of 8.9 days; this is higher than a recent national estimate of 5.8 days for CDI admission (Shrestha et al., 2018).
Those with recurrent CDI in this study were found to have greater prevalence of hypertension, heart failure, and kidney disease, supporting other research, which found higher proportions of patients with chronic kidney disease and congestive heart failure during recurrent episodes, along with diabetes and chronic obstructive pulmonary disease (Kichloo et al., 2022). Ma et al. (2017) also found that chronic kidney disease was associated with increased risk of recurrent CDI, yet diabetes and inflammatory bowel disease were not associated with recurrent CDI in their study. Our study did not find diabetes as significant for recurrent CDI despite prevalence in the sample.
Although no laboratory abnormalities were significantly associated with recurrent CDI, over half the sample presented with hypoalbuminemia, elevated creatinine, leukocytosis, elevated blood glucose greater than 120 mg/dl, and polypharmacy with almost two-thirds of the sample taking seven or more medications on initial admission. These findings are consistent with known risk factors for severe CDI presentation to include, but are not limited to existing chronic kidney disease, hyperglycemia, hypoalbuminemia, and leukocytosis (Olsen et al., 2018). Chronic kidney disease and end-stage renal disease are associated with increased risk of recurrence (McDonald et al., 2018). Elevated white blood cell count greater than 15 g/dl and creatinine 1.5 mg/dl or greater are consistent with severe presentation of CDI (Johnson et al., 2021). Blood urea nitrogen (BUN) and creatinine were elevated in approximately half the sample, which is likely multifactorial in the setting of acute diarrheal illness, and this improved through hospitalization. Close attention to laboratory markers during admission is vital to the care of the whole patient, as hypoalbuminemia and elevated creatinine are risk factors for 30-day mortality in older adults with CDI (Leibovici-Weissman et al., 2017).
PPI use has been associated with CDI and recurrence, but literature remains mixed regarding findings (Freedberg, Salmasian, Friedman, & Abrams, 2013; Govoni, Zurlo, De Giorgio, Cultrera, & Volpato, 2021; Ma et al., 2017; Trifan et al., 2017). More recently, Govoni et al. (2021) did not find a significant relationship with PPI use and CDI recurrence, whereas Ma et al. (2017) found an increased risk for recurrent CDI with PPI use. In this current study, PPI use was not associated with recurrent CDI; however, judicious use is appropriate if PPI therapy is indicated per current guidelines (Kelly et al., 2021).
Approximately two-thirds of the sample had a Braden scale score of less than 18, raising concern for pressure ulcer risk (Braden & Bergstrom, 1994), and over half of the sample was at high fall risk. In fact, 20.0% of the sample had fallen within the past 6 months at time of the first admission. Functional impairment and disabilities were found prevalent in CDI admissions in a recent retrospective study (Govoni et al., 2021). Another retrospective study, however, found higher baseline functional deficits in CDI cases when compared with non-CDI, an increase in delirium compared with controls, and significantly higher mortality rate for patients with dementia compared with those without dementia (Fernandez-Cotarelo et al., 2019). Functional status and ADLs should be taken into account during admission for CDI, as the functional status may worsen and lead to poorer outcomes.
Limitations
Several limitations must be noted for this study. Due to a retrospective approach, chart documentation was not always complete or consistent on each individual. Also, patients who expired after index admission prior to a recurrence of CDI were excluded from further analyses for recurrence. Initial admission was verified by reviewing data from the previous year to capture an index admission, but patients could have had a prior event unknown due to date ranges. For this reason, the study period allowed admission reviews to determine presentation.
Documentation in the EHR may not be fully completed by clinical staff and providers. Admitting diagnosis was not known, and antibiotic exposure prior to initial and recurrent admissions was unknown for this study. Timing of CDI diagnosis during admission is unknown, thereby limiting ability to define healthcare-acquired versus community-acquired. CDI severity was not determined, nor was level of care and antibiotic treatment regimen during hospitalization and at discharge. Although discharge disposition was captured for the sample, events after discharge including compliance, appropriate sanitization of homes and facilities, presentations to other nonparticipating hospital systems, support systems at home, and even death were unable to be known.
Discharge locations for individuals may not have been the same as preadmission, as prevalence of recurrent CDI was greater in those discharged to a skilled nursing facility or home with home healthcare services after initial admission. It is unknown the extent of home health services or why home health may have been required, which remains a limitation due to the retrospective nature. Hospital-acquired versus community-acquired CDI are unknown from this study. Finally, comorbidities extracted may not be completely exhaustive.
Implications for Practice
Findings from this study revealed laboratory abnormalities and comorbidities that may be addressed during acute hospitalizations were specifically found and populated in the EHR during hospitalization routinely. A large portion displayed hypoalbuminemia, leukocytosis, and abnormal renal function, which is found with severe CDI presentation (Kelly et al., 2021; Olsen et al., 2018). Care should be taken to address nutritional status, as hypoalbuminemia is associated with development of frailty and mortality and more severe and progressing CDI (Ahmed, Crawford, Arora, & Maskey, 2021; Fontana et al., 2013). Although in the setting of acute diarrheal illness, BUN and creatinine may be elevated due to dehydration, close attention to these markers while hospitalized can help decrease mortality, as both are risk factors for 30-day mortality in the older adult with CDI (Leibovici-Wessman et al., 2017).
Review of comorbidities in the older adult is essential, as CDI recurrence is most likely with underlying severe comorbidities (Dumic et al., 2019). As seen in this study, age was the only sociodemographic variable related to recurrent CDI admission, with recurrence more prevalent in ages 55-64 years in bivariate analysis. Age was also an independent predictor for recurrence after multivariable logistic regression when adjusting for other sociodemographics, raising awareness that age alone does not explain recurrent CDI. Additional factors such as comorbidities, underlying health conditions, functional status, and frailty should be assessed and intervened as appropriate to reduce risk of adverse outcomes.
Although inpatient, chronic disease should be managed to avoid compounding CDI impact. Care should be taken to ensure assessment and recognition of known comorbidities that contribute to morbidity, mortality, and recurrence. Declining functional status is known as an independent risk factor for adverse outcomes in older adults, including severity of CDI and prolonged illness (Fernandez-Cotarelo et al., 2019). Including the multidisciplinary team will ensure the patient's treatments of known underlying conditions are optimized while inpatient. Additional assistance from the multidisciplinary team such as physical therapy, occupational therapy, and nutritionists is vital. A proposed CDI admission assessment is outlined in Table 8 to guide nurses and other providers at time of hospitalization.
Nurses in the inpatient setting have a prime opportunity to encourage mobility measures, frequent turning, serial assessments, and detailed documentation. Pharmacy consultation may be beneficial to decrease polypharmacy and assist with streamlining medications while inpatient and upon discharge. PPI use may be continued in patients with CDI if benefits outweigh risks and there is an appropriate indication for PPI therapy (Kelly et al., 2021). Probiotic therapy is not indicated, as insufficient data exist to support its use (McDonald et al., 2018). Close follow-up with primary care providers and specialists is vital for continuity of care.
Proper sanitization of living arrangements should be reviewed with patients and family members when returning home, as spores survive even in harsh environments. These spores can be found on surfaces including food, animals, and any surfaces that individuals touch daily (Orenstein & Patron, 2019). While inpatient, patients should be in private rooms, with contact precautions in place. Dedicated equipment such as stethoscopes should be assigned to the patient's room to avoid spreading to others. At times, private rooms may not be available; in this case, patients should be grouped together according to the infecting organism (McDonald et al., 2018). Contact precautions should start immediately at first suspicion of CDI and continue for at least 48 hours after diarrhea has resolved (Johnson et al., 2021; McDonald et al., 2018; Mounsey et al., 2020).
Transportation of individuals from a hospital to other facilities via transport or emergency medical services should continue contact precautions to decrease risk of CDI transmission. Cleaning of rooms and reusable equipment should be performed with a United States Environmental Protection Agency-approved sporicidal bleach disinfection (McDonald et al., 2018). As an outpatient, family and patients should ensure all surfaces are cleaned with bleach, employ hand washing with soap and water, and provide a dedicated bathroom if possible.
Close follow-up should be arranged for patients, as recurrence is most likely to occur during the first month following treatment in the setting of disrupted colonic flora (McDonald et al., 2018). Individuals with risk factors for recurrence should be followed closely, with therapeutic response based on clinical signs and symptoms; no repeat diagnostic testing is necessary to ensure resolution (McDonald et al., 2018). A proposed discharge planning toolkit is also included in Table 9 to help guide seamless discharge for patients hospitalized with CDI.
Conclusions
Utilizing routinely captured EHR data during an acute hospitalization will aid in targeting care for this vulnerable population, in the hopes of reducing morbidity, mortality, and recurrence. By assessing laboratory measures, comorbidities, functional status, and support systems, targeted interventions can be developed for the patient. Inclusion of the multidisciplinary team is vital for promoting best outcomes and decreased risks of recurrence and mortality.
References