Clostridium Difficile Research Articles

Comparison of Medicare Claims-based Clostridioides difficile infection classification to chart review using a linked cohort

Background: Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. Categorizing CDI based on location of onset and potential exposure is critical in understanding transmission patterns and prevention strategies. While claims data are well-suited for identifying prior healthcare utilization exposures, they lack specimen collection and diagnosis dates to assign likely location of onset. Algorithms to classify CDI onset and healthcare association using claims data have been published, but the degree of misclassification is unknown. Methods: We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016-2020 to Medicare beneficiaries using residence, birth date, sex, and hospitalization and/or healthcare exposure dates. Uniquely linked patients with fee-for-service Medicare A/B coverage and complete EIP case report forms were included. Patients with a claims CDI diagnosis code within ±28 days of a positive CDI test reported to EIP were categorized as hospital-onset (HO), long-term care facility onset (LTCFO), or community-onset (CO, either healthcare facility-associated [COHCFA] or community-associated [CA]) using a previously published algorithm based on claim type, ICD-10-CM code position, and duration of hospitalization (if applicable). EIP classifies CDI into these categories using positive specimen collection date and other information from chart review (e.g. admit/discharge dates). We assessed concordance of EIP and claims case classifications using Cohen’s kappa. Results: Of 10,002 eligible EIP-identified CDI cases, 7,064 were linked to a unique beneficiary; 3,451 met Medicare A/B fee-for-service coverage inclusion criteria. Of these, 650 (19%) did not have a claims diagnosis code ±28 days of the EIP specimen collection date (Table); 48% (313/650) of those without a claims diagnosis code were categorized by EIP as CA CDI. Among those with a CDI diagnosis code, concurrence of claims-based and EIP CDI classification was 68% (κ=0.56). Concurrence was highest for HO and lowest for COHCFA CDI. A substantial number of EIP-classified CO CDIs (30%, Figure) were misclassified as HO using the claims-based algorithm; half of these had a primary ICD-10 diagnosis code of sepsis (226/454; 50%). Conclusions: Evidence of CDI in claims data was found for 81% of EIP-reported CDI cases. Medicare classification algorithms concurred with the EIP classification in 68% of cases. Discordance was most common for community-onset CDI patients, many of whom were hospitalized with a primary diagnosis of sepsis. Misclassification of CO-CDI as HO may bias findings of claims-based CDI studies.

Age related Antibiotic Prescribing Trends of Clostridioides Difficile Incident Cases within Davidson County TN 2012-2020

Age related Antibiotic Prescribing Trends of Clostridioides Difficile Incident Cases within Davidson County Tennessee 2012-2020 Michael Norris, MSN, Priscilla Pineda, MPH, Malakai Miller, MPH, Raquel Villegas, PhD, MS Background: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the United States. Antibiotic use is considered a predisposing factor for CDI. The State of Tennessee collaborates with the CDC as part of an ongoing Emerging Infections Program (EIP). We sought to better understand the impact of antimicrobial use prior to the date of incident of CDI within the defined age groups of Davidson County, Tennessee. Methods: Surveillance data from the years 2012–2020 were examined for all positive CDI cases within Davidson County. A positive CDI case was defined as a laboratory confirmed case who is ≥ 1 year old living in Davidson County, Tennessee. Antibiotic use was assessed in the 12 weeks prior to CDI. Trends of overall antibiotic use, including the top five antibiotics prescribed by our defined age groups were examined. Analyses were performed using SAS version 9.4. Only fully abstracted cases are included in the study. Results: Among 7,346 positive CDI incident cases identified between 2012–2020, 5,467 (74.4%) received antibiotics 12 weeks prior to a confirmed infection. We looked at the trend of antibiotic prescription over time from 2012-2020 (77.0%, 76.7%, 74.3%, 80.7%, 76.3%, 75.1%, 73.7%, 74.8% and 71.5%) which has decreased since 2015. The prevalence of antibiotic use by age group 1-18 years, 19-44 years, 45-64 years, 65-74 years, and 75+ years was 53.4%, 68.8%, 74.5%, 79.2% and 83.1% respectively. The five most prescribed antibiotics were ceftriaxone ((11.1%), followed by vancomycin IV (10.9%), ciprofloxacin (10.2%), metronidazole (9.1%), and piperacillin (8.6%). Cases in the 45-64 years age group were more likely to be prescribed vancomycin IV, ciprofloxacin, metronidazole, and piperacillin-tazobactam compared to other age groups (p < 0.0001). There was no statistically significant association between ceftriaxone prescription and our defined age groups. Conclusion: In this study, almost three quarters of the CDI cases had received antimicrobial therapy in the 12 weeks prior to infection. Since antibiotic prescription is a potentially modifiable risk factor for CDI, a more in-depth study, combined with an antibiotic stewardship program implementation in all settings would be beneficial to reduce the risk of CDI complications of antibiotic usage.

Underlying Conditions in Community-associated Clostridioides difficile Infections in Davidson County, Tennessee

Background: Clostridioides difficile infections (CDI) are a crucial public health threat becoming a worldwide problem. In 2017, there were 223,900 incident cases and 12,800 deaths in the United States. Underlying conditions, such as diabetes mellitus (DM), put individuals at a greater risk for developing an infection. Whereas CDI was once believed to be mostly healthcare-associated, increasing evidence points to transmission in community settings (CA). We investigated characteristics of CA CDI and associations between pre-existing conditions and CA incident CDI cases using data from Tennessee’s CDI surveillance program, an active population- and laboratory-based surveillance system conducted through CDC’s Emerging Infections Program. CA incident CDI case data were downloaded from the Incident Case Management System from 2017 to 2021. Count and percentages were determined for each underlying condition, number of underlying conditions, and biological sex. Chi-square analyses determined associations between underlying conditions and sex. Statistical analyses were conducted using SAS v9.4. 2,326 CA incident CDI cases were identified from the catchment area. The case rates per 100,000 population between 2017 and 2021 were 79.7, 81.9, 73.7, 50.7, and 49.6. A total of 39% of the cases were 65 years or older. Most cases were women (64.8%). The overall prevalence for any underlying condition among CA CDI cases was 67.4%. A total of 29.4% of incident cases had one condition, 18.5% had two conditions, and 19.4% had three or more conditions. The most frequently reported pre-existing conditions was DM (22.9%) and gastrointestinal disease (21.7%). We looked at the prevalence of underlying conditions separated in men and women. Men with CA CDI were more likely to have chronic kidney disease (CKD) (19.1% vs 12.7%), DM (26.0% vs 21.2%), immunocompromised conditions (6.4% vs 3.6%), liver diseases (6.5% vs 2.8%), and plegias (1.0% vs 0.2%) than women with CA CDI. Women with CA CDI were more likely to have chronic lung diseases (17.4% vs 12.6%) and connective tissue diseases (4.9% vs 2.2%) than men with CA CDI. Although the incident CA CDI case rate in Davidson County decreased from 2018 to 2021, it remains a significant threat. In this analysis, underlying conditions in persons with CA CDI were highly prevalent. Men were more likely to have underlying conditions in general, and specifically CKD and DM, than women. Improving understanding of the prevalence of these conditions with CA CDI cases, along with their antibiotic use and community exposures, can help drive prevention strategies to mitigate CA CDI transmission.

Infections in residents of long- term care facilities in southern Poland, 12-month surveillance preliminary results

Long-Term Care Facility (LTCF) residents are particularly vulnerable to infections due to factors such as advanced age, co-morbidities, and regular medication use. Data from American and European sources indicate an anticipated occurrence rate of 2 to 11 infections per 1000 patient-days (pds) in LTCFs. The incidence rate of Clostridioides difficile infections (CDI) is reported at 0.52 per 10,000 resident days. The research objectives aimed to assess infection epidemiology in Polish LTCFs. An observational prospective study was conducted on residents from five LTCFs (2 residential homes and 3 nursing homes) in southern Poland between September 2022 and September 2023, utilizing the definition from the pan-European HALT study. The study received approval from the Bioethics Committee of the JU (1072.6120.73.2022) and was funded by the Polish NCN grant No.2021/41/B/NZ6/00749. CDI was defined by positive toxins A and B enzyme immunoassays (EIA) and positive glutamate dehydrogenase (DHA) EIA. Results from the study, involving 250 residents, revealed 157 cases of Healthcare-Associated Infections (HAIs) excluding gastrointestinal and CDI, with an incidence rate of 1.97/1000 pds. Lower respiratory tract infections dominated with 77 cases, including 36 pneumonia cases (47%). Additionally, 25 cases of gastrointestinal infections were reported, including only 7 CDI cases, resulting in an incidence rate of 0.88 CDI per 10,000 pds. Norovirus was detected in only one case, while the microbiological results were negative in the remaining cases. The incidence rate among Polish LTCF residents was lower than expected, contrasting with the CDI incidence that aligned with other research findings. Notably, the etiology of diarrhea remained undetermined in 68% of cases.

Need for improvement in the care of patients with Clostridioides difficile infections (CDI) - expert opinion in international comparison

Clostridioides difficile infection (CDI), as a nosocomial disease, is associated with high morbidity and mortality. Even though the incidence of CDI has been declining in Germany in recent years, the individual infection may pose a medical challenge despite therapeutic advances. The aim here is to clarify which gaps practitioners consider to be particularly serious in care and in the existing evidence base. In a moderated workshop of German CDI experts the topics considered as relevant were identified. A survey already conducted in five other countries (Australia, France, Great Britain, Canada, and Italy) was adapted and processed by 27 practitioners. During the evaluation, the topics perceived as particularly important were identified, the statements of the specialist groups were compared and changes in opinion were considered. 27 fully completed questionnaires were evaluated. The need for improvement was primarily seen in the prevention of CDI recurrences (74.1%) and the treatment of recurrences (55.6%). Evidence deficits were noted in the treatment of recurrences (55.6%) and identification of risk factors for recurrences (48.1%). Improving care via fecal microbiota transfer (FMT) was named by 70.4%. For guidelines, more clarity (48.1%) and more regular updates (40.7%) were desired. For patients, better education on appropriate antibiotic use (52.0%) and choice of FMT were desired (48.1%). The German expert view and the international assessment is similar, when asked about the need for improvement in care and evidence gaps in the treatment of patients with CDI: The focus is on prevention and therapy of recurrent CDI. The problem of access to FMT is a German peculiarity that seems to need improvement.

Impact of Clostridioides difficile Reporting on Antimicrobial Therapy Days Directed at Treatment of C. difficile Infections

Background: Previous studies have found that solely relying on molecular testing is likely to result in the overdiagnosis and overtreatment of C. difficile infections (CDI). Comparable outcomes have been demonstrated in patients with a positive molecular test (C. difficile PCR) result and a negative toxin immunoassay (C. difficile toxin) compared to patients without CDI by either testing Method: In 2021 Memorial Hermann Healthcare System converted from C. difficile PCR testing only to C. difficile PCR testing with reflex to C. difficile toxin if positive. A previous internal audit revealed that despite this change in testing, patients who were C. difficile PCR positive and C. difficile toxin negative were still receiving treatment. This study aimed to evaluate the impact of C. difficile reporting on the total days of therapy directed at the treatment of CDI of an 11-hospital health care system in patients who testing C. difficile PCR positive/C. difficile toxin negative. Methods: Pre-post, multicenter, retrospective, observational study conducted from January 1, 2023 through March 31, 2023 (pre-intervention) and July 1, 2023 through September 31, 2023 (post-intervention) which included hospitalized adult patients with a C. difficile test ordered within the study period. Intervention included a change in reporting of C. difficile PCR positive/C. difficile toxin negative results to display a laboratory comment. The comment notifies providers of the positive C. difficile PCR result while highlighting this probably reflects colonization with C. difficile as the C. difficile toxin is negative and treatment is rarely indicated. Results: In total, 989 C. difficile PCR were order in the pre-intervention cohort compared to 1009 in post-intervention. The overall rate of patients that received therapy directed at CDI decreased from 14% to 10% after the implementation of reporting change. Total days of therapy (DOT) also decreased by 29% from 482 to 342. Days of therapy that were administered to patients with C. difficile PCR positive/negative C. difficile toxin test decreased from 183 to 91. Conclusions: Adjusting the reporting of C. difficile results led to an overall numerical decrease of antimicrobial DOT directed at CDI treatment. In particular, among patients with a positive C. difficile PCR/C. difficile toxin negative test a 50% reduction in DOT was observed. Further data are required to assess the overall clinical impact of adjusting CDI reporting methods.

Molecular and Epidemiological Characterization of Pediatric and Adult C. difficile Infection in Canadian Hospitals, 2015-2022

Background: The molecular and epidemiological landscape of C. difficile infection (CDI) has evolved markedly in the last decade; however, limited information is available contrasting differences between adult and pediatric populations. We describe a multicenter study evaluating healthcare-associated (HA) and community-associated (CA) adult and pediatric-CDI identified in the Canadian Nosocomial Infection Surveillance Program (CNISP) network from 2015 to 2022. Methods: Hospitalized patients with CDI were identified from up to 84 hospitals between 2015–2022 using standardized case definitions. Cases were confirmed by PCR, cultured, and further characterized using ribotyping and E-test. We used two-tailed tests for significance (p≤0.05). Results: Of 30,817 cases reported, 29,245 were adult cases [HA-CDI (73.2%), CA-CDI (26.8%)] and 1,572 were pediatric cases [HA-CDI (77.7%), CA-CDI (22.3%)]. From 2015 to 2022, HA-CDI rates decreased 19.7% (p=0.007) and 29.4% (p=0.004) in adult and pediatric populations, respectively (Figure 1). CA-CDI rates remained relatively stable in the adult population (p=0.797), while decreasing 60.7% in the pediatric population (p=0.013). Median ages of adult and pediatric patients were 70 (interquartile range (IQR), 58–80) and seven (IQR, 3–13) years, respectively. Thirty-day all-cause mortality was significantly higher among adult vs. Pediatric CDI patients (11.0% vs 1.4%, p < 0.0001). No significant differences in other severe outcomes were found. Ribotyping and susceptibility data were available for 4,620 samples: 3,558 adult (77.0%) and 1,062 pediatric (23.0%). The predominant adult and pediatric ribotypes (RT) were 106 (12.2/16.2%), 027 (11.4/3.2%), and 014 (8.8/8.2%). Overall, RT027 prevalence significantly decreased from 17.9% in 2015 to 3.2% in 2022 (p=0.003), while RT106 increased from 8.5% to 14.4%. Resistance rates among adult and pediatric isolates were similar for all antimicrobials tested except moxifloxacin (16.2% vs. 6.2%, p < 0.0001, respectively). Adult moxifloxacin resistance decreased from 30% to 6.3% from 2015 to 2022 (p=0.006). Adults with moxifloxacin-resistant CDI were older (median: 74 vs. 69 years, p < 0.001) and had higher thirty-day all-cause mortality (13% vs. 9.8%, p=0.041) and recurrence (10% vs. 5.7%, p < 0.001) compared to those with moxifloxacin non-resistant CDI, while these trends were not observed in pediatric patients. Among RT027 strains, moxifloxacin resistance decreased from 91.0% in 2015 to 7.1% in 2022. There was one metronidazole-resistant pediatric sample in 2018 and no resistance to vancomycin or tigecycline in either population. Conclusion: We have found differences in the epidemiological and molecular characteristics of adult and pediatric CDI, with higher thirty-day all-cause mortality among adults. Overall, RT106 has replaced RT027 as the predominant ribotype with a concomitant decrease in fluoroquinolone resistance.

High Prevalence of Laxative Use Among Those Tested for Clostridioides difficile Infection in VA Hospitals

Background: Clostridioides difficile infection (CDI) is associated with 500,000 infections and 30,000 deaths per year. Inappropriate testing and treatment of patients with asymptomatic colonization occurs frequently (between 15% and 41%). The VA CDI guidelines emphasize avoidance of CDI testing in patients with laxative use within the previous 48 hours due to the high likelihood of non-infectious diarrhea. The objective of this study was to assess laxative administration among inpatients tested for CDI in VA hospitals and identify factors associated with guideline discordance. Methods: Adults hospitalized in Illinois, Wisconsin, and Michigan VA Medical Centers from January 2019-December 2022 with a CDI test performed during the admission were included. CDI tests included Toxin B gene Polymerase Chain Reaction or Toxin Enzyme Immunoassay. Tests were defined as positive, negative, or cancelled according to the diagnostic protocols of the VA testing laboratories. Laxative use, patient demographics, admission data, and comorbidities were collected from the VA Corporate Data Warehouse. Guideline discordant testing was defined as a diagnostic test for CDI ordered within 48 hours of a recorded laxative dose. Factors associated with discordant testing were analyzed using clustered binomial logistic regression models. Analyses were completed using SAS 9.4. Results: There were 7,326 tests ordered for 4,888 patients during the study. Patients were predominantly White (61.8%), male (95.6%), and elderly (mean age=70.0 standard deviation=12.1). Most (59.0%) patients had received at least one dose of laxative in the 48 hours preceding their CDI test. Being Black (Odds Ratio (OR)=0.86 (95%Confidence Interval (95%CI) =0.76,0.98) or Hispanic (OR (95%CI) =0.62(0.48,0.82) vs White) was associated with a decreased likelihood of inappropriate testing due to recent laxative use. Being tested at a rural facility (OR (95%CI) =1.23 (1.07,1.41) vs urban), within a long-term care (LTC) unit (OR (95%CI) =1.67 (1.41,1.97) vs inpatient), or within an intensive care unit (ICU) (OR (95%CI) =1.40 (1.24,1.59)) were all associated with an increased likelihood of being inappropriately tested. Guideline discordant tests were more likely to have negative results (OR (95%CI) =1.25 (1.05,1.49)) compared to guideline concordant tests. Discussion: Laxative administration in the 48 hours preceding CDI testing was common among hospitalized Veterans and associated with a lower likelihood of positive Results: This echoes non-VA studies where laxative use was reported at 44%. An increased likelihood of guideline discordant testing in ICU and LTC settings suggests the need for greater diagnostic stewardship interventions. Additionally, further work to determine negative outcomes associated with inappropriate testing are needed.

Clinical Characteristics and Cycle Thresholds Among Discordant and True Positive Test Results for Clostridiodes difficile

Background: The diagnosis of Clostridioides difficile infection (CDI) is challenging. Despite guideline-directed, multistep testing algorithms and diagnostic stewardship, the treatment of C. difficile colonization persists. The testing algorithm at our system utilizes an initial real-time PCR test (PCR) for Toxin B gene, which if positive, reflexes to an enzyme immunoassay (EIA) for detecting Toxins A and B. Discordant results (PCR +/EIA -) are suggestive of colonization, but the majority of patients with discordant results are treated for CDI. Correlation of C. difficile EIA B polymerase chain reaction (PCR) cycle thresholds (Ct) with the presence of free EIA and disease severity has been observed, but the ability to use Ct in the decision to treat patients with discordant results is unclear. Our study assesses if Ct values and other clinical characteristics favor treatment in select patients with discordant Methods: A retrospective chart review was performed of adult patients (≥ 18-year-old) with positive C. difficile PCR results that were admitted to our health system between June 01 and August 31, 2023. C. difficile PCR and Ct results were obtained by Cepheid GeneXpert and Toxin A and B EIA results were obtained by Meridian Bioscience Immunocard. Patients with discordant (PCR+/EIA) and true positive (PCR+/EIA+) results were compared. We assessed demographics, past medical history, clinical characteristics, severity of illness, PCR Ct values, treatment, and clinical outcomes including: 30-day all-cause mortality and re-admission, and 60-day CDI repeat testing and treatment. Results Of the 122 patients identified, 89 patients had discordant results and 43 had true positive Results: Severity of illness and other clinical and laboratory characteristics were similar between both groups. Mean Ct values were significantly lower for true positive results compared to discordant results, 24.28 vs 29.27, respectively (p26 (p=.08). Of the patients with discordant results, 73 completed treatment for CDI and no difference in clinical outcomes was observed compared to patients with discordant results that were not treated. Conclusion Ct values were lower among patients with true positive results compared to patients with discordant Conclusion: There were no statistically significant different rates of severe or fulminant CDI among patients with discordant results and Ct values < 26, although this finding may be limited by sample size and Ct may be helpful in deciding which discordant patients to treat.

Longitudinal Follow Up of Patients Colonized with Clostridioides difficile: a Retrospective Cohort Study

Background: Patients colonized with Clostridioides difficile are at risk of transmitting C. difficile to other patients, and of developing C. difficile infection (CDI). Known risk factors for carriage include previous hospitalization, gastric acid suppression and previous CDI. Data regarding duration of carriage and its predictors are lacking but could be useful to better understand the natural evolution of carriage and better estimate the likelihood of transmission or progression to CDI. Methods: We performed a retrospective cohort study of C. difficile colonized patients with > = 1 admission to a tertiary academic institution between November 2013 and January 2017. Colonization status was determined upon hospital admission by detection of TcdB gene by polymerase chain reaction on a rectal screening swab, as part of a systematic screening program. Overall duration of carriage and predictors of prolonged carriage were explored using Kaplan-Meier methods and Cox regression. Results: There were 134 patients, who after having a positive initial screening test (and therefore identified as colonized with C. difficile), had subsequent testing. The median age was 77 years (IQR, 66 to 85), and 53.6% of the patients were female. After hospital discharge, 26 (19.4%) colonized patients progressed to CDI. Mean duration of follow up was 269 days, with a median of 179 days. Median duration of carriage was 211 days, (95% confidence interval (CI) [157, 264]). Predictors associated with decreased duration of C. difficile colonization included younger age (HR per unit decrease (year), 1.013; 95% CI, 1.025 to 1.001; p=0.03), and receipt of antibiotics in the 3 months prior to first admission (mean days to clearance of patients with and without recent antibiotic use, 252 days vs 372 days, respectively; HR, 1.55; 95% CI, 1.01 to 2.36; p < 0 .04). By contrast, the presence of comorbidities (e.g. heart failure, diabetes, cancer, and chronic kidney disease), the use of proton-pump inhibitors (PPIs), the receipt of antibiotics during the first admission, and the duration of first hospitalization were not associated with significant differences in duration of carriage. Conclusion: This study is the largest cohort of C. difficile carriers with longitudinal follow up of their colonization status. It highlights the extended duration of carrier status especially in older patients and identifies predictors of prolonged carriage. Further studies are needed to understand the underlying relationship with the predictors identified in this study.

Evaluation of Empiric Antibacterial Treatment and Subsequent De-escalation for Febrile Neutropenia

Background: Febrile neutropenia (FN) is the most common complication of chemotherapy-induced neutropenia that affects over 80% of patients with hematologic malignancies. National guidance and randomized controlled trial data demonstrate empiric antimicrobial therapy (EAT) can be discontinued after 72 hours of apyrexia and clinical recovery regardless of absolute neutrophil count (ANC). A 2019 internal study identified opportunity for improvement for targeted de-escalation. We aimed to reevaluate duration of EAT in patients with FN without a documented source of infection. Methods: A pharmacovigilance platform identified 110 patients from January to September 2023 without identified source of infection. Data collection was performed via manual chart review. Historic patient data from our 2019 cohort (n=50) was available in our research repository. The primary outcome was the duration of EAT in patients with at least 72 hours of apyrexia and clinical recovery, defined as normalization of vital signs. Secondary outcomes included adverse events associated with EAT, and initiation of intravenous vancomycin. Results: Baseline characteristics for 2023 were similar to historic, median age was 67.5 years, 56% were male, and median ANC at fever onset was 150 cells/μL. EAT was continued in 29 patients (58%) despite defervescence and stabilization versus 35 (70%) in 2019 (figure 1). Average duration (LOT) of EAT beyond clinical stabilization was 6 versus 7 days. Adverse effects due to EAT occurred in 13 patients in 2023 (26%) versus 4 (8%); of which, C. difficile infection (CDI) was the greatest contributor. Vancomycin was initiated in 31 patients (62%), 22 having no identifiable indication. Conclusions: Rates of EAT de-escalation for neutropenic patients after 72 hours of apyrexia and clinical stability improved by 12% as compared to 2019. Mean days of overall EAT was 3 days less in 2023. With a notable increase in CDI rates in 2023, dedicated time for antimicrobial stewardship review, clinician education and guideline driven alerts for review will be explored to help further improve practice.

The state of play of rodent models for the study of Clostridioides difficile infection.

Clostridioides difficile is the most common cause of nosocomial antibiotic-associated diarrhoea and is responsible for a spectrum of diseases characterized by high levels of recurrence and morbidity. In some cases, complications can lead to death. Currently, several types of animal models have been developed to study various aspects of C. difficile infection (CDI), such as colonization, virulence, transmission and recurrence. These models have also been used to test the role of environmental conditions, such as diet, age and microbiome that modulate infection outcome, and to evaluate several therapeutic strategies. Different rodent models have been used successfully, such as the hamster model and the gnotobiotic and conventional mouse models. These models can be applied to study either the initial CDI infectious process or recurrences. The applications of existing rodent models and their advantages and disadvantages are discussed here.

Leveraging the Electronic Medical Record in C. difficile Diagnostic Stewardship

Background: Clostridioides difficile PCR is extremely sensitive but cannot differentiate colonization versus active disease. Over diagnosis of C. difficile infection (CDI) has negative consequences including overuse of antibiotics targeting C. difficile, increased hospital-acquired (HA)-CDI rates, and increased healthcare costs. We describe the implementation of a Clinical Decision Support tool embedded in the C. difficile order and the result on testing, HA-CDI rates and healthcare costs. Methods: The C. difficile order was updated in June 2023 with 4 dynamic questions that reflex if specific criteria are identified in the electronic medical record in the prior 24 hours: less than 3 loose stools documented, receipt of laxative, opioid antagonist, oral contrast, or tube feed initiation. If any criteria are identified, an embedded alert triggers and the provider must choose “yes, high clinical suspicion” or “no (exit and cancel order)” in addition to providing an order indication. All inpatient C. difficile tests were reviewed from July 1 to Sept 30, 2022 (pre-update) and July 1 to Sept 30, 2023 (post-update). An order rate was calculated per 10,000 patient days as well as HA-CDI rate. Cost analysis was completed using direct lab costs and published costs of $35,000 per HA-CDI. Results of the order questions were reviewed post-update. Incident rate comparison was completed using medcalc. Results: Pre-update, 1147 tests were conducted, with an order rate of 104.3. Post-update, 919 tests were performed, with an order rate of 86.6. The positivity rate was 16.1% pre-update and 14.7% post-update. The incidence rate difference was 0.00177 (P 15 (145, 16%). 166 (18%) patients who received laxatives (18 positive, positivity rate 11%) were still tested. Conclusion: Implementation of a dynamic order led to a significant reduction in the total number of C. difficile PCR tests performed with associated reduction in HA-CDI and cost savings. Despite this, patients receiving laxatives were still being tested for C. difficile, highlighting the need for ongoing education and feedback. These results support the use of dynamic ordering for diagnostic stewardship, which can benefit both patients and hospitals.

PMN-MDSC: A Culprit Behind Immunosenescence and Increased Susceptibility to Clostridioides difficile Infection During Aging

Susceptibility to pathogens in the elderly is heightened with age, largely because of immunosenescence. As an immune regulatory organ, bone marrow creates immune cells that move to other organs and tissues through the blood. Despite the significance of this process of this organ, there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence. In this study, the compositions of immune cells in bone marrow from young (three months) and old (24+ months) mice were compared by means of mass cytometry, with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry. The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridioides difficile (C. difficile) infection model. Our results showed that aged mice presented with a reduction in bone trabeculae structure, which was accompanied by a notable increase in polymorphonuclear (PMN)-myeloid-derived suppressor cell (MDSC) abundance. Through bulk-seq and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis, we identified differential genes associated with the immune response—specifically, the Th17 cell differentiation pathway. Furthermore, the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C. difficile infection. After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody, the symptoms induced by C. difficile were significantly relieved, as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability. In conclusion, aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine, which contributes to susceptibility to C. difficile infection. This study provides a novel target for anti-aging therapy for immunosenescence, which is beneficial for improving immune function in elders.

Resetting the environmental reservoir; evaluating the impact of a new hospital building on Clostridioides difficile infection

Background: Prior research has implicated contaminated surfaces in the transmission of Clostridioides difficile within the hospital. To reduce the risk of transmission, enhanced environmental hygiene is performed in rooms of patients with known C.difficile infection (CDI). We wished to evaluate the residual impact of environmental surfaces on hospital-onset CDI (HO-CDI) by comparing HO-CDI rates before and after the opening of a new 504-bed hospital building, HUP Pavilion (PAV). We hypothesized that we would observe a reduction in HO-CDI after opening of PAV due to a reduced burden of C.difficile spores in the environment. Methods: We included NHSN reported HO-CDI rates for 28 months prior and 24 months after opening of PAV. Upon opening, patients were divided between the old building (HUP) and PAV. We included all patient units before and after opening. We created hierarchical models of HO-CDI rates using Stan Hamiltonian Monte Carlo (HMC) version 2.30.1, via the “cmdstanr” and “brms” packages with a GAM smooth function by month and intervention period with default, weakly-informative priors. Results: At baseline, there was an average of approximately 20,100 patient days per month, subsequently divided between HUP and PAV (mean 10,100 and 12,100 patient days per month). After opening of PAV, we observed a reduced HO-CDI rate (mean 0.21 vs 0.31 per 1000 patient days, P=0.01). When comparing the two specific buildings after opening of PAV, there was a greater reduction noticed in the old building (HUP) as compared to the new building (PAV) (0.12 vs 0.29 per 1000 patient days) (Figure 1). The predicted contrast in HO-CDI rate (Figure 2), shows no immediate change in HO-CDI after opening, however a sustained reduction estimated at 0.1 HO-CDI events per 1000 patient days for the duration of follow-up. Conclusions: We observed a reduction in HO-CDI rates after the opening of a new hospital building. The difference in HO-CDI rates between hospital buildings after the move is likely due to the concentration of high-risk patient cohorts within this building. Our findings suggests that there remains an opportunity to reduce HO-CDI through environmental hygiene. However, it is possible that other factors beyond surface environment contributed to an observed reduction in HO-CDI, including other concurrent infection control interventions that focused on smaller populations within the hospital. In future work we will investigate the durability of this observed effect with additional analyses including patient-level risk for HO-CDI.

Clostridioides difficile infection following COVID-19: A nationwide analysis using routine surveillance data in Wales

CDI incidence has increased in Wales from summer 2020 and has remained elevated. There is evidence of poorer outcomes from concurrent CDI and COVID-19 infections, but it is not clear if infection with COVID-19 directly impacts likelihood of CDI infection. We investigated the relationship between CDI and COVID-19 and the impact of secondary infections. We conducted two analytical studies using routine surveillance data: i) population level ecological case control study comparing CDI cases in the Welsh population by SARS-COV-2 exposure in the previous 90 days, ii) cohort study of COVID-19 cases by secondary infection presence, investigating CDI development within 90 days. Case control: 12% (196/1645) of CDI cases had prior COVID-19 and were twice as likely to have had COVID-19 compared to general population controls, when controlling for other infection history (OR 2.1, CI 1.8-2.5, p<0.0001). CDI cases were 8 times more likely to have had other infections, independent of COVID-19 history (OR 8.0, CI 7.0-9.0, p<0.001). 2% (2,255/137,620)) of the COVID-19 cohort developed >1 secondary infection, and <1% (185/137620) developed CDI within 90 days. CDI risk was four times higher in those with secondary infections, after age and sex adjustment (RR 4.6, CI 3.1 - 6.1, p<0.001). CDI risk increased with age and did not differ by sex. Findings suggest a relationship between COVID-19 and CDI. However, incidence of CDI following COVID-19 was a rare outcome generally, suggesting other factors are likely contributing to the increased rates of CDI observed since 2020.

Improving Data Quality from a Hematology Unit Hand Hygiene Observation Program

Background: For United States healthcare programs to be fully compliant with Joint Commission National Patient Safety Goal (NPSG) #7, organizations must implement and maintain a hand hygiene (HH) program that follows either the current Centers for Disease Control and Prevention (CDC) or the current World Health Organization (WHO) HH guidelines. Joint Commission standard IC.03.01.01 requires these organizations to provide metrics that evaluate the effectiveness of their program and program goals. Our center utilizes the direct observation method with the use of over 550 Hand Hygiene Observers (HHO) to collect our HH compliance. HHO are trained with a computer-based course that requires passing a post-education test. During fiscal year 2023 (FY23), Infection Control surveillance noted an increase in hospital-acquired infections (HAI) Clostridioides difficile infections (CDI), catheter-associated urinary tract infections (CAUTI), and multidrug-resistant organisms (MDRO) on our hematologic malignancy units (HM), which initiated an Infection Control (IC) investigation into possible causes. Increased rounding by our Infection Preventionist (IP) observed that HH compliance was much lower than unit HHO reported rates. Inquiries into this data discrepancy revealed barriers to accurate reporting, including HHO having low confidence in identifying and reporting non-compliant behavior. To that end, we conducted mandatory re-training of all HM HHO with the primary goal of improving the quality of our HH compliance data and addressing barriers with non-compliance reporting. Our secondary goal was to identify areas of improvement in institutional HH rates. Methods: In August 2023, 252 HM staff and HHO received detailed, in-person retraining by the HM IP. Training included reviewing the discrepancy in HHO and IP observations, potential causes of discrepancy, most commonly missed HH opportunities, examples of correct and incorrect HH practices, and addressing staff questions. Results: Following mandatory re-training of HM HHO, HH compliance for our HM units from September 2023 – December 2023 ranged from 89% to 98%, with increased reporting of non-compliance (Figure 1). A detailed dashboard was created that focused on HM HH compliance, containing the HHO observations and non-compliant reports. Conclusion: A one-time in-person retraining of HM HHO by our IP has led to an improvement in data quality, which is imperative for future quality improvement initiatives. Improving our HH data quality allowed IC to identify and provide actionable feedback to HM leaders, create targeted interventions to improve HAI rates, and improve patient safety. Future goals include retaining of all HHO and a HH campaign to ensure patient safety across our institution.

Reducing Clostridioides difficile Infections in a Medical Intensive Care Unit: A Multimodal Quality Improvement Initiative.

Clostridioides difficile (C. diff) infection causes significant morbidity for hospitalized patients. A large medical intensive care unit had an increase in C. diff infection rates. The aim of this project was to reduce the C. diff polymerase chain reaction (PCR) test positivity rate and the rate of C. diff PCR tests ordered. Rates were compared between preintervention (July 2017 to December 2019) and postintervention (January 2021 to December 2022) timeframes. Unit leadership led a robust quality improvement project, including use of quality improvement tools such as A3, Gemba walks, and plan-do-study-act cycles. Interventions were tailored to the barriers identified, including standardization of in-room supply carts; use of single-packaged oral care kits; new enteric precautions signage; education to staff, providers, and visitors; scripting for patients and visitors; and use of a C. diff testing algorithm. Statistical process control charts were used to assess for improvements. The average rate of C. diff PCR test positivity decreased from 34.9 PCR positive tests per 10 000 patient days to 12.3 in the postintervention period, a 66% reduction. The average rate of PCR tests ordered was 28 per 1000 patient days in the preintervention period; this decreased 44% to 15.7 in the postintervention period. We found clinically significant improvements in the rate of C. diff infection and PCR tests ordered as a result of implementing tailored interventions in a large medical intensive care unit. Other units should consider using robust quality improvement methods and tools to conduct similar initiatives to reduce patient harm and improve care and outcomes.

Understanding the Impact of Narrow Spectrum Beta-Lactam Use on Overall and Broad-Spectrum Antimicrobial Utilization in South Carolina

Background: The standardized antimicrobial administration ratio (SAAR) is a metric utilized to measure antimicrobial use within and between hospitals by comparing observed to predicted antimicrobial days of therapy. However, it remains unknown whether narrow-spectrum beta-lactam (NSBL) use adds to overall antimicrobial utilization or substitutes broad-spectrum agents. This muti-hospital cohort study examined the impact of NSBL use on overall antimicrobial utilization and the correlation between the use of NSBL and various broad-spectrum antimicrobial categories in South Carolina (SC) hospitals. Methods: SAARs were collected from all hospitals in SC that reported antimicrobial use (AU) data to the National Healthcare Safety Network (NHSN) between 2017 and 2021. SAARs collected included: overall SAAR, broad-spectrum agents predominantly used for hospital-onset infections (BSHO), broad-spectrum agents predominantly used for community-acquired infections (BSCA), NSBL, and antibacterial agents posing the highest risk for Clostridioides difficile infection (CDI). Category SAARs were combined to include data in both the adult intensive care unit (ICU) and adult wards using the formula: [(total observed antimicrobial days ICU + total observed antimicrobial days ward) / (total predicted antimicrobial days ICU + total predicted antimicrobial days wards)]. Pearson correlation coefficient (r) was used to examine the correlation between various SAARs categories. Results: A total of 38 hospitals in South Carolina reported AU to NHSN at least during one calendar year during the study period. The use of NSBL agents was negatively correlated with the use of BSHO (r = -0.596, p &lt; 0.001), BSCA (r = -0.543, p &lt; 0.001), and high-risk CDI antibiotics (r = -0.601, p &lt; 0.001). Moreover, the use of NSBL agents did not correlate with the overall SAAR (r = 0.008, p = 0.93), whereas the use of BSHO (r = 0.587, p &lt; 0.001), BSCA (r = 0.494, p &lt; 0.001), and high-risk CDI agents (r = 0.464; p &lt; 0.001) positively correlated with the overall SAAR. Conclusion: In South Carolina hospitals, the use of NSBLs does not contribute to additional antibiotic use overall as it seems to replace broad-spectrum antimicrobials in various categories. By de-escalating from broad-spectrum agents to NSBL agents, one can improve antimicrobial use without negatively impacting the overall SAAR. This observation encourages implementation of antimicrobial stewardship interventions that increase utilization of NSBLs, when appropriate, such as de-escalation of antimicrobial therapy among others without concerns for increasing the SAAR for overall antibiotic use.

Hospital-Onset Clostridioides difficile infection in chronic kidney disease patients

Introduction: Hospital-onset Clostridioides difficile infection (HO-CDI), reported as laboratory-identified (LabID) event, is common in patients with chronic kidney disease (CKD), especially those with end-stage renal disease (ESRD), and is associated with prolonged length of hospitalization and more severe disease. CKD patients are at increased of developing CDI due to frequent antimicrobial and healthcare exposures. The objective of this study was to assess recent trends of HO-CDI in patients on a nephrology unit at our academic, tertiary care institution. Methods: Retrospective cross-sectional study of patients with HO-CDI who were hospitalized on a nephrology unit between January 2021 to December 2023. Collected variables included: demographic data, characterization of HO-CDI risk factors, infection and diagnosis (including prior history of CDI, toxin versus nucleic acid amplification test [NAAT] positivity, number of loose stools), CDI rate (defined as CDI count/patient days x1000), standardized antimicrobial administration ratio (SAAR) for high-risk for CDI antimicrobials (defined by the National Healthcare Safety Network), and infection prevention and control (IPC) practices, including hand hygiene audit rates. Results: A total of 30 HO-CDI infections were reported on the nephrology unit [Table], with 8 occurring in 2021, 5 in 2022, and 17 in 2023. The median age of patients was 70.8 (range: 37-96) years, and most patients (57%) were female. The majority of patients were admitted from home (73%), and two patients (7%) had a history of CDI in the last 6 months. Among the CDI cases, 60% were NAAT positive and toxin negative, and only 50% had &gt;3 bowel movements (BM) within 24 hours prior to the positive test. Ten percent received promotility agents prior to testing. Most cases (77%) occurred when other CDI patients were on the unit. Hand hygiene compliance rates averaged 81% over the three-year period [Figure 1A]. Eight-four per cent of patients received antibiotics within 30 days of CDI diagnosis; SAAR was &gt;1 for quarters 2 and 4 in 2022, and quarter 1 in 2023 [Figure 1B]. Conclusion: On our nephrology unit, patients often had &lt; 3 BM within 24 hours of CDI diagnosis, and 60% of cases were toxin-negative, NAAT-positive, suggesting possible C. difficile colonization, rather than true infection. In addition, an elevated SAAR correlated with high CDI rates. Multicomponent interventions may be required to reduce the rates of HO-CDI in CKD patients. Opportunities include emphasis on diagnostic and antimicrobial stewardship, environmental cleaning and adherence to IPC practices, including hand hygiene.