762. Real-World Utilization of C. difficile Drug Treatments and Associated Clinical Outcomes in a US Hospital System

Abstract Background IDSA recommends use of fidaxomicin or oral vancomycin for treatment of initial episode or first recurrence of Clostridioides difficile infection (CDI). This study aimed to evaluate impact of a clinical decision support order set driving appropriate use of fidaxomicin on utilization of CDI drug treatments and associated clinical outcomes. Methods This was a retrospective, quasi-experimental study evaluating CDI therapies pre- (8/2016-11/2017) and post- (5/2018-1/2020) CDI order set implementation at a level-one trauma center located in Virginia. Admitted adult patients were included if CDI testing was positive for a 1st or 2nd episode and received active CDI treatment. Exclusions included fulminant CDI and CDI diagnosis by PCR with < 3 bowel movements or laxative use within 24 hours. The primary outcome was CDI recurrence within 30 days of completing therapy in patients who achieved clinical cure. Secondary outcomes were evaluated at 30 and 90 days and included sustained response and CDI-related readmissions. Results After screening, 186 patients in the pre-group and 187 in the post-group were included. Median age was 68 [59-77], most patients had an initial CDI episode (88.2%) and were diagnosed with severe CDI (50.7%). Baseline characteristics were similar between each group on Charlson comorbidity index, ICU admission, CDI risk factors, and concomitant antibiotic use. Primary treatment options in the pre-group were most commonly metronidazole 47.9% and oral vancomycin 50.5%, and in the post-group were fidaxomicin 56.7% and oral vancomycin 41.7% (Figure 1). CDI recurrence rates at 30 days post-index medication (17.2% vs. 6.3%, p=0.004) were lower in the post-group (Table 1). Clinical cure (84.4% vs. 94.1%, p=0.002) and sustained response at 90 days (55.9% vs. 73.3%, p< 0.001) were higher in the post-group. CDI recurrence rates at 90 days and CDI-related readmissions at 30 and 90 days were also lower in the post group. Figure 1. CDI Treatment Utilization Table 1. Clinical Outcomes Conclusion Implementation of the CDI order set increased fidaxomicin use and was associated with a decrease in CDI recurrences and CDI-related readmissions and increase in clinical cure and sustained response. Findings suggest increased first-line use of fidaxomicin results in better clinical outcomes. Disclosures Lauren McDaniel, Pharm.D., BCIDP, Merck Sharp & Dohme Corp (Grant/Research Support) Nathan Everson, Pharm.D., BCIDP, AAHIVE, Merck & Co. (Grant/Research Support) Melissa White, PharmD, Merck Sharpe & Co (Grant/Research Support) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder) Yiyun Chen, PhD, Merck & Co., Inc (Employee) Rose Kohinke, PharmD, Merck Sharpe & Co (Research Grant or Support)


Host Intestinal Defenses Against Clostridioides difficile Infection in Chemotherapy Patients
Claire Weinstein, BA 1 ; Racheal Wilkinson, BS, MLS 1 ; Senu Apewokin, MD 1 ; 1 University of Cincinnati, Cincinnati, Ohio Session: P-36. HAI: C. difficile Background. Clostridioides difficile infection (CDI) is a common complication in patients undergoing cancer treatment with cytotoxic chemotherapy. Exposure to antibiotics or chemotherapy disrupts the microbiome by killing protective intestinal flora which consequently promotes C. difficile spore germination and disease. The host defense against CDI includes colonization resistance conferred by the healthy microbiome and innate defenses provided by intestinal epithelial cells. One protective factor secreted by Paneth cells of the intestinal epithelium is lysozyme, an enzyme that degrades the cell walls of Gram-positive bacteria such as C. difficile. We hypothesized that chemotherapy-induced mucosal barrier injury and the resultant death of Paneth cells leads to decreased production of lysozyme. We thus sought to examine changes in lysozyme concentration in stools of chemotherapy patients.
Methods. We collected stool samples from six patients undergoing cancer treatment at four different time points. The first stool sample corresponded to the day prior to the start of chemotherapy (day zero). We then performed ELISA assays to determine the lysozyme concentration for each stool sample.
Results. On day zero, the lysozyme levels (n=6) averaged 268.1 ± 131.7 ng/mL. Over the course of chemotherapy, the lysozyme levels decreased 78.70 ± 24.19% from the starting value. The lowest values were observed around days 5 through 11 for most patients, coinciding with when they were most neutropenic around day 11. One of the patients developed CDI on day 5 and experienced more fluctuating lysozyme levels thereafter. On the day that the patient developed CDI, lysozyme was measured as 6.63 ng/mL. Throughout treatment, 3/6 patients showed recovery of lysozyme production with white blood cell recovery.
Conclusion. Our data indicate that chemotherapy causes decreased concentrations of lysozyme in stool. Low lysozyme levels could in part account for the increased susceptibility to CDI during chemotherapy. Future experiments will include bioinformatics analyses to determine how the microbiome changes in response to chemotherapy. Together, these experiments will inform our approach to determining patient susceptibility to chemotherapy-associated CDI.
Disclosures. Background. IDSA recommends use of fidaxomicin or oral vancomycin for treatment of initial episode or first recurrence of Clostridioides difficile infection (CDI). This study aimed to evaluate impact of a clinical decision support order set driving appropriate use of fidaxomicin on utilization of CDI drug treatments and associated clinical outcomes.
Methods. This was a retrospective, quasi-experimental study evaluating CDI therapies pre-(8/2016-11/2017) and post-(5/2018-1/2020) CDI order set implementation at a level-one trauma center located in Virginia. Admitted adult patients were included if CDI testing was positive for a 1 st or 2 nd episode and received active CDI treatment. Exclusions included fulminant CDI and CDI diagnosis by PCR with < 3 bowel movements or laxative use within 24 hours. The primary outcome was CDI recurrence within 30 days of completing therapy in patients who achieved clinical cure. Secondary outcomes were evaluated at 30 and 90 days and included sustained response and CDI-related readmissions.
Results. After screening, 186 patients in the pre-group and 187 in the post-group were included. Median age was 68 [59-77], most patients had an initial CDI episode (88.2%) and were diagnosed with severe CDI (50.7%). Baseline characteristics were similar between each group on Charlson comorbidity index, ICU admission, CDI risk factors, and concomitant antibiotic use. Primary treatment options in the pre-group were most commonly metronidazole 47.9% and oral vancomycin 50.5%, and in the post-group were fidaxomicin 56.7% and oral vancomycin 41.7% (Figure 1). CDI recurrence rates at 30 days post-index medication (17.2% vs. 6.3%, p=0.004) were lower in the post-group (Table 1). Clinical cure (84.4% vs. 94.1%, p=0.002) and sustained response at 90 days (55.9% vs. 73.3%, p< 0.001) were higher in the post-group. CDI recurrence rates at 90 days and CDI-related readmissions at 30 and 90 days were also lower in the post group.

Impact of Two-Step Testing Algorithm on Hospital-onset Clostridioides difficile Infections and Oral Vancomycin Prescription Practices at an Academic Medical Center
Mary Joyce Wingler, PharmD 1 ; David A. Cretella, PharmD 1 ; Jason Parham, MD, MPH, FACP, FIDSA 1 ; Bhagyashri Navalkele, MD 1 ; 1 University of Mississippi Medical Center, Jackson, MS Session: P-36. HAI: C. difficile Background. Clostridioides difficile infection (CDI) is one of the leading causes of hospital -onset (HO) infections. Clinically distinguishing true CDI versus colonization with C.difficile is challenging. We implemented a two-step testing algorithm to discriminate true CDI from colonization then evaluated the effect on rate of HO CDI and oral vancomycin.
Methods. In May 2020, a two-step testing algorithm was implemented utilizing C. difficile PCR and enzyme immunoassay (EIA) glutamate dehydrogenase ( Figure  1). Rates of HO CDI and use of oral vancomycin was compared in the three quarters preceding and after this intervention (July 2019-March 2020 and July 2020-March 2021, respectively). HO CDI was defined based on National Healthcare Safety Network (NHSN) Laboratory Identified (LabID) event as last positive C.difficile test result performed on a specimen collected >3 calendar days after admission to the facility. HO CDI rates were assessed based on Standardized Infection Ratio (SIR) data and antimicrobial use was reported in days of therapy (DoT) per 1000 patient days.

Figure 1. Two-Step Testing Algorithm for Diagnosing Clostridioides difficile infection
Results. During the pre-intervention period 30 HO CDI cases were reported compared to 9 cases in the post-intervention period (p=0.02) (Figure 2). There was a non-statistically significant reduction in CDI SIR in post-intervention period (0.133 vs. 0.305, p=0.11). Oral vancomycin use was similar in the pre-and post-intervention periods (3.89 vs. 3.84, p=0.96). Fidaxomicin use was rare (< 0.2 DoT/1000 pt days).
Of 26 HO C.difficile colonized patients in post-intervention period, 14 (54%) patients received oral vancomycin treatment. Infectious diseases was consulted on 7/14 and recommended discontinuation of treatment in 3 while treatment was continued for other patients based on clinical status and immunocompromising conditions. Conclusion. We successfully reduced our HO CDI infections and SIR below national average after implementation of two-step testing algorithm for CDI. There was no impact on the rate of oral vancomycin use. We observed at 54% rate of treatment for patients categorized as likely colonization. Provider education and stewardship interventions are necessary to reduce inappropriate use of oral vancomycin in colonized patients.
Disclosures. Background. Exposure to antimicrobials is a known risk factor for Clostridium difficile infection (CDI). Antimicrobials cause collateral damage by disrupting the natural intestinal microbiota allowing for C.difficile to thrive and production of C.difficile toxins. Probiotics could modulate the onset and course of CDI. However, the data on probiotics for the prevention of CDI is conflicting.
Methods. We conducted an IRB approved retrospective cohort study at a 340bed community hospital. All hospitalized patients from August 1, 2017 through July 31, 2020 were evaluated for enrollment. Patients were included if they received at least one dose of intravenous (IV) antibiotic and had a length of stay of at least 3 days. Patients were excluded if they were younger than 18 years, or if they had a positive C.difficile polymerase chain reaction test before antibiotics were started. The primary outcome was the incidence of healthcare facility-onset Clostridium difficile infection (HO-CDI). Descriptive statistics were used to analyze demographics data, and the primary outcome of HO-CDI was analyzed using Fisher's exact test and multiple logistic regression.
Results. A total of 20,257 patients received IV antibiotics during the study time frame. Of these, 2,659 patients received probiotics. Primary outcome of HO-CDI occurred in 46 patients in the IV antibiotics alone cohort (0.26%) and 5 patients in the probiotics plus IV antibiotics cohort (0.19%). The difference in HO-CDI between these two groups was not statistically significant, p=0.677. A multiple logistic regression was performed to see the impact of proton pump inhibitor use, age, ICU admission, Charlson Comorbidity Index, probiotic use and CDI in the past 12 months on the primary outcome. C.difficile infection in prior 12 months [OR 3.37, 95%CI 1.04-10.97] and ICU admission [OR 1.81, 95%CI 1.02-3.19] were associated with higher CDI. The addition of probiotics to patients on IV antibiotics did not exhibit a protective effect [OR 0.72, 95% CI 0.28-1.81].
Conclusion. The addition of probiotics to standard of care was not beneficial in the prevention of HO-CDI. We endorse robust antibiotic stewardship practices as part of the standard of care bundle that institutions should employ to decrease the incidence of HO-CDI. Disclosures.