bluuebunny/crossref_metadata_2025_split huggingface dataset:
782. Clostridioides difficile environmental contamination in hospitalized patients with diarrhea: a pilot study
Authors: Warren Bobby G , Turner Nicholas A , Addison Rachel , Nelson Alicia , Marden Samantha , Gamez Isabella , Smith Becky A , Polage Christopher R , Weber David J , Weber David J , Rutala William , Sickbert-Bennett Emily , Anderson Deverick J 
Published: January 2021

Abstract

Background
The relative contribution of Clostridioides difficile colonization or infection in contamination of the hospital environment is poorly understood.

Methods
We performed a prospective cohort study of patients with diarrhea who were tested for C. difficile infection via PCR and enzyme immunoassay (EIA) to compare C. difficile environmental contamination by test result. Patients were stratified into one of three cohorts: PCR-, PCR+/EIA+ or PCR+/EIA-. Environmental microbiological samples were taken within 24 hours of C. difficile cultures and again for two successive days for a total of three days. Patients were excluded if they had C. difficile infection in the past 6-weeks. Microbiological samples of surfaces were obtained with pre-moistened cellulose sponges from three locations (bathroom, adjacent to bed, and care areas) and processed using the stomacher technique. Ribotyping was completed on a subset of stool and environmental samples to measure concordance of isolates. CFU and recovery rates between arms were compared with a global ANOVA followed by pairwise comparisons using a Bonferroni adjustment.

Results
We enrolled 41 patients between November 2019 and March 2020. 7 patients were PCR+/EIA+, 8 were PCR+/EIA- and 26 were PCR- (Table 1). A total of 347 individual and 116 room samples were obtained. PCR+/EIA+ patient rooms had a higher average room burden (435.6 CFU (95%CI: 178.0-694.0)) compared to PCR+/EIA- (83.5 (-9.1-175.0), p&lt; 0.01) and PCR- rooms (17.1 (1.2-33.0), p&lt; 0.01); PCR+/EIA- and PCR- rooms were similar (p=0.83). PCR+/EIA+ patient rooms had a higher recovery rate (61%) compared to PCR+/EIA- (36%, p=0.64), although not statistically significant, and PCR- rooms (16%, p&lt; 0.01); PCR+/EIA- had a similar recovery rate to PCR- rooms (p=0.14) (Table 2). Of the rooms with both patient and environmental isolates, 79% of patient isolates had a concordant isolate recovered in the environment.
Table 1

Table 2

Conclusion
The amount of environmental contamination of PCR+/EIA+ patients was higher than both PCR+/EIA- and PCR- patients, however, the recovery rate of PCR+/EIA+ patients was similar to PCR+/EIA- patients. Subsequent larger trials are needed to expand on this pilot data to determine the difference, if any, between environmental contamination levels of these patient populations.

Disclosures
David J. Weber, MD, MPH, PDI (Consultant)
784. A Novel Method to Assess Virulence of Clostridioides difficile: Focus on C. difficile Ribotype 106
Authors: Almutairi Masaad , Garey Kevin W , Alnezary Faris S , Fallatah Saad , Gonzales-Luna Anne J , Alam M Jahangir , Begum Khurshida 
Published: January 2021

Abstract

Background
Clostridioides difficile ribotype (RT) 106 has emerged as one of the most commonly isolated strains in the USA and worldwide. However, studies investigating clinical outcomes associated with this strain are lacking. The purpose of this study was to compare disease severity, clinical cure, and recurrence rates associated with CDI caused by RT106 vs two other comparator strains.

Methods
This multicenter study (20 hospitals) assessed hospitalized patients infected with C. difficile RT106 compared to patients infected with a known hypervirulent strain (RT027) and a strain associated with less virulence (RT014-020). Electronic medical records were reviewed by investigators blinded to RT. Disease severity was calculated using the 2017 IDSA/SHEA guidelines, initial clinical cure was defined as resolution of symptoms by day 6 of treatment, and recurrence assessed 90-days after the initial positive toxin test. All isolates were ribotyped using PCR fluorescent ribotyping.

Results
A total of 380 patients with CDI aged 66 ± 17 years (Female: 59.5%; White: 70.5%) infected with RT 106 (115/380; 30.3%), RT027 (116/380; 30.5%), and RT014-020 (149/380; 39.2%) were included. Approximately half of the patients had severe CDI (47.6%). Disease severity was highest for RT027 (59.3%) followed by RT014-020 (45%), and RT106 (41.2%). Clinical cure rates were lowest for RT027 (74.8%) followed by RT106 (77.8%), and RT014-020 (85.5%). 90-day recurrence rates were highest for RT027 (20.7%) followed by RT106 (13.3%), and RT014-020 (8.7%). Compared to RT014-020, virulence increased with RT106 (OR:1.10; 95% CI: 0.67-1.8) and RT027 (OR: 2.0: 95% CI: 1.2-3.5) was noted.

Conclusion
Our novel analysis method established RT106 as a moderately virulent C. difficile strain vs. comparator ribotypes. This study presents a novel method for comparing clinical outcomes for emerging ribotypes.

Disclosures
Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)
786. Diagnostic stewardship of C difficile PCR testing with two step algorithm- A rural community hospital experience
Authors: Tirupathi Raghavendra , Freshman Ruth , Montoy Norma , Gross Melissa 
Published: January 2021

Abstract

Background
An estimated 15% of hospitalized patients are asymptomatic carriers of C. diff. Inappropriate testing can lead to over diagnosis, treatment, isolation & substantial financial penalties. Ours is a rural 310 bed hospital with nurse driven C. diff test ordering protocol. Due to inadvertent test ordering, we had an uptick in the HO-CDI incidence with rates as high as 0.94 per 1000 patient days in 2017. In order to streamline testing, we initiated an infection preventionist(IP) led diagnostic stewardship program which was implemented in two phases in 2017-2019

Methods
The phase 1 involved daily review by IPs regarding the legitimacy of PCR order for minimum 3 loose stools in 24 hours, use of laxatives, presence of symptoms.There were concerns nationally that then CDI risk adjustment model from NHSN in 2017 does not optimally account for the impact of specific CDI testing methods used by individual hospitals on CDI SIRs. Hence, in Jan 2018 NHSN’s MDRO/CDI Protocol stated “Results of the final test that are placed in the patient’s medical record should be used to determine whether event meets the CDI LabID defn”.This led to phase 2 in mar 2019 which involved two step testing which started with C diff PCR assay with positive test reflexed to the toxin A/B assay.

Results
During the first phase, and a full year of the protocol in 2018, the number of completed PCR tests decreased to 626 (compared to 940 PCR tests in 2016) with an 34% decrease. In the year following implementation of the Diagnostic Stewardship, HO CDI decreased from 60 in 2017 to 43 events in 2018 with a reduction of 28%. Subsequently, HO CDI further decreased in 2019 to 28 with a reduction of 35%. Since the start of the project in 2017, HO CDI have decreased 54% in total. The reduction in 314 C diff PCR tests in the first year[2017-2018] led to a savings of $8300 in lab supplies. No readmissions with C difficile infection documented within 30 days on patients who did not meet the criterion for testing. Significant decrease in the usage of C difficile antibiotics. After the start of the two step test, we have seen a precipitous drop in our HO-CDI rates to less than 0.3 per 1000 pt days by the end of 2019.
Quarterly comparison of HO CDI incidence for 2017-2020

HO CDI incidence before and following phase 1 and phase 2 interventions

C. difficile antibiotic use trends during intervention period

Conclusion
IP run diagnostic stewardship programs with two step tests are highly successful in streamlining testing and in discriminating infection from colonization

Disclosures
All Authors: No reported disclosures
789. Evaluation of Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence
Authors: Johnson Tanner M , Howard Amanda , Schwarz Kerry , Allen Lorna , Huang Misha , Bajrovic Valida , miller matthew 
Published: January 2021

Abstract

Background
Recurrent Clostridioides difficile infection (rCDI) within 180 days of the index episode is associated with a 33% increase in mortality and, to-date, few treatment options exist to prevent recurrent infection. Bezlotoxumab (BEZ) is a novel therapeutic option for the prevention of rCDI, yet limited data exist regarding its effectiveness in patients at high-risk for recurrence outside of controlled trials. This study aimed to compare BEZ to a historical standard of care (SoC) cohort for the prevention of rCDI in patients at high risk for recurrence.

Methods
A multi-center retrospective cohort study of patients within an academic health-system with one or more risk factors for rCDI. Patients received SoC with oral vancomycin (VAN) or fidaxomicin (FDX) from January 2015 to December 2017 or BEZ, in addition to oral SoC, from September 2017 to September 2019. The primary outcome was rCDI within 90 days of completion of oral VAN or FDX. Secondary outcomes included all-cause readmission, all-cause mortality, and safety events at 90 days.

Results
One-hundred twenty patients received BEZ in addition to SoC (n=47) or SoC alone (n=73). Mean (SD) age was 55 (16) years, mean (SD) number of lifetime CDI was 3 (2) episodes, and 30.8% of patients had severe CDI. Six (12.8%) patients in the BEZ cohort and thirty-one (42.5%) in the SoC cohort experienced rCDI at 90 days [OR (95% CI) = 0.20 (0.07-0.53), p=&lt; 0.01]. Incidence of all-cause mortality (2.1% vs 5.5%, p=0.67) and all-cause readmission (42.6% vs 56.2%, p=0.20) within 90 days were not statistically different between groups. Patient body weight, timing of BEZ administration, CDI severity, nor prior receipt of fecal microbiota transplantation significantly affected BEZ effectiveness. BEZ was well tolerated with one infusion-related reaction. There were no heart failure exacerbations among BEZ recipients and two exacerbations identified from control group.

Conclusion
In patients with at least one risk factor for rCDI, BEZ in addition to SoC was associated with lower rates of recurrent infection than SoC alone and may be a reasonable adjunct therapy in high risk patient populations.

Disclosures
matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)
790. Evaluation of Connecticut Medical Providers Concordance with 2017 IDSA/SHEA Clostridioides difficile Treatment Guidelines in New Haven County, 2017-2019
Authors: Luc Casey M , Olson Danyel M , Banach David , Hadler James , Clogher Paula 
Published: January 2021

Abstract

Background
Treatment guidelines for Clostridioides difficile infection (CDI) were updated by the Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) in 2017, notably for disease severity and antibiotic recommendations. Our objectives were to assess Connecticut medical providers’ concordance (2017-2019) with the 2017 update. The effect of guideline concordance on the risk of CDI recurrence was also assessed.

Methods
Using data from the Connecticut Emerging Infections Program’s CDI surveillance in New Haven County, severity and concordance were defined. For severity, white blood cell count and presence of megacolon and/or ileus were used. Concordant treatment was defined as receiving the recommended first-line antibiotic (vancomycin for adult patients, vancomycin or metronidazole for pediatric patients) for exactly 10 days. In univariate & multivariate analyses, significance was determined by a p-value of &lt; 0.05.

Results
Of 1,216 cases, concordance increased from 10.0% in 2017 to 36.9% in 2019. Concordance with first-line antibiotic increased from 40.2% in 2017 to 80.8% in 2019. Concordance was highest for fulminant cases (62.2%). The recurrence rate was 11.2% and highest for non-severe cases and older cases but was not significantly associated with concordance.
Concordance with selected treatment criteria by year, 2017-2019

Conclusion
From 2017 through 2019, CDI treatment in New Haven County increasingly was concordant with the updated 2017 IDSA/SHEA guidelines, but still low overall in 2019. Although concordance with treatment did not affect recurrence risk, close attention should be paid by medical providers to non-severe cases and older cases as they are at an increased risk for recurrence.

Disclosures
All Authors: No reported disclosures
791. Evaluation of NSAID Exposure as a Risk Factor for Clostridium difficile infection: A Propensity-Score-Matched Case-Control Study
Authors: Ressler Adam M , Patel Alieysa , Rao Krishna 
Published: January 2021

Abstract

Background
Exposure to certain medications, particularly antibiotics and proton pump inhibitors, has been associated with increased risk for Clostridium difficile infection (CDI). Studies have suggested an increased risk for CDI associated with exposure to certain non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a retrospective case-control study to evaluate the risk for CDI associated with NSAID use.

Methods
The population included 1338 patients tested for CDI from February–December 2016 at the University of Michigan. NSAID use within 30 days of CDI testing was determined by chart review. Both scheduled and as-needed NSAID use met the definition for exposure, but aspirin use alone did not. Additional clinical data such as comorbid disease and baseline laboratory parameters were extracted through electronic query. A random forest model imputed missing data. A propensity score for NSAID use was developed via logistic regression and included gender, back pain, baseline serum creatinine, osteoarthritis, rheumatoid arthritis, serum albumin, and use of anticoagulant or antiplatelet medications. Cases were matched 1:1 with C. difficile negative controls by propensity score, with a matching caliper of 0.2 x standard deviation of the logit of the score. The final study population consisted of 1256 cases and their matched controls, however 6 cases could not be matched to controls as none had scores within the matching caliper. Conditional logistic regression was used to compare cases to controls.

Results
NSAID use was similar between the two groups on unadjusted analyses. The adjusted, multivariable model demonstrates that non-aspirin NSAID use is not a significant risk factor for CDI (P =.816), after adjustment for comorbid disease burden, age, and history of prior CDI (Table). Older age and prior CDI were independent risk factors for CDI (Table).
Table Study population and modeling results

Conclusion
In this retrospective case-control study, non-aspirin NSAID use was not associated with an increased risk of CDI. To our knowledge, this is the first study of NSAID use as a risk factor for CDI that accounted for bias due to treatment assignment using a propensity score. Future studies should account for frequency or chronicity of NSAID use, which may affect the results.

Disclosures
Krishna Rao, MD, MS, Bio-K+ International, Inc. (Consultant)Merck and Co., Inc. (Research Grant or Support)Roche Molecular Systems, Inc. (Consultant)
792. Evaluation of Persistent Diarrhea and Recurrence Following Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection
Authors: Boton Noah , Ni Jiaqi , Mack Anthony , Eschenauer Gregory , Patel Twisha S , Kao John , Rao Krishna 
Published: January 2021

Abstract

Background
Patients treated for C. difficile infection (CDI) have high rates of recurrence. Fecal microbiota transplantation (FMT) is an effective therapy for patients with recurrent CDI. While highly successful, there are limited data to help clinicians predict which patients are more likely to have adverse outcomes following FMT. Here we aim to identify factors that are associated with recurrent CDI or persistent diarrhea following FMT for treatment of recurrent CDI.

Methods
At a large academic medical center, we conducted a retrospective cohort study of patients receiving their first FMT for recurrent CDI using product from a commercial stool bank. Patients were included if follow-up data on post-FMT outcomes were available. Through manual chart review, we collected information on patient demographics, comorbid disease burden, prior CDI, and antibiotic use prior to FMT. Outcomes included recurrent CDI and persistent diarrhea not from CDI, both within 90 days of FMT. Unadjusted and adjusted analyses via logistic regression were used to model the outcomes.

Results
This study included 81 subjects, of which 72 (89%) experienced no recurrence following FMT. In the multivariable model, the odds of recurrence decreased as BMI rose and with each 1-log increase in the duration of antibiotic therapy for CDI prior to FMT (Table). Among the 72 subjects not diagnosed with recurrent CDI following FMT, 26 (36%) experienced persistent diarrhea for which further work-up or therapy was recommended. History of irritable bowel syndrome (IBS) was the only predictor independently associated with persistent diarrhea while adjusting for age and number of prior CDI episodes (Table). IBS was also the most common etiology identified by the subjects’ clinical teams for persistent diarrhea following FMT.
Table. Multivariable models of adverse outcomes following FMT for CDI

Conclusion
We found FMT for CDI at our center to be effective in curing CDI without subsequent recurrence, at a level similar to what is seen from randomized controlled trials. Higher BMI and longer duration of antibiotic therapy for CDI prior to FMT may be protective against recurrence. Still, a significant proportion of patients experienced persistent non-C. difficile related diarrhea, and patients with a history of IBS were more likely to have persistent diarrhea after FMT.

Disclosures
Krishna Rao, MD, MS, Bio-K+ International, Inc. (Consultant)Merck and Co., Inc. (Research Grant or Support)Roche Molecular Systems, Inc. (Consultant)
796. Improving Clostridioides difficile Infection Treatment and Outcomes Using a Web-based Tool to Support a Care Coordination Intervention
Authors: McKoy J Nikki , Biondolillo Madeleine , House John A , Kunz Emily , Safo Stella 
Published: January 2021

Abstract

Background
Clostridioides difficile infection (CDI) is a highly burdensome disease, affecting 500,000 Americans each year. Despite extensive efforts to prevent and treat CDI, variability remains in the treatment guidelines, particularly as new medications are released. Treating CDI is particularly difficult, as approximately 25% of infected individuals experience recurrent CDI (rCDI).

Methods
We used a pre-post design to measure the impact of an intervention on rCDI, CDI readmission, and guideline-adherent treatment rates in adult patients who were admitted with or contracted CDI in the hospital. The intervention included the following:
• Web-based performance platform delivering education and care coordination support
• CDI care coordination for 8 weeks post-discharge (Figure 1)
• Education and tools for addressing CDI guidelines, workflow needs, and patient engagement
• Best practice sharing through peer-to-peer discussion calls
Patient Contacts

Results
Among the 77 patients consented in the Pre-Intervention period, 12 (15.6%) patients reported a recurrence of CDI, compared to 6 (15.4%) of the 39 Intervention patients who provided a response (P = 0.98). While a total of 55 patients were consented in the Intervention period, none reported a readmission for CDI, however 9 (11.7%) of Pre-Intervention patients reported a readmission for CDI (P = 0.03). There was a significant difference (P &lt; 0.001) between the use of appropriate treatment, as defined by the 2018 SHEA/IDSA guidelines, between the Pre-Intervention and Intervention groups (55.8% vs. 94.3%).

Conclusion
A comprehensive multi-disciplinary team approach to preventing rCDI, including post-discharge care coordination, provides support to patients and caregivers. Future research is needed to evaluate how web-based tools, like those used in this study, could engage patients in the management of CDI and rCDI. Interventions aimed at improving the care of these patients may reduce recurrences and rehospitalizations.

Disclosures
All Authors: No reported disclosures
798. Metronidazole Exposure Prior to Clostridiodes difficile Infection (CDI) is a Risk Factor for Severe C. difficile Disease in Cancer Patients
Authors: Francisco Denise Marie A , Zhang Liangliang , Jiang Ying , Olvera Adilene , Guevara Eduardo Yepez , Garey Kevin W , Peterson Christine , Dillon Ryan J , Obi Engels N , Okhuysen Pablo C 
Published: January 2021

Abstract

Background
Antibiotic use is a risk factor for CDI. Few studies have correlated use of prior antibiotics with CDI severity in cancer patients. This study identified clinical and microbiology risk factors associated with severe CDI in patients with cancer. We hypothesized that previous antibiotic exposure and microbiome composition at time of CDI presentation, are risk factors for severe disease in cancer patients.

Methods
This non-interventional, prospective, single-center cohort study examined patients with cancer who had their first episode or first recurrence of CDI between Oct 27, 2016 and Jul 1, 2019. C. difficile was identified using nucleic acid amplification testing. Multivariate analysis was used to determine significant clinical risk factors for severe CDI as defined in the 2018 IDSA/SHEA guidelines. Alpha, and beta diversities were calculated to measure the average species diversity and the overall microbial composition. Differential abundance analysis and progressive permutation analysis were used to single out the significant microbial features that differed across CDI severity levels.

Results
Patient (n=200) demographics show mean age of 60 yrs., 53% female, majority White (76%) and non-Hispanic (85%). Prior 90 day metronidazole use (Odds Ratio OR 4.68 [1.47-14.91] p0.009) was a significant risk factor for severe CDI. Other factors included Horn’s Index &gt; 2 (OR 7.75 [1.05-57.35] p0.045), Leukocytosis (OR 1.29 [1.16-1.43] p&lt; 0.001), Neutropenia (OR 6.01 [1.34-26.89] p0.019) and Serum Creatinine &gt;0.95 mg/dL (OR 25.30 [8.08-79.17] p&lt; 0.001). Overall, there were no significant differences in alpha and beta diversity between severity levels. However, when identifying individual microbial features, the high presence of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were associated with protection from severe CDI (p&lt; 0.05).
Table 1 - Results of multivariate logistic regression analysis of factors associated with severe CDI

Figure 1. Microbiome features identified by progressive permutation analysis as seen in a volcano plot.

Conclusion
A number of risk factors for severe CDI were identified among this population, including prior 90 day metronidazole use. Also, increased relative abundance of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were linked to protection from severe CDI. Reducing metronidazole use in patients with cancer may help prevent subsequent severe CDI.

Disclosures
Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee) Engels N. Obi, PhD, Merck & Co. (Employee)