CDI Risk Research Articles

Examining the impact of the COVID-19 pandemic on hospital-associated Clostridioides difficile infection.

To evaluate the impact of changes in the size and characteristics of the hospitalized patient population during the COVID-19 pandemic on the incidence of hospital-associated Clostridioides difficile infection (HA-CDI). Interrupted time-series analysis. A 576-bed academic medical center in Portland, Oregon. We established March 23, 2020 as our pandemic onset and included 24 pre-pandemic and 24 pandemic-era 30-day intervals. We built an autoregressive segmented regression model to evaluate immediate and gradual changes in HA-CDI rate during the pandemic while controlling for changes in known CDI risk factors. We observed 4.5 HA-CDI cases per 10,000 patient-days in the two years prior to the pandemic and 4.7 cases per 10,000 patient-days in the first two years of the pandemic. According to our adjusted segmented regression model, there were neither significant changes in HA-CDI rate at the onset of the pandemic (level-change coefficient = 0.70, P-value = 0.57) nor overtime during the pandemic (slope-change coefficient = 0.003, P-value = 0.97). We observed significant increases in frequency and intensity of antibiotic use, time at risk, comorbidities, and patient age before and after the pandemic onset. Frequency of C. difficile testing did not significantly change during the pandemic (P= 0.72). Despite large increases in several CDI risk factors, we did not observe the expected corresponding changes in HA-CDI rate during the first two years of the COVID-19 pandemic. We hypothesize that infection prevention measures responding to COVID-19 played a role in CDI prevention.

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.

658. Oral Vancomycin Taper for First Occurrence of Clostridioides difficile Compared to Standard of Care: An Observational Retrospective Matched Cohort Study

Abstract Background Clostridioides difficile infection (CDI) recurrence rates may be reduced with fidaxomicin, but financial barriers can limit access. Tapered and/or pulsed oral vancomycin is recommended in patients with recurrent CDI, however there is currently limited data for use in treating initial CDI. Methods Multicenter retrospective propensity-matched cohort study in patients ≥ 18 years old hospitalized with a first occurrence of CDI from 6/18/2018 – 12/21/2021 conducted at Norton Healthcare in Louisville, Kentucky. Standard of care (SOC) was receipt of oral vancomycin for 10-14 days compared to a standardized oral vancomycin taper (Figure 1). Subjects were matched based on age &amp;lt; or ≥ 65 and receipt of non-CDI antibiotics during index hospitalization or within 6 months post-discharge. Selected baseline characteristics and receipt of CDI and non-CDI antibiotics were collected. Non-CDI antibiotics were stratified by high, medium or low risk for CDI. The primary outcome was CDI recurrence within 6 months of hospital discharge. Secondary outcomes included time to recurrence, recurrence rates stratified by age group &amp;lt; or ≥ 65 years, CDI severity of illness per IDSA guidelines and all-cause mortality within 6 months of hospital discharge. Categorical variables were analyzed using Chi-squared and Fisher’s exact tests as appropriate. Standardized Oral Vancomycin Taper Results Recurrence rates at 6 months were 5.3% (4/75) in the taper arm and 28% (21/75) in the SOC arm (p=0.002). All-cause mortality was 20% (15/75) in the taper arm and 5.3% in the SOC arm (p=.026). Severe/fulminant CDI occurred in 49.3% of the taper arm and 58.7% of the SOC arm (p=0.53). Both groups received antibiotics at the same rate based on matching, and rates of antibiotics considered high risk for CDI were similar at 65% in the taper and SOC groups (65% vs. 61.3%, p=0.809). More patients in the taper arm were immunocompromised (25.3% vs 9.3%, p=0.029). Conclusion A significantly lower rate of CDI recurrence was observed at 6 months with tapered oral vancomycin coupled with higher all-cause mortality in patients being treated for first CDI. Additional information is needed to elucidate the clinical utility of this approach. Disclosures Ashley M. Wilde, PharmD, BCIDP, Pfizer: Grant/Research Support

691. Association between Clostridioides difficile Colonization, Rectal Swab NAAT Positivity, and Environmental Contamination

Abstract Background Clostridioides difficile (CD) colonization is common among hospitalized patients. Screening for toxigenic CD (TCD) colonization with rectal swab nucleic acid amplification tests (NAAT) may identify people at risk for CDI and help prevent onward TCD transmission, especially in immunocompromised patients with long hospitalizations. The study objective was to test whether rectal swab NAAT could detect TCD colonized patients and whether NAAT results identify patients that contribute to environmental contamination. Methods This was a prospective cohort study on two BMT/Leukemia units. Stool specimens, rectal swabs, and environmental swabs (bedrail, room sink, keyboard) were collected from patients at admission and weekly and cultured semi-quantitatively for TCD. NAAT (Cepheid) was performed on rectal swabs (eSwabs; Copan Diagnostics). The relationship between stool TCD concentration, NAAT Ct, and a positive environmental culture was evaluated using univariate logistic regression. Bleach was used for daily and terminal discharge cleaning of all rooms. Toxigenicity was determined by detection of tcdA or tcdB by whole genome sequencing (WGS). Results From January 2019 - July 2019, 659 stool specimens and 495 rectal swabs were collected from 384 patients. Specimens from 554 patient-days were cultured and 126 (23%) were positive. Of those, 88 (70%) were TCD. 21 of 987 (2%) environmental swabs were TCD positive; 18 (86%) were from bedrails. Among 61 unique patient calendar days with paired rectal swab NAAT and stool culture results (paired samples), overall sensitivity of rectal swab NAAT to detect toxigenic CD colonization compared to culture was 44%, with 4/16 (25%) of people colonized with &amp;gt; 0 - &amp;lt; 10,000 CFU/g of TCD and 7/9 (78%) with ≥ 10,000 CFU/g TCD (Figure 1). There was no relationship between stool culture or rectal swab NAAT result and risk of a positive environmental swab (Figure 2). Figure 1. Toxigenic C. difficile semi-quantitative culture and rectal swab NAAT on paired patient-day of specimen collection (N=61 patient-days) Figure 2. Toxigenic C. difficile semi-quantitative stool and rectal swab NAAT results and environmental contamination by paired patient-day of specimen collection Conclusion Rectal swab NAAT may not be sufficiently sensitive to screen for TCD colonization that contributes to environmental contamination. Disclosures Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support

686. Management and Outcomes of Patients Referred to a Specialty Clinic for C. difficile Infection

Abstract Background Clostridioides difficile infection (CDI) poses an urgent threat in the United States with an estimated 223,900 cases of hospitalization and 12,800 estimated deaths in 2017. CDI manifestations range from diarrhea, pseudomembranous colitis, to fulminant colitis. Due to spores that are unaffected by current antimicrobial therapies, recurrence remains a common challenge. Patients with 2 or more episodes have an estimated 40-65% rate of recurrence. We reviewed the management and outcomes of patients referred to our specialty CDI clinic. Methods A retrospective chart review was conducted on all new patients presenting to the Loyola University Medical Center CDI clinic between 01/01/2021 and 12/31/2021. Each chart was reviewed for demographic information, comorbidities that may confound diagnosis, and characteristics that place the patient at high risk of recurrent CDI. Visits were characterized by the number of prior CDI episodes, timeline of recurrences, and prior therapies used. 30- and 60-day symptom recurrence were assessed. Results A total of 48 new patients presented to the CDI clinic. The median age was 63 years, 64.5% were white, and 64.5% were female. Patients presenting with recurrent CDI accounted for 79% of cases (38/48), with 48% (13/48) of patients having two or more recurrences. The most common decision for initial management was to not give further antimicrobials and monitor for symptoms (35%). 12% of patients only required monitoring while 23% of patients had a questionable CDI diagnosis and were referred elsewhere for further evaluation. For the 30 patients who received treatment, vancomycin or fidaxomicin tapers were selected 73% (22/30) and bezlotoxumab 20% (6/30) of the time. 8.6% (2/23) of patients with a history of two or more CD episodes had recurrence. Overall, patients experienced a subsequent recurrence rate of 12.5% (6/48) and 15% (7/48) at 30 and 60 days, respectively. The number of times each management approach was selected for initial patient appointments. The number of times each treatment regimen was selected when a patient was deemed to need antibiotic therapy. The percentage of patients who had either recurrence or resolution at 60 days after the end of therapy. Conclusion CDI is a difficult-to-treat infection with many patients suffering from multiple recurrences. Dedicated outpatient follow-up is important for monitoring therapy and excluding alternate etiologies. Expert management of CDI through a dedicated clinic results in lower recurrence for high-risk patients and spared 35% of patients further antimicrobial exposure. Disclosures Larry H. Danziger, PharmD, Ferring Pharmacetuicals: Advisor/Consultant Andrew M. Skinner, MD, Academy for Continued Healthcare Learning: Honoraria|American Society of Healthcare Pharmacists: Honoraria|Ferring Pharmaceuticals: Honoraria|MJH Life Sciences: Honoraria

Impact of COVID-19 Pandemic on Healthcare-Associated Infections: A Systematic Review and Meta-Analysis.

This study investigated how the Coronavirus Disease 2019 (COVID-19) pandemic has affected the rate of healthcare-associated infections (HAIs). PubMed, Scopus and Google Scholar were searched to identify potentially eligible studies published from December 2019 to September 2022. A random effect model was used to determine the changes in the rate of HAIs during the pandemic. Thirty-seven studies, mostly from the United States (n = 13), were included. Fifteen studies described how the pandemic affected the rate of CLABSIs and CAUTIs, and eight of them showed a significant increase in CLABSIs. The risk of CLABSIs and CDIs was 27% (pooled odds ratio [OR]: 0.73; confidence interval [CI]: 0.61-0.89; p < 0.001) and 20% (pooled OR: 1.20; CI: 1.10-1.31; p < 0.001) higher during the pandemic compared to before the COVID-19 pandemic period, respectively. However, the overall risk of HAIs was unaffected by the pandemic (pooled OR: 1.00; 95 CI: 0.80-1.24; p = 0.990). Furthermore, there were no significant changes in the risk of CAUTIs (pooled OR: 1.01; 95 CI: 0.88-1.16; p = 0.890), and SSIs (pooled OR: 1.27; CI: 0.91-1.76; p = 0.16) between the two periods. The COVID-19 pandemic had no effect on the overall risk of HAIs among hospitalized patients, but an increased risk of CLABSIs and CDI were observed during the pandemic. Therefore, more stringent infection control and prevention measures and prudent interventions to promote the rational use of antibiotics are warranted across all healthcare facilities to reduce the burden of HAIs.

332 Gut reaction: Faecal Microbiota Transplantation in a multimorbid older patient with recurrent Clostridium Difficile Infections

Abstract Background Clostridium Difficile Infection (CDI) is a leading cause of hospital-acquired morbidity and mortality, especially among older adults. Advancing age and in particular those older adults with End-Stage Kidney Disease (ESKD) are at an increased risk for recurrent CDI due to frequent antibiotic exposure, extended hospitalisations, and compromised immunity. This report presents a unique case of an 85-year-old male with a complex medical history that also includes ESKD on haemodialysis, chronic myelomonocytic leukaemia, hypertension, Barrett’s oesophagus, and secondary hyperparathyroidism. He experienced 7 hospital admissions over a period of 12 months due to recurrent CDI, despite treatment with metronidazole, vancomycin and fidaxomicin, as well as prophylactic fidaxomicin. This amounted to a total hospital stay of 53 days. Interestingly his CDI was not associated with antibiotic use. Methods After consultations involving a multidisciplinary team of nephrology, infectious diseases, gastroenterology, geriatrics and haematology specialists, the decision was made to proceed with Faecal Microbiota Transplantation (FMT). Based on the patient’s preference the FMT was performed via a colonoscopy. Results The success of FMT in this case was notable. The patient has experienced no further CDI or immediate complications post-FMT, demonstrating the effectiveness and safety of this approach even in a complex clinical scenario. Conclusion In an era where recurrent CDI poses significant challenges to older patient health, especially in those with multi-morbidity like our patient, and where standard antibiotic treatments fail, this report underscores the importance of considering FMT as a potential treatment option as well as highlighting its safety in older adults. Hence, this case adds valuable insights to the growing literature advocating FMT use in managing recurrent CDI in complex older adults, potentially directing future clinical decisions and treatment guidelines.

Risk factors for recurrent healthcare-facility associated Clostridioides difficile infection in a Swedish setting

ObjectiveThe objectives were to determine the risk factors for recurrent healthcare facility-associated Clostridioides difficile infection (HCF-CDI) in a high CDI incidence, low antibiotic use setting and to determine if length of cefotaxime exposure is a risk factor for recurrent HCF-CDI. MethodsThe risk factors for recurrent HCF-CDI were evaluated with a retrospective nested case control study based on chart reading. The risk factors were evaluated univariately and multivariately. Length of risk antibiotic exposure was evaluated further in a subanalysis. ResultsRisk factors for recurrent HCF-CDI were renal insufficiency (25.4% of cases compared to 15.4% of controls p = 0.006) and metronidazole treatment of initial CDI episode (88.4% compared to 71.7% p = 0.01). Exposure to cefotaxime and risk for recurrent CDI showed a dose-dependent relationship (linear by linear p = 0.028). ConclusionsRenal insufficiency and metronidazole treatment were independent risk factors for recurrent HCF-CDI in our setting. The relationship between cefotaxime exposure and risk for recurrent HCF-CDI, dose-dependent, could be evaluated further in a setting with high cefotaxime use.

A233 OUTCOMES OF CLOSTRIDIOIDES DIFFICILE INFECTION IN SURGICAL PATIENTS: RESULTS FROM NATIONAL INPATIENT SAMPLE 2016-2019

Abstract Background Clostridioides difficile infection (CDI) is the most common nosocomial infection and is associated with significant morbidity and mortality. Purpose We aimed to identify the burden of CDI in patients undergoing common gastrointestinal (GI) surgical procedures in a national inpatient cohort, as GI surgeries have been thought to be a risk factor for CDI. Method We used the National Inpatient Sample (NIS) database from Unites States for the years 2016-2019 for this study. We included adult patients (age ≥ 18), who underwent common GI surgeries (identified using ICD-10 procedure codes), and among them identified patients with diagnosis of CDI. Outcomes assessed included risk of CDI among different surgeries, inpatient mortality, length of stay (LOS) and cost of hospitalization using regression analyses Result(s) From 2016 to 2019, an estimated total of 4,438,778 patients were hospitalized and underwent any of the studied GI surgeries. CDI was reported in 32,180 admissions (0.72%). Median age for CDI was higher than non-CDI patients (66 vs 56, p&amp;lt;0.001). Incidence of CDI was 2.5 times higher in patients admitted emergently compared to elective admissions (1.00% vs 0.40%, p&amp;lt;0.0001). Among all surgeries, the incidence of CDI was the highest for small bowel resection at 2.1% followed by partial esophagectomy at 1.6% and partial colectomy at 1.4%. Logistic regression analysis showed the patients undergoing esophagectomy had the highest risk with adjusted Odds Ratio (aOR) of 2.48, (95% CI 2.01 – 3.07, p&amp;lt;0.0001), followed by pancreatectomy with aOR 2.03 (95% CI 1.91 – 2.16, p&amp;lt;0.0001). Overall, surgical patients with CDI had a significantly higher in-patient mortality compared to non-CDI patients (8.2% vs 1.4%, p&amp;lt;0.0001). Logistic regression analysis showed an increased risk of inpatient mortality with CDI, with aOR 1.36, 95% CI 1.30 – 1.42, p&amp;lt;0.0001. Median LOS for surgical patients with CDI was higher than non-CDI patients (14 days vs 3 days, p&amp;lt;0.0001). The linear regression analysis for length of stay showed that among patients undergoing surgical procedures, CDI was associated with an increased LOS with beta of 8.39 days ± SE 0.04 (95% CI 8.31 – 8.46, p&amp;lt;0.0001). The mean cost of hospitalization for surgical patients with CDI was higher than non-CDI patients ($90,590 vs $31,702, p&amp;lt;0.0001) after adjusting for inflation over the four-year period. The linear regression analysis showed that CDI was associated with an increased cost of hospitalization with a beta of $25,343 ± SE 166 (95% CI 25,017 – 25,670, p&amp;lt;0.0001). Conclusion(s) CDI among GI surgeries leads to increase in inpatient mortality, length of stay and cost of hospitalization. Although the rate of CDI is showing a downwards trend, its impact on these outcome measures makes it an important complication to prevent and promptly treat in these surgical patients. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Fidaxomicin for the Treatment of Clostridioides difficile Infection in Adult Patients: An Update on Results from Randomized Controlled Trials.

In recently updated international guidelines, fidaxomicin is preferentially recommended as first-line treatment over vancomycin both for the first episode of CDI and for rCDI, based on the results of different randomized controlled trials (RCTs). Although noninferiority was the rule in phase-3 RCTs with regard to the primary endpoint of clinical cure, for shaping these recommendations, particular attention was devoted to the improved global cure and reduced risk of recurrent CDI (rCDI) observed with fidaxomicin compared to vancomycin in RCTs. Overall, while the major driver of choice should remain the global benefit for the patient, consideration of available resources should be necessarily weighed in the balance, since fidaxomicin still remains more costly than vancomycin. Against this background, precisely stratifying risk groups for rCDI will represent a crucial research trajectory of future real-life studies on the treatment of first CDI episodes. In the current narrative review, we discuss the updated evidence from RCTs on the efficacy of fidaxomicin for the treatment of either the first CDI episode or rCDI, which eventually supports its positioning within current treatment algorithms and guidelines.

Recurrent Clostridioides difficile infection worsens anxiety-related patient-reported quality of life

BackgroundClostridioides difficile infection (CDI) is associated with high recurrence rates impacting health-related quality of life (HrQOL). However, patient-reported data are lacking particularly in the outpatient setting. We assessed changes in HrQOL over time in patients treated with bezlotoxumab at US infusion centers and determined clinical factors associated with HrQOL changes.MethodsThe HrQOL survey was conducted in adult patients with CDI, who received bezlotoxumab in 25 US outpatient infusion centers. The survey was adapted from the Cdiff32 instrument to assess anxiety-related changes to HrQOL and completed on the day of infusion (baseline) and at 90 days post bezlotoxumab (follow-up). Demographics, disease history, CDI risk factors, and recurrence of CDI (rCDI) at 90-day follow-up were collected. Changes in HrQOL scores were calculated and outcomes assessed using a multivariable linear regression model with P < 0.05 defined as statistically significant.ResultsA total of 144 patients (mean age: 68 ± 15 years, 63% female, median Charlson index: 4, 15.9% rCDI) were included. The overall mean baseline and follow-up HrQOL scores were 26.4 ± 11.5 and 56.4 ± 25.0, respectively. At follow-up, this score was significantly higher for patients who had primary CDI (34.5 ± 21.7) compared to those with multiple rCDI (24.7 ± 21.0; P = 0.039). The mean HrQOL change at follow-up was significantly higher for patients without rCDI (34.1 ± 28.8 increase) compared to patients with rCDI (6.7 ± 19.5 increase; P < 0.001), indicating improvement in anxiety.ConclusionsUsing the Cdiff32 instrument, we demonstrated that HrQOL worsened significantly in patients with further rCDI. These findings support the use of Cdiff32 in assessing CDI-related humanistic outcomes.

Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study

BackgroundClostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared...

Risk factors and clinical outcomes for Clostridioides difficile infections in a case control study at a large cancer referral center in Mexico

IntroductionClostridioides difficile infection (CDI) is recognized as the leading cause of nosocomial diarrhea. This study describes CDI's clinical characteristics, risk factors, and outcomes in the cancer population. MethodsWe conducted a case-control study on cancer patients from 2015-2018 at the Instituto Nacional de Cancerologia in Mexico. CDI case was defined as diarrhea episode and positive polymerase chain reaction (PCR) for toxigenic strains. Controls were cancer diagnosis-matched patients with diarrhea and negative PCR. Healthcare Facility-Onset (HO-CDI) and Community-Onset, Healthcare Facility-Associated (CO-HCFA-CDI) rates were calculated. For assessing associations, univariate and multivariate logistic regression analyses were conducted. ResultsWe included 148 CDI cases and 148 controls. The CDI rate was 4.1 per 10,000 patient-days and 2.1 per 1,000 patient admissions for HO-CDI and CO-HCFA-CDI episodes, respectively. Clinical characteristics associated with CDI were fever, abdominal pain, and ≥4 episodes of diarrhea/24h. Previous use of proton pump inhibitors (P=.003), fluoroquinolones (P=.016), and cephalosporins (P=.026) increased the risk for CDI acquisition, while higher age (P=.022) and male gender (P=.015) were related to severe episodes. Thirty-day all-cause mortality was higher among CDI patients (18%) than controls (9%). ConclusionThe CDI rate was lower compared to other series. The incidence of CO-HCFA-CDI episodes increased, and HO-CDI cases decreased from 2016 to 2018. Risk factors for acquisition and severe infection were similar to those reported in non-cancer populations.

Association between duration of antipseudomonal beta-lactam therapy and Clostridioides difficile infections in monomicrobial Enterobacterales bloodstream infections at an academic medical center

To evaluate the effects early de-escalation of antipseudomonal β-lactam (APBL) on 90-day CDI risk in Enterobacterales bloodstream infections (BSIs). Retrospective cohort analysis. An academic medical center in South Carolina. We included patients aged >18 years with monomicrobial BSIs with Enterobacterales who received APBL between July 1, 2015, and June 30, 2020. Rates of CDI were compared between patients who received an APBL for >72 hours and <72 hours, followed by comparison between formulary APBLs utilized. In total, 447 patients were included; 292 and 155 patients received APBL for < 72 hours and > 72 hours, respectively. The incidences of CDI for <72 hours compared to >72 hours were 2.4% and 6.5%, respectively (unadjusted hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.03-7.10; P = .04). This difference was not statistically significant in the adjusted model (HR, 2.66; 95% CI, 0.97-7.31; P = .06). Meropenem was associated with an increased risk of CDI when compared with all other formulary APBLs: 4 (26.7%) of 15 versus 13 (3.0%) of 432 (P < .001). Utilization of an APBL for >72 hours was associated with a statistically significant increase in the incidence of CDI in an unadjusted model and with a numerically higher CDI incidence in the adjusted model. Meropenem was the formulary APBL that carried the highest risk of CDI. The results of this study provide further evidence supporting active antimicrobial stewardship to reduce unnecessary broad-spectrum antibiotics in the effort to alleviate the burden that CDI imposes on the healthcare system.

Beyond Pain Relief: Is Opioids Use Safe in Clostridioides Difficile Infection?

Factors that increase the risk of CDI include malignancy, antibiotic usage, and increased number of comorbidities, chronic kidney disease, inflammatory bowel disease, cirrhosis, gastrointestinal surgery, proton pump inhibitors, histamine h2-receptor antagonists, and steroid use. Fortunately, affected by a decrease in health care associated infections, the incidence of CDI declined (154.9 to 143.6 per 100,000 persons) between 2011 and 2017.

745. Evaluation of a Pharmacist-driven Risk Factor Tool for the Prevention of Hospital-onset Clostridium difficile Infection in a Community Hospital

Abstract Background Clostridium difficile infection (CDI) is the most frequently reported nosocomial infection and is the major cause of healthcare and antibiotic associated diarrhea. Guideline recommended preventative strategies include antibiotic stewardship, hand hygiene, barrier precautions, and disinfection of environmental spaces to reduce the risk of hospital onset CDI (HO-CDI); however, there is no standardized scoring method to tactically detect high-risk patients in order to prevent HO-CDI. The objective of this study was to implement a risk stratification procedure for a pharmacist to prospectively identify high-risk patients and make early interventions to prevent the incidence of HO-CDI. Methods In this single center, ambidirectional cohort study, patients who acquired HO-CDI from January 2019 to June 2020 were identified and evaluated to determine which modifiable risk factors were most prominent. A pharmacist prospectively screened patients who were admitted from October 2020 to February 2021 using a web-based screening tool to detect high-risk patients based on the previously identified risk factors. An interdisciplinary approach was used to make early interventions for high-risk patients such as discontinuation or de-escalation of antibiotics, discontinuation of gastric acid suppression, and early CDI testing before 72 hours of admission. The primary outcome was incidence of HO-CDI per 10,000 patient days and secondary outcomes were length of hospital stay and duration of non-CDI antibiotic therapy. Appropriate statistical tests were used to measure significance. Results The primary outcome of HO-CDI cases per 10,000 patient days occurred at a median rate of 3.95 (IQR 3.38 – 6.30) in the retrospective cohort versus 2.15 (IQR 1.68 – 3.04) in the prospective cohort [p &amp;lt; 0.0125]. There were no significant differences in length of non-CDI antibiotic therapy or length of hospital stay. Baseline Characteristics Primary Outcome Secondary Outcomes Conclusion In patients at high-risk of developing HO-CDI, pharmacist intervention resulted in a reduced rate of HO-CDI cases per 10,000 patient days. Disclosures All Authors: No reported disclosures

18. Global Surveillance of Clostridioides difficile Demonstrates High Prevalence in Non-Healthcare Settings

Background Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing organism that is the leading cause of healthcare-associated infections. However, past studies have isolated C. difficile spores from the community, suggesting an environmental reservoir that may play a role in transmission. This study aimed to examine the prevalence and strain types of C. difficile isolated from the United States (US) and internationally.MethodsFrom 2014 to 2017, environmental swabs were collected from public areas, healthcare settings, and shoe soles. Samples were considered positive for C. difficile following growth on CCFA plates and confirmatory PCR testing for toxin genes and fluorescent PCR ribotyping (RT). The rate of C. difficile positivity and associated RT distribution were compared between settings, including shoe soles which were investigated for their potential role in environmental transmission.ResultsA total of 11,986 unique isolates were obtained primarily from the US (n=11,002; 92%) in addition to 11 other countries including Taiwan (n=200) and India (n=187). Samples were categorized as being from outdoor environments (n=2,992), private residences (n=2,772), shoe soles (n=1,420), public buildings (n=1,104) or acute care settings (n=3,698). Worldwide C. difficile sample positivity was 26% and was similar between US and non-US sampling sites. In the US, private residences (26.2%) and outdoor environments (24.1%) had the highest positivity rate compared to public buildings (17.2%). In a Texas sub-analysis (n=8,571), positivity rates were highest from outdoor samples (27%) and were similar between private residences (24%) and healthcare buildings (24%). The most prevalent RTs overall were F014-020 (16.4%), F106 (14.9%), and FP310 (11%). Shoe soles had the highest positivity rate (45%) with similar RT distribution between shoe soles and environmental samples.ConclusionUsing a worldwide sample, 26% of environmental samples tested positive for toxigenic C. difficile strains from healthcare and non-healthcare sites. Community stewardship efforts will be needed to reduce the risk of CDI in vulnerable patients. Shoe sole sampling may be an ideal surveillance tool to test for emerging epidemic strains.Disclosures Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support)

Add-on interventions for the prevention of recurrent Clostridioides Difficile infection: A systematic review and network meta-analysis

ObjectivesWe aimed to assess the comparative efficacy and safety of adjunctive interventions for the prevention of Clostridioides difficile recurrence. MethodsWe searched Medline, Embase, CENTRAL, and clinicaltrials.gov up to May 2021. We included randomized controlled trials comparing interventions added to antibiotic therapy for prevention of CDI recurrence, to placebo or each other. Efficacy outcomes were CDI and diarrhea recurrence. Safety outcomes included the incidence of any adverse event (AE), serious AEs, and discontinuation due to AEs. We performed random-effects network meta-analysis. We ranked interventions based on SUCRA (surface under the cumulative ranking curve) probabilities. We assessed confidence in estimates utilizing the CINeMA (Confidence in Network Meta-Analysis) framework. ResultsFifteen trials (3909 patients) assessed 9 interventions. Oligofructose (OR 0.17; 95% CI, 0.07 to 0.46), NTCD-M3 (OR 0.29; 95% CI, 0.12 to 0.68), rifaximin (OR 0.47; 95% CI, 0.24 to 0.93), RBX2660 (OR 0.47; 95% CI, 0.22 to 0.99), the combination bezlotoxumab/actoxumab (OR 0.47; 95% CI, 0.37 to 0.60), and bezlotoxumab (OR, 0.53; 95% CI, 0.42 to 0.68) were associated with lower incidence of CDI recurrence than placebo (moderate confidence). Oligofructose was ranked highest, however data for oligofructose were derived solely from one small trial. Probiotics, actoxumab and SER-109 were not superior to placebo (low confidence). Probiotics were not well tolerated (low confidence) and actoxumab showed high rates of serious AEs (moderate confidence). ConclusionAdd-on treatment with oligofructose, NTCD-M3 spores, rifaximin, RBX2660, and bezlotoxumab likely reduces the risk of CDI. Evidence on probiotics and SER-109 are uncertain, thus adequately powered trials are warranted.

Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection.

ABSTRACTClostridioides difficile is a noteworthy pathogen in patients with inflammatory bowel disease (IBD). Patients with IBD who develop concurrent C. difficile infection (CDI) experience increased morbidity and mortality. IBD is associated with intestinal inflammation and alterations of the gut microbiota, both of which can diminish colonization resistance to C. difficile. Here, we describe the development of a mouse model to explore the role that IBD-induced changes of the gut microbiome play in susceptibility to C. difficile. Helicobacter hepaticus, a normal member of the mouse gut microbiota, triggers pathological inflammation in the distal intestine akin to human IBD in mice that lack intact interleukin 10 (IL-10) signaling. We demonstrate that mice with H. hepaticus-induced IBD were susceptible to C. difficile colonization in the absence of other perturbations, such as antibiotic treatment. Concomitant IBD and CDI were associated with significantly worse disease than observed in animals with colitis alone. Development of IBD resulted in a distinct intestinal microbiota community compared to that of non-IBD controls. Inflammation played a critical role in the susceptibility of animals with IBD to C. difficile colonization, as mice colonized with an isogenic mutant of H. hepaticus that triggers an attenuated intestinal inflammation maintained full colonization resistance. These studies with a novel mouse model of IBD and CDI emphasize the importance of host responses and alterations of the gut microbiota in susceptibility to C. difficile colonization and infection in the setting of IBD.

Decreasing ICU-associated Clostridioides difficile infection through fluoroquinolone restriction, the FIRST trial: a study protocol

IntroductionClostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the USA, having high incidence in intensive care units (ICU). Antibiotic use increases risk of CDI, with...