Prevention Of Clostridioides Difficile Infection Research Articles

Live Biotherapeutic Products for the Prevention of Recurrent Clostridioides difficile Infection.

To review the efficacy, safety, and role of live biotherapeutic products (LBPs) in the prevention of recurrent Clostridioides difficile infection (rCDI). A literature search was performed using PubMed and Google Scholar (through February 2024) with search terms RBX2660, SER-109, and fecal microbiota. Other resources included abstracts presented at recent conferences, national clinical practice guidelines, and manufacturers' websites. All relevant studies, trial updates, conference abstracts, and guidelines in the English language were included. Two LBPs were recently approved by the Food and Drug Administration for the prevention of recurrence in adults following antibiotic treatment for rCDI. Fecal microbiota, live-jslm is administered rectally as a retention enema, whereas fecal microbiota spores, live-brpk is given orally after bowel preparation. Several phase 2 and phase 3 clinical trials have established the safety and efficacy of these LBPs in reducing rates of rCDI compared with placebo. Patients with severe immunosuppression and those with inflammatory bowel disease were largely excluded from these trials. Live biotherapeutic products offer a similar mechanism to conventional fecal microbiota transplant (FMT) in preventing rCDI through microbiota restoration. The primary advantages of LBPs over FMT are their standardized composition and donor stool screening processes for transmissible pathogens. Bezlotoxumab is also available for the prevention of Clostridioides difficile infection; however, there are no clinical data available to compare the efficacy of LBPs with bezlotoxumab, and the benefit of simultaneous use of these preventative therapies is unclear. Live biotherapeutic products provide a safe and effective option for the prevention of rCDI and represent an improvement over conventional FMT. Additional studies are needed to further determine their place in therapy relative to bezlotoxumab and in the setting of immunosuppression and inflammatory bowel disease.

Incidence of Clostridium difficile in Patients with Antibiotic Associated Diarrhea

Background: This study was performed to determine the magnitude of Clostridioides difficile infection (CDI) in a tertiary care hospital in patients with antibiotic associated diarrhea (AAD) and to study the risk factors associated with this disease.
 Methods: A descriptive study was conducted in the department of Microbiology in a tertiary care hospital during December 2019 to May 2021. Stool samples were collected from patients with signs and symptoms of AAD who had been consuming antibiotic or anticancer drugs durng six weeks before the sampling. The samples were subjected to C. difficile glutamate dehydrogenase (GDH) enzyme and CD toxin A & B detection by Enzyme Linked Fluorescent Assay (ELFA). Patient’s demographic features and clinical details were noted and statistically correlated with the test results
 Results: Among the total 70 samples tested 20 (28%) were positive for GDH alone and 12 (17%) were positive for both GDH and CD toxin A and B. Fluoroquinolones was a significant risk factor in the study. Sepsis and colitis was found to have significant association with C.difficile infection in our study. The crude mortality rate was 17%.
 Conclusion: Prompt and precise diagnosis and knowledge about the risk factors of CDI helps in effective management and prevention of CDI.

SER-109 (VOWST™): A Review in the Prevention of Recurrent Clostridioides difficile Infection.

SER-109 (VOWST™; fecal microbiota spores, live-brpk) is a live biotherapeutic product indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in patients 18years of age and older following standard of care (SOC) antibacterial treatment for recurrent CDI. It is a purified bacterial spore suspension sourced from healthy donors. As the first oral faecal microbiota product approved for prevention of recurrent CDI, SER-109 is administered as four capsules once daily for three consecutive days. In a well-designed, placebo-controlled, phaseIII trial (ECOSPORIII), SER-109 significantly reduced the risk of recurrent CDI at 8weeks post-treatment, with a durable response seen at 6months post-treatment. Treatment with SER-109 was also associated with rapid and steady improvement in health-related quality of life compared with placebo. SER-109 was generally well tolerated, with a safety profile similar to that of placebo. The most common adverse events were of mild to moderate severity and generally gastrointestinal in nature. Thus, with the convenience of oral administration and lack of necessity for cold storage, SER-109 is a valuable option for preventing further CDI recurrence in adults following antibacterial treatment for recurrent CDI.

The Role of Probiotics in the Prevention of Clostridioides difficile Infection in Patients with Chronic Kidney Disease.

In patients suffering from chronic kidney disease (CKD), substantial unfavourable alterations in the intestinal microbiota composition, i.e., dysbiosis, have been noted. The main causes of such dysbiosis among others are insufficient dietary fibre content in the diet, fluid restrictions, medications used, and physical activity limitation. One clinically important consequence of dysbiosis in CKD patients is high risk of Clostridioides difficile infection (CDI). In observational studies, it was found that CDI is more frequent in CKD patients than in the general population. This appears to be related to high hospitalization rate and more often antibiotic therapy use, leading up to the occurrence of dysbiosis. Therefore, the use of probiotics in CKD patients may avert changes in the intestinal microbiota, which is the major risk factor of CDI. The aim of this review paper is to summarize the actual knowledge concerning the use of probiotics in CDI prevention in CKD patients in the context of CDI prevention in the general population.

Rethinking Clostridioides difficile infection (CDI) surveillance definitions based on changing healthcare utilisation and a more realistic incubation period: reviewing data from a tertiary-referral hospital, Ireland, 2012 to 2021.

BackgroundCommunity-associated Clostridioides difficile infections (CA-CDI) have increased worldwide. Patients with CDI-related symptoms occurring < 48 hours after hospitalisation and no inpatient stay 12 weeks prior are classified as CA-CDI, regardless of hospital day attendances 3 months before CDI onset. Healthcare-associated (HA) CDIs include those with symptom onset ≥ 48 hours post hospitalisation.AimTo consider an incubation period more reflective of CDI, and changing healthcare utilisation, we measured how varying surveillance specifications to categorise patients according to their CDI origin resulted in changes in patients' distribution among CDI origin categories.MethodsNew CDI cases between 2012-2021 from our hospital were reviewed. For patients with CA-CDI, hospital day attendances in the 3 months prior were recorded. CA-CDI patients with hospital day attendances and recently discharged CDI patients (RD-CDI; CDI onset 4-12 weeks after discharge) were combined into a new 'healthcare-exposure' category (HE-CDI). Time from hospitalisation to disease onset was varied and the midpoint between optimal and balanced cut-offs was used instead of 48 hours to categorise HA-CDI.ResultsOf 1,047 patients, 801 (76%) were HA-CDI, 205 (20%) CA-CDI and 41 (4%) were RD-CDI. Of the CA-CDI cohort, 45 (22%) met recent HE-CDI criteria and, when reassigned, reduced CA-CDI to 15%. Sensitivity analysis indicated a day 4 cut-off for assigning HA-CDI. Applying this led to 46 HA-CDI reassigned as CA-CDI. Applying both HE and day 4 criteria led to 72% HA-CDI, 20% CA-CDI, and 8% HE-CDI (previously RD-CDI).ConclusionCDI surveillance specifications reflecting healthcare exposure and an incubation period more characteristic of C. difficile may improve targeted CDI prevention interventions.

The Need for European Surveillance of CDI.

Since the turn of the millennium, the epidemiology of Clostridioides difficile infection (CDI) has continued to challenge. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and standardised surveillance systems. However, a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has led to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country CDI surveillance program and optimised diagnostic strategies are required has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks led to the development of the European surveillance protocol and an over-arching long-term CDI surveillance strategy for 2014-2020, which has been followed by the development of surveillance systems in at least 20 European countries. However, surveillance activities in individual countries have slowed during the COVID-19 pandemic as resources were diverted to the global health crisis. A renewed and strengthened focus on CDI surveillance and prevention is therefore urgently needed post COVID-19.

706. An Ad Hoc Subgroup Analysis of a Phase 3, Open-Label Study Indicates Efficacy and Safety of Fecal Microbiota, Live-jslm in Participants With Recurrent Clostridioides difficile Infection and Renal Impairment

Abstract Background Patients with renal comorbidity are at risk of severe Clostridioides difficile infection (CDI) and recurrence. Fecal microbiota, live-jslm (REBYOTA™, abbreviated here as RBL, previously known as RBX2660) is the first FDA-approved, microbiota-based live biotherapeutic for the prevention of recurrent CDI (rCDI) in adults following antibiotic treatment for rCDI. An ad hoc subgroup analysis of PUNCH CD3-OLS (NCT03931941), an ongoing, open-label, phase 3 trial evaluating the efficacy and safety of RBL, assessed outcomes in participants with renal comorbidity. Methods PUNCH CD3-OLS participants were ≥ 18 years old with medically documented rCDI, including first recurrence determined by the treating physician, and assessed with standard-of-care (SOC) diagnostic methods. After SOC antibiotics, participants received a single dose of rectally administered RBL. Treatment success was defined as remaining recurrence free for 8 weeks after treatment. Treatment-emergent adverse events (TEAEs) through 6 months of treatment were reported. Participants with renal comorbidity were identified from the medical history dictionary-derived terms in the modified intent-to-treat (mITT) population. Results Within the mITT population, 98 of 402 participants with adjudicated outcomes had renal comorbidity, including chronic kidney disease (n=29) and end-stage renal failure (n=5). Of participants with renal comorbidity, 50% had Charlson Comorbidity Index scores of ≥ 5, versus 18% of participants without renal comorbidity. Treatment success was achieved by 66% (65/98) and 77% (235/304) of participants with and without renal comorbidity, respectively. TEAEs occurred in 71% (n=70) of participants with renal comorbidity and 64% (n=194) of participants without renal comorbidity. In both groups, most TEAEs were moderate in severity and related to preexisting conditions. Serious TEAEs were reported by 16% (n=16) and 8% (n=24) of participants with and without renal comorbidity, respectively. The most commonly reported serious TEAE was CDI recurrence, occurring in 3.1% (n=3) and 1.6% (n=5) of participants with and without renal comorbidity, respectively. Conclusion RBL treatment success and TEAE incidence were numerically comparable for those with and without renal comorbidity. Disclosures Monika Fischer, MD, Ferring Pharmaceuticals Inc.: Advisor/Consultant|Rebiotix Inc., a Ferring Company: Board Member|Seres Pharmaceuticals: Advisor/Consultant Joan Thul, BA, Ferring Pharmaceuticals Inc.: Employee Beth Guthmueller, AS, Rebiotix Inc., a Ferring Company: Employee Christian Sandrock, MD, Allergan: Advisor/Consultant|National Institutes of Health: Grant/Research Support|Shionogi: Advisor/Consultant|The Health Resources &amp; Services Administration: Grant/Research Support Nicholas Van Hise, PharmD, Ferring Pharmaceuticals Inc.: Advisor/Consultant|Ferring Pharmaceuticals Inc.: investigator Glenn S. Tillotson, PhD, Dynavax: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Peggy Lillis Foundation: Honoraria|Spero Therapeutics: Advisor/Consultant

Host Immune Responses to Clostridioides difficile Infection and Potential Novel Therapeutic Approaches.

Clostridioides difficile infection (CDI) is a leading nosocomial infection, posing a substantial public health challenge within the United States and globally. CDI typically occurs in hospitalized elderly patients who have been administered antibiotics; however, there has been a rise in the occurrence of CDI in the community among young adults who have not been exposed to antibiotics. C. difficile releases toxins, which damage large intestinal epithelium, leading to toxic megacolon, sepsis, and even death. Unfortunately, existing antibiotic therapies do not always prevent these consequences, with up to one-third of treated patients experiencing a recurrence of the infection. Host factors play a crucial role in the pathogenesis of CDI, and accumulating evidence shows that modulation of host immune responses may potentially alter the disease outcome. In this review, we provide an overview of our current knowledge regarding the role of innate and adaptive immune responses on CDI outcomes. Moreover, we present a summary of non-antibiotic microbiome-based therapies that can effectively influence host immune responses, along with immunization strategies that are intended to tackle both the treatment and prevention of CDI.

Progress on mechanisms of antibiotic resistance in Clostridioides difficile.

Clostridioides difficile (CD) is one of the most common pathogens causing health-care-associated infectious diarrhea and is listed by the U.S. Centers for Disease Control and Prevention as an urgent antibiotic resistance (AR) threat. Many resistance genes can be transferred between different CD strains present in the clinical setting, community, and environment. The antimicrobial resistance (AMR) of CD continues to evolve with the emergence and acquisition of new drug resistance mechanisms. CD has developed diverse drug resistance mechanisms, such as drug alteration, modification of the target site, and extrusion of drugs via efflux pumps. Researches have provided comprehensive knowledge about resistance mechanisms of macrolides and quinolones in CD. However, the mechanisms of resistance for metronidazole, vancomycin, and other therapeutic antibiotics against Clostridioides difficile infection (CDI) are only beginning to be elucidated. Some previously unfound mechanisms, such as plasmid-mediated drug resistance in CD, may also play an important role. In this review, we summarize the research progress on drug resistance mechanisms of CD with antimicrobial drugs already used clinically, such as metronidazole, vancomycin, and fidaxomicin, thereby providing the references for the clinical treatment and prevention of CDI, as well as the development of new antibacterial drugs and detection kits for drug resistant bacteria.

Clostridioides difficile infection in a skilled nursing facility (SNF): cost savings of an automated, standardized probiotic antimicrobial stewardship programme (ASP) policy.

With multiple comorbidities and frequent exposures to antibiotics, patients in skilled nursing facilities (SNFs) are much more vulnerable to healthcare-acquired infections. We conducted a quality-improvement, retrospective analysis of all patients with Clostridioides difficile infection (CDI) from 2009 to 2021 at an SNF. Probiotics were initially added to a bundle of antimicrobial stewardship programme (ASP) CDI prevention strategies. Formulations and durations of probiotics were standardized for both oral and enteral administration. To reach all eligible patients, an ASP probiotic policy provided probiotics with every antibiotic course. To assess the value of providing probiotic therapy to SNF patients at risk for CDI. Patients receiving oral or enteral feeding with antibiotics ordered were eligible to receive probiotics. The incremental cost of CDI prevention, treatment and related care were calculated and compared for each phase of probiotic policy change and feeding type. ASP records for the oral probiotic and level of treatment were used in modelling the cost-effectiveness. From quality improvement initiatives aimed at preventing facility-onset (FO) CDI, to ASP policies, probiotic formulations and delegation of ordering authority, the days of acute care treatment required was significantly reduced over the different phases of implementation [152 to 48, OR = 0.22 (0.16-0.31) to 4, OR = 0.08 (0.03-0.23)] after reducing total CDI from 5.8 to 0.3 cases per 10 000 patient-days. The annual cost of oral probiotics increased from $6019 to $14 652 but the modelled net annual savings for the facility was $72 544-$154 085. With optimization, the use of probiotics for CDI prevention at an SNF was safe, efficacious and cost-effective.

Role of probiotics in preventing Clostridioides difficile infection in older adults: an integrative review.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. This infection can particularly affect older adults, the most susceptible to CDI. Currently, the standard therapeutic measure is antibiotic therapy, which in turn increases the risk of recurrence of the infection by its collateral damage to the patient's microbiota. Probiotics are live microorganisms capable of maintaining balance in the intestinal microbiota. This study aims to perform an integrative review of the protective benefit of probiotics in CDI and diarrhea associated with C. difficile. The PubMed, Scopus, and Web of Science databases, the 10-year time cutoff, and the Prism Flow diagram were used for data collection. We observed no consensus among the studies; however, three of the seven evaluated studies demonstrated that the use of probiotics in older adults could contribute to reducing the incidence of hospital-onset CDI. We also found that the studies evaluated a wide variety of microorganisms, particularly Saccharomyces boulardii, associated with beneficial effects. More research is needed to understand the successful use of probiotics in the prevention of CDI in hospitalized older adults receiving antibiotics.

Consider new therapies for the treatment and prevention of Clostridioides difficile infection

Consider new therapies for the treatment and prevention of Clostridioides difficile infection

Double-Blind, Placebo-Controlled Study of Bezlotoxumab in Children Receiving Antibacterial Treatment for Clostridioides difficile Infection (MODIFY III).

Therapies to prevent recurrence of Clostridioides difficile infection (CDI) in pediatric patients are needed. Bezlotoxumab is a fully human monoclonal antibody approved for prevention of recurrent CDI in adults. We assessed the pharmacokinetics, safety, tolerability, and efficacy of bezlotoxumab in pediatric patients. MODIFY III was a multicenter, double-blind, placebo-controlled study of bezlotoxumab in children (1 to <18 years) receiving antibacterial treatment for CDI. Participants were randomized 3:1 to receive a single infusion of bezlotoxumab (10 mg/kg) or placebo and were stratified by age at randomization (cohort 1: 12 to <18 years, cohort 2: 1 to <12 years). The primary objective was to characterize bezlotoxumab pharmacokinetics to support dose selection for pediatric patients; the primary endpoint was the area under the bezlotoxumab serum concentration-time curve (AUC0-inf). Safety, tolerability, and efficacy were monitored for 12 weeks post-infusion. A total of 148 participants were randomized and 143 were treated: 107 with bezlotoxumab and 36 with placebo (cohort 1 n = 60, cohort 2 n = 83; median age 9.0 years); 52.4% of participants were male and 80.4% were white. Geometric mean ratios (90% CI) for bezlotoxumab AUC0-inf were 1.06 (0.95, 1.18) and 0.82 (0.75, 0.89) h * μg/mL for cohorts 1 and 2, respectively. Bezlotoxumab 10 mg/kg was generally well-tolerated with an adverse event profile similar to placebo, including no treatment discontinuations due to adverse events. CDI recurrence was low and comparable for bezlotoxumab (11.2%) and placebo (14.7%). The results of this study support the bezlotoxumab dose of 10 mg/kg for pediatric patients. NCT03182907 at ClinicalTrials.gov.

Investigating the Correlation Between Clostridioides difficile Infection and Vitamin D Deficiency.

Clostridioides difficile infection (CDI) is the most common healthcare-associated infection in the US. Symptoms include watery diarrhea, nausea, and anorexia and it can present with leukocytosis on laboratory evaluation. Treatment is based on disease severity and recurrence. Despite antibioticusage being the highest risk factor for infection, they are also the first-line treatment for initial CDI. Prevention of CDI mostly involves good hand hygiene, antibiotic stewardship, and appropriate precautions when interacting with infected individuals. Vitamin D deficiency (VDD) has been linked to CDI, however, there is limited insight into the correlation between both states. Our aim was to further investigate the potential link between VDD and CDI. Data were obtained from the National Inpatient Sample (NIS) from 2016 to 2019. Patients with CDI were identified and stratified based on a diagnosis of VDD. Primary outcomes were mortality, CDI recurrence, ileus, toxic megacolon, perforation, and colectomy. Chi-squared and independent t-tests were performed to assess categorical and continuous data, respectively. Multiple logistic regression was used to control for confounders. Patients with VDD had higher rates of CDI recurrence (17.4% versus 14.7%,p<0.05), but lower rates of mortality (3.1% versus 6.1%, p<0.05). Differences in rates of ileus, toxic megacolon, perforation, and colectomy were statistically insignificant. Length of stay was higher in the VDD group (10.38 days versus 9.83 days). Total charges were lower in the VDD group ($93,935.85 versus $102,527.9). CDI patients with comorbid VDD are at higher risk for the recurrence of CDI. This is likely due to the role of vitamin D in the expression of intestinal epithelial antimicrobial peptides, macrophage activation, and maintenance of tight junctions between gut epithelial cells. Furthermore, vitamin D plays a role in maintaining a healthy gut microbiome. Alternatively, deficiency results in poor gut health and detrimental changes to the gut microbiome. In effect, VDD promotes the proliferation of C. difficile within the large colon, resulting in an increased predisposition for CDI.

VE303, a Defined Bacterial Consortium, for Prevention of Recurrent Clostridioides difficile Infection

The effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown. To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial. Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the US and Canada. The study included 79 participants aged 18 years or older who were diagnosed with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence (defined as aged ≥75 years or ≥65 years with ≥1 risk factors: creatinine clearance <60 mL/min/1.73 m2, proton pump inhibitor use, remote [>6 months earlier] CDI history). Participants were randomly assigned to high-dose VE303 (8.0 × 109 colony-forming units [CFUs]) (n = 30), low-dose VE303 (1.6 × 109 CFUs) (n = 27), or placebo capsules (n = 22) orally once daily for 14 days. The primary efficacy end point was the proportion of participants with CDI recurrence at 8 weeks using a combined clinical and laboratory definition. The primary efficacy end point was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence: (1) diarrhea consistent with CDI plus a toxin-positive stool sample; (2) diarrhea consistent with CDI plus a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample; and (3) diarrhea consistent with CDI plus laboratory confirmation or (in the absence of a stool sample) treatment with a CDI-targeted antibiotic. Baseline characteristics were similar across the high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups. The participants' median age was 63.5 years (range, 24-96); 70.5% were female; and 1.3% were Asian, 1.3% Black, 2.6% Hispanic, and 96.2% White. CDI recurrence rates through week 8 (using the efficacy analysis 3 definition) were 13.8% (4/29) for high-dose VE303, 37.0% (10/27) for low-dose VE303, and 45.5% (10/22) for placebo (P = .006, high-dose VE303 vs placebo). Among adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo. A larger, phase 3 study is needed to confirm these findings. ClinicalTrials.gov Identifier: NCT03788434.

CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models.

Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 μg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.

Frontline perspectives of C. difficile infection prevention practice implementation within veterans affairs health care facilities: A qualitative study

In 2012, the Veteran's Affairs (VA) Multidrug-Resistant Organism (MDRO) Program Office launched a national Clostridioides difficile Infection (CDI) Prevention Initiative to address CDI as the most common cause of healthcare associated infections, mandating use of a VA CDI Bundle of prevention practices in inpatient facilities. We draw upon frontline worker perspectives to explore work system barriers and facilitators to the sustained implementation of the VA CDI Bundle using the Systems Engineering Initiative for Patient Safety (SEIPS) framework. We interviewed 29 key stakeholders at 4 participating sites between October 2019-July 2021. Participants included infection prevention and control (IPC) leaders, nurses, physicians, and environmental management staff. Interviews were analyzed to identify themes and perceptions of facilitators and barriers to CDI prevention. IPC leadership was most likely to know of the specific VA CDI Bundle components. Other participants demonstrated general knowledge of CDI prevention practices, with role-based variation in the depth of awareness of specific practices. Facilitators included leadership support, mandated CDI training and prevention practices, and readily available training from multiple sources. Barriers included limits to communication about facility or unit-level CDI rates, ambiguous communications about CDI prevention practice updates and VA mandates, and role-hierarchies that may limit team members' clinical contributions. Recommendations include improving centrally-mandated clarity about and standardization of CDI prevention policies, including testing. Regular IPC training updates for all clinical stakeholders are also recommended. A work system analysis using SEIPS identified barriers and facilitators to CDI prevention practices that could be addressed both nationally at the system level and locally at the facility level, specifically in the areas of communication and coordination.

Antimicrobial Activity of Tannic Acid In Vitro and Its Protective Effect on Mice against Clostridioides difficile.

Clostridioides difficile infection (CDI), recurrently reported as an urgent threat owing to its increased prevalence and mortality, has attracted significant attention. As the use of antibiotics to treat CDI has many limitations, such as high recurrence rate, the need to actively seek and develop other drugs that can effectively treat CDI with fewer side effects has become a key issue in CDI prevention and treatment. This study aimed to evaluate the inhibitory effect of Galla chinensis (GC) and its main component, tannic acid (TA), against C. difficile in vitro and its therapeutic effect on CDI in vivo. When GC and TA concentrations were 250 and 64 mg/L, respectively, the cumulative antibacterial rate against C. difficile reached 100%. The sub-MIC of TA significantly inhibited C. difficile sporulation, toxin production, and biofilm formation in vitro. Compared with the CDI control group, TA-treated mice lost less weight and presented a significantly improved survival rate. TA significantly reduced the number of spores in feces, decreased serum TcdA level, and increased serum interleukin 10 (IL-10). Based on the inhibitory effect of TA on C. difficile in vitro and its therapeutic effect on the CDI mouse model, we consider TA as a potentially effective drug for treating CDI. IMPORTANCE Clostridioides difficile is one of the major pathogens to cause antibiotic-associated diarrhea. Although antibiotic treatment is still the most commonly used and effective treatment for CDI, the destruction of indigenous intestinal microbiota by antibiotics is the main reason for the high CDI recurrence rate of about 20%, which is increasing every year. Moreover, the growing problem of drug resistance has also become a major hidden danger in antibiotic treatment. GC has been used to treat diarrhea in traditional Chinese medicine. In the present study, we evaluated the inhibitory effect of TA, the main component of GC, on dissemination and pathogenic physiological functions of C. difficile in vitro, as well as its therapeutic efficacy in a CDI model. Overall, TA is considered to be a potentially effective drug for CDI treatment.

213. Prophylactic oral vancomycin for Clostridioides difficile in allogeneic hematopoietic stem cell transplant recipients

Abstract Background Allogeneic hematopoietic stem cell transplant (alloHSCT) recipients are at substantial risk for Clostridioides difficile infection (CDI) due to prolonged hospitalization and alteration of the intestinal mucosa and gut microbiota from conditioning regimens, antimicrobials, and immunosuppressants. CDI in alloHSCT recipients has also been associated with higher rates of acute graft versus host disease (aGVHD). Review of the literature revealed that three institutions have published studies demonstrating oral vancomycin prophylaxis prevents CDI. However, more studies are needed to evaluate the impact of prophylaxis on CDI incidence, resistant infections, and other transplant-related outcomes. Methods We conducted a retrospective review to compare the effectiveness of prophylactic oral vancomycin versus no prophylaxis in 40 alloHSCT recipients in the prevention of CDI at our institution. The prophylactic intervention was initiated June 2020, and 20 patients have undergone alloHSCT as of April 2022. Patients received twice daily oral vancomycin starting the day of admission for transplant until discharge. The prophylaxis group was compared to a control group of 20 consecutive alloHSCT recipients prior to initiation of the intervention. The primary outcome was the incidence of CDI. Secondary outcomes included incidence of vancomycin resistant enterococcus (VRE) infection and incidence of aGVHD. Results During admission for transplant and at +100 days post-transplant, 5/20 (25%) of patients in the control group developed CDI compared to 0/20 (0%) in the prophylaxis group (p=0.0471). Prophylaxis was not associated with higher rates of VRE infection through day +100 post-transplant (2/20, 10% vs 0/20, 0%, p=0.487). Use of oral vancomycin was not associated with increased incidence of aGVHD, which occurred in 10/20 (50%) of patients in the control group versus (7/20) 35% in the prophylaxis group (p=0.523). Conclusion Prophylaxis with oral vancomycin was associated with a significant reduction in CDI. Use of prophylaxis was not associated with an increased risk for VRE infection and there was no change in incidence of aGVHD. Our review supports the use of prophylaxis, and we will continue to monitor for resistant infections and evaluate the impact on survival. Disclosures Alfred Luk, MD, Karius: Grant/Research Support.

391. Evaluation of oral vancomycin treatment for hospital-acquired Clostridioides difficile infection prophylaxis in a community hospital: A retrospective cohort study

Abstract Background Hospital-acquired (HA) Clostridioides difficile infection (CDI) is among the most common hospital-acquired infections and is a leading cause of morbidity and mortality among hospitalized older adults. Oral vancomycin prophylaxis (OVP) has been demonstrated in recent studies to reduce the incidence of HA CDI. This study aims to evaluate the effectiveness of OVP in the prevention of HA CDI in a community hospital setting. Methods We developed a protocol to administer prophylactic oral vancomycin based on patients’ risk factors and implemented it at our community hospital in Evanston, Illinois, in September 2020. The intervention group consists of patients admitted to our hospital between October 1, 2020, to March 31, 2021, who received OVP. Patients admitted between October 1, 2019, to March 31, 2020, who had at least one risk factor of CDI and met the inclusion criteria of OVP protocol were selected as the control group. Electronic medical records were retrospectively collected and analyzed. Propensity score matching was performed for a one-to-one match between two groups. Logistic regression models were used to study the relationship between HA CDI and independent variables, including OVP, risk factors of CDI, and demographic characteristics. Table 1.Sample characteristics of the control and intervention groups A Student t-test was performed for continuous parameters. A Chi-square test was performed for categorical parameters. Non PPx = control group; OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Results A total of 446 patients (267 in the intervention group and 179 in the control group) were included. The sample characteristics are summarized in Table 1. 4/175 (2.2%) patients in the control group developed HA CDI, compared with 12/255 (4.5%) in the intervention group. Before matching, patients who received OVP (OR=7.62, p=0.010) and had a longer length of stay (LOS, OR=1.11, p=0.002) were found to have increased odds ratios (OR) of development of HA CDI (Table 2). After propensity score matching, 4/176 (2.3%) patients in the control group developed HA CDI, compared with 5/176 (2.8%) (Figure 1). Patients from skilled nursing facilities (SNF, OR=15.41, p=0.021) and with longer LOS (OR 1.15, p=0.005) were found to be associated with higher OR of HA CDI (Table 3). Table 2.The odds ratio of development of hospital-acquired C.diff infection among control and intervention groups. A binary logistic regression model was used for this study. CI = 95% confidence interval. R2 Tujur = coefficients of determination (D); AIC = Akaike’s Information Criteria. OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Figure 1.Propensity score matching of control and intervention groups. (A) Distribution of propensity scores between unmatched and matched control and intervention groups. (B) Distribution balance of propensity score before and after matching. Treatment o = control group; Treatment 1 = OVP intervention group. (C) The distribution balance of covariates used for propensity score calculation before and after matching. (D) Summary of propensity score matching results. HA CDI = hospital-acquired C.diff infection (after propensity score matching). Table 3.The odds ratio of development of hospital-acquired C.diff infection among control and intervention groups after propensity score matching. A binary logistic regression model was used for this study. CI = 95% confidence interval. R2 Tujur = coefficients of determination (D); AIC = Akaike’s Information Criteria. OVP PPx = oral vancomycin prophylaxis group; SNF = skilled nursing facility; LOS = length of stay; PPI = proton pump inhibitor; H2RA = histamine 2 receptor antagonist. Conclusion Prophylactic administration of oral vancomycin to patients with selected risk factors has no statistical significance in reducing or preventing HA CDI. A longer length of hospital stay may be associated with higher risk for developing HA CDI. Disclosures All Authors: No reported disclosures.