Clostridioides Difficile Infection Episode Research Articles

Secondary prophylaxis for Clostridioides difficile infection for patients on non-C. difficile antibiotics: a retrospective cohort study

ObjectivesRecurrent Clostridioides difficile infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus. MethodsWe used data from the largest healthcare provider in Israel to identify all adults aged 18 years or older diagnosed with a first episode of CDI (Index CDI) between February 2018 and December 2022 and subsequently received a non-CDI antibiotic within 2–8 weeks. Patients who received a concurrent prophylactic CDI antibiotic constituted the CDI prophylaxis group. Multivariable Cox proportional hazard regression models were used to examine the association of secondary CDI prophylaxis with CDI recurrence according to the severity of the index CDI (primary objective) and with 4- and 8-week all-cause mortality (secondary objective). ResultsA total of 434 eligible patients were included. Among them, 327 did not receive CDI antibiotic prophylaxis, while 107 did. CDI antibiotic prophylaxis was associated with a significant risk reduction of CDI recurrence with an adjusted HR of 0.51 (95% CI, 0.27–0.97). The magnitude of the association was modified by the severity of the index CDI episode (P for interaction 0.0182). Specifically, the HR for recurrence was 0.163 (95% CI 0.045–0.593) for non-severe CDI, and 1.242 (95% CI 0.524–2.946) for severe CDI. No significant association was found between CDI antibiotic prophylaxis and 4–8 weeks mortality. ConclusionSecondary prophylaxis with CDI antibiotics appears to be associated with a reduced risk of recurrence in patients with previous non-severe CDI episode. Further studies are needed to confirm this finding.

Recurrence of Clostridioides difficile infection and mortality in older inpatients.

The prevalence of Clostridioides difficile infection in older and frail population is extremely high and adverse outcomes, including future recurrences and premature mortality, are common. Nonetheless, the clinical risk profile for Clostridioides difficile recurrence in older people is still controversial. We aimed to investigate: 1) the association between Clostridioides difficile recurrence and 6-month mortality; 2) the risk factors for Clostridioides difficile recurrence after hospital discharge. This is a retrospective study on adults with a first episode of Clostridioides difficile infection admitted to all Internal Medicine and Geriatrics Units of the University Hospital of Ferrara (Italy) between January 2018 and December 2020. For each patient, sociodemographic, clinical and laboratory data were collected through hospital database system. The primary and secondary outcomes were mortality and recurrence within 6months from the first infectious episode, respectively. The mean age of the 386 enrolled patients was 77.8years; 61.7% were females. Twelve percent patients had Clostridioides difficile recurrence and 32.1% patients died during the 6-month follow-up. At Cox analysis, after adjustment for the potential confounders, participants with recurrence reported a twofold risk of death compared to those without recurrence (HR, 95% CI 2.45, 1.59-3.78). Compared to patients treated with metronidazole, those treated with vancomycin showed a lower risk of recurrence (log-rank p < 0.001). Clostridioides difficile recurrence is associated with a higher risk of mortality and it may itself be a marker of frailty and vulnerability. Vancomycin treatment during the infectious episode was associated with lower recurrence rate, as compared to metronidazole.

P1149 Risk of Clostridioides difficile infection in patients with inflammatory bowel disease

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). CDI in IBD patients has been associated with poor clinical outcomes including higher morbidity and mortality. Immunosuppressant therapy has been proposed as a risk factor for CDI. However, the particular relationship between biologic therapy and CDI is controversial. We aimed to assess whether biologic therapy increased the risk of developing CDI in three cohorts of patients with immune-mediated inflammatory diseases (IBD and rheumatic diseases). Methods We conducted a retrospective study including three cohorts: IBD patients receiving biologic therapies (IBD-Bio), IBD patients treated with non-biologic therapies (IBD-Bio-naïve), and patients with rheumatic diseases receiving biologics (RHEUMA-Bio). Different biologic agents were considered for IBD-Bio cohort: infliximab, adalimumab, golimumab, certolizumab, ustekinumab, and vedolizumab. For RHEUMA-Bio, the biologics included were infliximab, adalimumab, golimumab, certolizumab, ustekinumab, secukinumab, etanercept, abatacept, tocilizumab, rituximab, guselkumab and ixekizumab. We estimated the incidence rate (IR) of CDI episodes between 2015 and 2021 among the three cohorts. Risk factors of CDI were assessed using logistic regression model. Furthermore, we performed subgroup analysis to identify risk factors of CDI in the IBD cohorts (IBD-Bio and IBD-Bio-naïve) and within the IBD-Bio cohort. We used R software for data analysis. Results Overall, we included 1868 patients, 603 in IBD-Bio, 440 in IBD-Bio-naïve, and 825 in the RHEUMA-Bio cohort. The number of CDI episodes was 3, 42, and 25 for the RHEUMA-Bio, IBD-Bio, and IBD-Bio-naïve cohorts, respectively. The IR for CDI was 1.27 100 person-years (95% confidence interval [95% CI], 0.91-1.71) for IBD-Bio, followed by 0.95 100 person-years (95% CI 0.61-1.40) for IBD-Bio-naïve and declined to 0.07 100 person-years (95% CI 0.01-0.20) for RHEUMA-Bio cohort. We identified having IBD (odds ratio [OR]:18.98, CI 95% 5.82- 61.92, p&amp;lt;0.001) as the major risk factor for developing CDI after adjusting for age, sex, need for biologics, and comorbidities in the three cohorts. Among IBD patients, there were no differences in CDI between biologic and naive cohorts. Within the IBD-Bio cohort, the number of biologics received (OR: 1.56, CI 95% 1.22- 2.01, P&amp;lt;0.001) and short disease duration (1.08, CI 95% 1.04- 1.13, P&amp;lt;0.001) were associated with a higher risk of CDI. Conclusion The major risk factor associated with CDI development was the diagnosis of IBD. Biologic therapy was not associated with a higher risk of CDI. In IBD patients on biologic therapy, the number of biologics received increased the risk of CDI.

Microbiome profile and calprotectin levels as markers of risk of recurrent Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is the main cause of nosocomial diarrhoea in developed countries. Recurrent CDI (R-CDI), which affects 20%-30% of patients and significantly increases hospital stay and associated costs, is a key challenge. The main objective of this study was to explore the role of the microbiome and calprotectin levels as predictive biomarkers of R-CDI. We prospectively (2019-2021) included patients with a primary episode of CDI. Clinical data and faecal samples were collected. The microbiome was analysed by sequencing the hypervariable V4 region of the 16S rRNA gene on an Illumina Miseq platform. We enrolled 200 patients with primary CDI, of whom 54 developed R-CDI and 146 did not. We analysed 200 primary samples and found that Fusobacterium increased in abundance, while Collinsella, Senegalimassilia, Prevotella and Ruminococcus decreased in patients with recurrent versus non-recurrent disease. Elevated calprotectin levels correlated significantly with R-CDI (p=0.01). We built a risk index for R-CDI, including as prognostic factors age, sex, immunosuppression, toxin B amplification cycle, creatinine levels and faecal calprotectin levels (overall accuracy of 79%). Calprotectin levels and abundance of microbial genera such as Fusobacterium and Prevotella in primary episodes could be useful as early markers of R-CDI. We propose a readily available model for prediction of R-CDI that can be applied at the initial CDI episode. The use of this tool could help to better tailor treatments according to the risk of R-CDI.

First Clostridioides difficile Recurrence Is Highest Following Concomitant Antimicrobial Administration During and Within 30 Days of Treatment.

Clostridioides difficile infection (CDI) is an epidemic with the strongest risk factor being antibiotic usage. Patients who get CDI frequently require concomitant antibiotics for other indications around the time of their infection. To assess the recurrence of CDI (rCDI) in patients receiving concomitant antibiotics at the same time or shortly thereafter treatment of CDI. We retrospectively reviewed records for patients with their first inpatient CDI episode. Patients were grouped into those who didn't receive concomitant antibiotics (noABx), those receiving antibiotics at the same time as treatment of CDI (ABxDURING), those receiving antibiotics within 30-days of completion of CDI therapy (ABxAFTER) and those who received antibiotics both during and after CDI treatment (ABxDuringAfter). Our primary outcome was recurrence within 14-90days; other outcomes included ICU stay at the time of diagnosis, 30-day ICU transfer, 30-day colectomy, and readmission. 457 patients had CDI during admission (mean age: 66.4years, 51.9% female). 64.1% were exposed to concomitant antibiotics. Recurrence rates were 4.3%, 6.1%, 13.8% and 19.1%, for noABx, ABxDURING, ABxAFTER and ABxDuringAfter, respectively. Patients with ABxDuringAfter had the highest rates of rCDI when compared to noABx [OR 5.67, 95% CI (2.18-14.72)]. There is a high rate of utilization of non-CDI antibiotics during or shortly after completing CDI treatment with high rates of recurrence within 90-days. Concomitant antimicrobials alter the opportunity for the microbiota to re-grow and worsens dysbiosis leading to increases in recurrence. Concomitant antimicrobial stewardship remains important in patients being treated for CDI and shortly after treatment.

Clostridioides difficile Infection in Inflammatory Bowel Disease Patients: A Systematic Review of Risk Factors and Approach in Management.

Clostridioides difficile infection (CDI) is one of the most common diseases associated with medical care, having a more significant impact on patients with inflammatory bowel disease (IBD). The latest studies have proposed a change in management for CDI in IBD patients. This study aims to perform a systematic review that explores the risk factors associated with the infection and the most optimal approach in management. Multiple databases were used for this research, including PubMed, Google Scholar, Science Direct, and Cochrane Library. Studies published in the last five years in the English language were selected based on pre-established criteria. The quality assessment used was the Assessment of Multiple Systematic Review, the Newcastle-Ottawa Scale, and the Scale for the Assessment of Narrative Review Articles. Twelve studies met the inclusion criteria in this systematic review, including literature reviews, a case and control study, and systematic reviews and meta-analyses. Based on the findings in this research, we conclude that the treatment for an initial episode of CDI in IBD patients is the use of antibiotics, vancomycin, or fidaxomicin. For episodes of recurrent CDI (rCDI), fetal microbiota transplantation should be considered. The most common risk factors associated are gut microbiota disturbances, the use of antibiotics, and hospitalization. Due to a wide range of risk factors mentioned in some studies but disregarded in others, further research is needed to determine the most prevalent risk factors.

Increased Incidence and Risk of Septicemia and Urinary Tract Infection After Clostridioides difficile Infection.

Although increased occurrence of septicemia in persons with Clostridioides difficile infection (CDI) has been reported, incidence rates and risk of septicemia and urinary tract infection (UTI) after CDI are unclear. The first episode of CDI was identified using 2011-2017 MarketScan and CMS Medicare data and CDI cases categorized by standard surveillance definitions. Uninfected persons were frequency matched 4:1 to cases by the CDI case surveillance definition. Multivariable Cox proportional hazards models were used to identify risk factors for septicemia and UTI within 90 days of CDI onset, accounting for the competing risk of death in the Medicare population. The incidence of septicemia was highest after hospital-onset CDI in the Medicare, younger commercial, and younger Medicaid populations (25.5%, 15.7%, and 19.5%, respectively) and lowest in those with community-associated CDI (3.8%, 4.3%, and 8.3%, respectively). In contrast, the incidence of UTI was highest in those with other healthcare facility onset CDI in all 3 populations (32.1%, 24.2%, and 18.1%, respectively). Hospital-onset CDI was associated with highest risk of septicemia compared with uninfected controls in all 3 populations. In the younger populations, risk of septicemia was more uniform across the CDI surveillance definitions. The risk of UTI was significantly higher in all CDI surveillance categories compared to uninfected controls, and among CDI cases it was lowest in those with community-associated CDI. The incidence of septicemia is high after CDI, particularly after hospital-onset infection. Additional preventive measures are needed to reduce infectious complications of CDI.

The management of Clostridioides difficile infection: from empirism to evidence.

Clostridioides difficile infection (CDI) in clinical practice represents a challenge for its management and also prevention of recurrence. Even though there are updated guidelines for infection prevention, control and treatment, CDI remains a leading cause of healthcare acquired diarrhea with increasing incidence in the community. We present here a synthesis of the most recent international guidelines on the management of CDI. In 2021 updated guidelines on the treatment of CDI in adults were published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These guidelines focused on CDI management in adults, including new data on the clinical efficacy of Fidaxomicin (FDX) and Bezlotoxumab. The 2017 publication of IDSA and SHEA - Clinical Practice Guidelines for Clostridium difficile infection also included pediatric treatment recommendations that are not a part of the 2021 update. Vancomycin (VAN) treatment for an initial CDI episode remains an acceptable alternative to FDX, considering the monetary and logistical challenge of acquiring FDX. There is growing literature on fecal microbiota transplantation (FMT) and the 2021 guidelines describe its role in severe complicated refractory CDI cases and for which surgical management is not feasible. Moreover, there are new data on the secondary prophylaxis with VAN in refractory CDI in patients with risk factors who receive broad spectrum antibiotics.

Use of Fecal Microbiota, Live-jslm (RBL) in the Routine Clinical Management of Clostridioides Difficile—First Five Cases

Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections. The current recommended treatment regimen for an initial episode of CDI is fidaxomicin (200 mg twice daily for 10 days) or vancomycin (125 mg, four times daily for 10 days) as an acceptable alternative. Unfortunately, in approximately 25–35% of cases, CDI recurs within 1–2 months of the initial infection. After a first recurrence, patients are substantially more likely to have a subsequent recurrence, with approximately 50–60% of these patients experiencing multiple recurrent CDI (rCDI). We report our early clinical experience in a multi-center community infectious disease private practice setting with the initial five patients who received the live biotherapeutic product, REBYOTA (RBL). Methods: Five patients who had experienced multiple recurrent episodes of C difficile infection and had failed the standard antibiotic therapy were prescribed the live biotherapeutic product REBYOTA (RBL). The product was administered as a single dose via the rectum. The patients were followed for eight weeks for clinical response and adverse events. Results: Patients included three males and two females, aged 20–86 years with recurrences ranging from 3 to 6 in the previous 18 months. Four patients received standard vancomycin, two patients had vancomycin taper, two had fidaxomicin and one had bezlotoxumab (Zinplava). RBL was administered easily and in less than 10 minutes. No new symptoms occurred within seven days. No recurrence was reported at eight weeks. No adverse events were reported, including no bacteremia or fungemia. No patient incurred expenses other than deductible costs. Conclusion: In a real-world setting, our initial five patients found that RBL was easy and convenient to administer with normalization of formed stools and an excellent overall clinical response at eight weeks. Furthermore, no adverse events were reported.

Utilizing vancomycin as secondary prophylaxis for the prevention of recurrent Clostridioides difficile infection

Background: Recurrent Clostridioides difficile infection (CDI) is associated with significant morbidity, mortality, and healthcare-related costs. Although data are minimal, agents including oral vancomycin have been used as secondary prophylaxis to prevent recurrent CDI. Methods: We conducted a randomized, double-blind, placebo-controlled trial to determine the effectiveness of vancomycin at preventing CDI from October 2019 to September 2022. Eligible patients had a history of at least 1 episode of CDI and were receiving systemic antibiotics for another condition. Participants were randomized 1:1 to oral vancomycin 125 mg by mouth twice daily and were interviewed at 1, 2, and 3 months thereafter to assess recurrence. We enrolled 26 patients: 15 completed the 1-month interview, 12 completed the 2-month interview, and 11 completed the full study. Those 15 participants who did not complete the 3-month interview were considered dropouts. The final sample for this study included those 11 participants who completed all interviews. Demographics and outcomes are shown in Table 1. Results: One case of recurrent CDI was reported at the 1-month interview and a second was reported at 3 months; both cases had received the placebo. The study was terminated early due to low enrollment. Conclusions: Although our results did not reach statistical significance and this study was limited in small sample size, our findings suggest that secondary prophylaxis with oral vancomycin may be beneficial in patients who are actively receiving antibiotics, which is consistent with prior retrospective studies. Future studies with larger sample sizes are still needed to examine this important question of whether secondary prophylaxis is useful for preventing recurrent CDI.Disclosure: None

Budget Impact Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) for Preventing Recurrent Clostridioides difficile Infection in the US.

Patients with Clostridioides difficile infection (CDI) often experience recurrences (rCDI), which are associated with high morbidity, mortality, and healthcare expenditures. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We quantified the budget impact of FMBL during the first 3years following introduction from a third-party US payer perspective. A decision-tree model was used to estimate the budget impact of one-course FMBL by comparing costs under the scenario with FMBL to the scenario without FMBL (standard of care) in patients with one or more (≥ 1) recurrences after a primary episode of CDI and had completed ≥ 1 round of antibiotic treatments. Drug costs, rCDI-related medical costs, and budget impact over 1-3years were estimated in 2022 US dollars. One-way sensitivity analyses were performed. For an insurance plan with a population size of 1,000,000, 468 patients per year were estimated to have ≥ 1 rCDI. The budget impact of one-course FMBL at $9000/course was cost-saving at an» average of -$0.0039 on a per-member-per-month (PMPM) basis, an average of -$8.30 on a per-treated-member-per-month (PTMPM) basis, and a total of -$139,865 on a plan level assuming 5%, 15%, and 20% of patients receive FMBL over 1-3years, respectively. The scenario with FMBL entry was associated with higher drug costs (difference at $0.0474 PMPM; $101.26 PTMPM; $1,706,445 total plan) and lower rCDI-related medical costs (difference at -$0.0513 PMPM; -$109.56 PTMPM; -$1,846,309 total plan). The budget impact of FMBL in patients at first rCDI was cost-saving at -$0.0139 PMPM, -$84.78 PTMPM, corresponding to an annual savings of $500,022. FMBL has a cost-saving budget impact for a US payer, with higher initial drug costs being offset by savings in rCDI-related medical costs. Greater cost saving was found in patients at first recurrence.

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.

Live Fecal Microbiota (Rebyota) for Prevention of CDI Recurrence

The FDA has approved Rebyota (Ferring), a rectally-administered, live fecal microbiota suspension, for prevention of additional recurrences of Clostridioides difficile infection (CDI) following antibiotic treatment for a recurrent episode of CDI in adults. Rebyota is the first microbiome-based treatment to be approved for this indication. It is not approved for initial treatment of CDI. Fecal microbiota transplantation (FMT) has been used in patients with multiple CDI recurrences.

Role of previous systemic antibiotic therapy on the probability of recurrence after an initial episode of Clostridioides difficile infection treated with vancomycin.

To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin. Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8 weeks were included. Previous antibiotic exposure up to 90 days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed. Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); P = 0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); P = 0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving ≥5 days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06-0.29; P < 0.0001] whereas exposure for ≥5 days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4-27.1; P < 0.0001). Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.

Real-world Use of Bezlotoxumab and Fecal Microbiota Transplantation for the Treatment of Clostridioides difficile Infection.

We aimed to describe the frequency of use and effectiveness of bezlotoxumab (BZX) and fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) in real-world practice. This was a retrospective study conducted in a university hospital in which adult patients treated with BZX or FMT from January 2018 to April 2021 were included. The primary objective was to evaluate the effectiveness of BZX and FMT in preventing early (within 8 weeks) and late (within 1 year) CDI recurrences (rCDI). A multivariate analysis of risk factors for early recurrence was performed. Of 1377 consecutive CDI episodes, 117 (8.5%) received BZX or FMT, with full information available for 100 of the episodes: 51 received BZX, and 49 received FMT. BZX was used mostly in immunosuppressed patients (66.7%) and in first episodes or first recurrences in 70.6% of the cases. FMT was prescribed only in CDI recurrences. Despite the different conditions of the patients, there were no significant differences between BZX and FMT in preventing early rCDI (19.6% vs 24.5%; P = .55) or late rCDI (9.8% vs 18.4%; P = .31). In the multivariate analysis, risk factors for recurrence were presence of ≥2 previous rCDI episodes (odds ratio [OR], 2.90; 95% CI, 1.03-8.63) and use of non-CDI antibiotics (OR, 3.45; 95% CI, 1.24-9.57). BZX and FMT were infrequently used in real-world practice. Both treatments had similar effectiveness in preventing CDI recurrence despite their application to different populations.

Short- and long-term follow-up after fecal microbiota transplantation as treatment for recurrent Clostridioides difficile infection in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Treatment of CDI in patients with IBD is challenging due to higher failure rates and concomitant IBD activity. We performed a multicentre cohort study in patients with IBD who received fecal microbiota transplantation (FMT) for recurrent CDI (rCDI), to further investigate factors that influence the clinical outcome and course of both rCDI and IBD. This is a multicentre cohort study conducted in five European FMT centres. Adult IBD patients treated with FMT for rCDI were studied. Cure was defined as clinical resolution of diarrhoea or diarrhoea with a negative C. difficile test. The definition of an IBD flare was record based. Long-term follow-up data were collected including new episodes of CDI, IBD flares, infections, hospital admissions, and death. In total, 113 IBD patients underwent FMT because of rCDI. Mean age of the patients was 48 years; 64% had ulcerative colitis. Concomitant rCDI was associated with an IBD flare in 54%, of whom 63% had received IBD remission-induction therapy prior to FMT. All FMT procedures were preceded by vancomycin treatment, 40% of patients received FMT via colonoscopy. CDI cure rate was 71%. Long-term follow-up data were available in 90 patients with a median follow-up of 784 days (402-1251). IBD activity decreased in 39% of patients who had active IBD at baseline, whereas an IBD flare occurred in only 5%. During follow-up of up to 2 years, 27% of the patients had infections, 39% were hospitalized, 5% underwent colectomy, and 10% died (median age of these latter patients: 72 years). FMT for rCDI in IBD patients is safe and effective, and IBD exacerbation after FMT is infrequent. Further studies should investigate the effects on IBD course following FMT.

389. Epidemiology of Multiple Recurrent Clostridioides difficile in the Atlanta Metropolitan Area between 2016 and 2019

Abstract Background Patients with multiple recurrences of Clostridioides difficile infection (CDI) have longer hospital stays and lower quality of life. Recent changes in therapies and strains of CDI make understanding recurrent CDI in the general population critical as these patients may benefit from microbiota restoring therapies rather than antibiotics alone. Methods Georgia’s Emerging Infections Program (supported by CDC) conducts CDI surveillance in 8 counties around metropolitan Atlanta, GA (population ∼4 million). CDI is defined as any C. difficile-positive specimen with no positive test in the prior 2 weeks. We evaluated CDI between Jan 2015 through Dec 2019 and captured recurrent CDI (CDI test date 2-52 weeks following previous CDI) for 2016-2019 which were categorized as single episode only, recurrent (2 episodes ≤ 1 year) or multiple recurrent (&amp;gt;2 episodes ≤ 1 year). Year was attributed to date of final episode. Census data was used to determine crude and age-specific incidence. Bivariate and multivariable logistic regression was used to estimate odds for multiple recurrent compared to single recurrent CDI with demographic, comorbidity and treatment related covariates. Results Over 4 years 13,745 patients had at least one episode of CDI, 2,930 (20%) had ≥ 1 recurrence and 916 (30%) of these progressed to multiple recurrence. Between 2016 to 2019, incidence of single CDI decreased 25% from 93/100,000 to 69/100,000 (P&amp;lt; 0.01). Multiple recurrent CDI decreased 45% from 9/100,000 to 5/100,000) (P&amp;lt; 0.01); incidence in the 80+ age group was highest and where decreased incidence was most dramatic during the study period (Figures). Time between 1st and 2nd episode was longer among patients with single recurrent than multiple recurrent CDI (median 12 weeks vs. 9 weeks, P&amp;lt; 0.01).. Independent predictors of multiple recurrence were fewer days (&amp;lt; 90) between episodes (aOR: 1.87 P&amp;lt; 0.01) and chronic renal disease (aOR: 1.59 , P&amp;lt; 0.01). Figure 1:Annual Incidence of CDI by age group. A) Incidence of CDI among patients with only a single episode of CDI within 365 days. B) Incidence of CDI among patients with three or more episodes (two or more recurrence) within 365 days. RR documented compares 2016 to 2018 incidence in the 80+ age group Conclusion Time between 1st and 2nd CDI most strongly predicts likelihood of progression to multiple recurrences. Of all measured comorbid conditions, renal disease was most predictive. These findings may help to identify patients at high risk for progression for advanced interventions such as microbiota modifying therapies. Disclosures Scott Fridkin, MD, Pfizer: Grant/Research Support Colleen Kraft, MD MS, Rebiotix Inc: Advisor/Consultant|SERES: Advisor/Consultant.

393. Healthcare and Out-of-Pocket Costs Associated With Clostridioides difficile Infection Among US Adults 18–64 Years of Age

Abstract Background Limited data are available on healthcare costs associated with Clostridioides difficile infection (CDI) among adults &amp;lt; 65 years of age. Methods This retrospective cohort study used Optum’s de-identified Clinformatics® Data Mart to identify first CDI episodes from 2016–2019 among individuals 18–64 years of age insured under commercial plans. CDI was defined by ICD9/ICD10 diagnosis codes or a combination of CDI diagnosis/testing with antibiotic treatment. Healthcare costs were evaluated among CDI+ cases and 1:1 propensity score-matched CDI− controls. Both CDI+ cases and controls had continuous database enrollment for ≥12 months prior; follow-up continued through the earliest of death, disenrollment or 12 months post-index. Costs were analyzed by age group, acquisition type, and hospitalization status within 2 months of the CDI index date. Results We identified 13,820 CDI+ cases and 4,027,386 potential controls; 12,999 cases (18–49 y, n=6667; 50–64 y, n=6332) were matched to a control. In the 50–64-year matched groups, mean total healthcare costs at 2 months post-index were $18,453 (CDI+) and $6819 (CDI−); $11,634 in excess costs were attributable to CDI (Figure 1A). Mean attributable costs were higher for hospitalized healthcare-associated ($68,745) and hospitalized community-associated ($37,646) cases than non-hospitalized healthcare- or community-associated cases ($8333 and $2953, respectively). The mean attributable out-of-pocket (OOP) cost in the 50–64-year age group was $573 and was higher for community-associated vs healthcare-associated cases (Figure 1B). Overall CDI-attributable costs in the 18–49-year age group trended similarly but were mostly lower for total healthcare costs ($7826 [CDI+, $12,019; CDI−, $4193]; Figure 2A) and slightly higher for OOP healthcare costs ($642 [CDI+, $954; CDI–, $311]; Figure 2B). Conclusion CDI-attributable healthcare costs among US individuals 18–64 years of age are substantial, particularly for those hospitalized for CDI. Effective prevention in younger adults may significantly reduce healthcare resource utilization and costs to both the healthcare system and patients. Funded by Pfizer Inc. Disclosures Holly Yu, MSPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Tamuno Alfred, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jingying Zhou, MA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jennifer Judy, MS, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Margaret A A. Olsen, PhD, MPH, Pfizer Inc: Advisor/Consultant|Pfizer Inc: Grant/Research Support.

392. Guideline adaptation of fidaxomicin as first-line therapy for Clostridioides difficile infection in institutions across the United States

Abstract Background In 2021, Clostridioides difficile infection (CDI) treatment guidelines were updated to recommend fidaxomicin over oral vancomycin as first-line therapy in initial and recurrent CDI episodes. Prior to this update, fidaxomicin use in management of CDI was limited, as cheaper alternatives were recommended as first-line therapy. The purpose of this study was to assess the guideline adaptation of fidaxomicin as first-line therapy in CDI management in institutions across the United States (US) and to identify barriers to its use. Methods An electronic survey was distributed to members of the American Society of Health-System Pharmacists in April 2022. Baseline demographics, current practices, and barriers to fidaxomicin use were collected. Results were analyzed using descriptive statistics. Fisher’s Exact Test was used to compare categorical variables. Results Based on 63 responses, majority of institutions (41/63, 65%) did not recommend use of fidaxomicin as first-line therapy for CDI. While most hospitals reported having institution specific CDI guidelines (48/63, 76%), over half of institutions with CDI guidelines still recommended oral vancomycin as first-line therapy (26/48, 54%). None of the institutions without CDI guidelines (0/15, 0%) recommended use of fidaxomicin as first-line therapy and majority of them (12/15, 80%) did not have fidaxomicin on formulary or restricted its use to ID services. Recommendation of fidaxomicin as first-line therapy was significantly higher in institutions with CDI guidelines versus those without (46% vs 0%, Fisher’s Exact 0.0006, p&amp;lt; 0.05). Approximately 92% (58/63) of respondents reported at least 1 barrier to using fidaxomicin, with 39.6% (25/63) reporting 2 or more barriers to use. Barriers identified were cost (55/63, 87.3%), lack of formulary inclusion (14/63, 22.2%), lack of provider familiarity (13/63, 20.6%) and inability of patients to afford upon discharge (7/63, 11.1%). Conclusion Majority of institutions do not currently recommend use of fidaxomicin as first-line therapy for CDI despite the recent guideline updates. Institutions with CDI treatment guidelines were more likely to recommend use fidaxomicin as first-line therapy. Cost and lack of formulary inclusion were cited as the most frequent barriers to fidaxomicin use. Disclosures All Authors: No reported disclosures.

Risk Factors Associated with Severe Clostridioides difficile Infection in Patients with Cancer.

Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer. This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C.difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels. On univariate analysis, factors associated with severe CDI included the presence of toxinA/B in stools (odds ratio [OR] 2.14 [1.05-4.36] p = 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09-6.50] p = 0.03). Although alpha and beta diversity was similar between disease severity groups and toxinA/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseri were associated with protection from severe CDI (p < 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure. Use of metronidazole for non-CDI indications within 90days prior to diagnosis and presence of toxinA/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.