Severe Clostridium Difficile Infection Research Articles

Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.

Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI. We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression. Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks. Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.

Fidaxomicin versus oral vancomycin for Clostridioides difficile infection among patients at high risk for recurrence based on real-world experience.

Clostridioides difficile infection (CDI) is a common nosocomial infection and is associated with a high healthcare burden due to high rates of recurrence. In 2021 the IDSA/SHEA guideline update recommended fidaxomicin (FDX) as first-line therapy. Our medical center updated our institutional guidelines to follow these recommendations, prioritizing FDX use among patients at high risk for recurrent CDI (rCDI). This pre- post- quasi-experimental study included patients with a presumptive diagnosis of CDI at risk for recurrence (age >/= 65 years, immunocompromised, severe CDI) that received vancomycin (VAN) or FDX between October 2019 to October 2022. Patients who received bezlotoxumab, had fulminant CDI, or received <10 days of the same antibiotic for their full treatment course were excluded. Patients were evaluated for rCDI within 8 weeks of completion of therapy, subsequent episodes of CDI within 12 months, and CDI-related admissions within 30 days. Of 397 CDI regimens evaluated, 196 received VAN and 201 received FDX. Rates of rCDI (9.2% vs 10%, P = 0.86), subsequent CDI within 12 months of therapy completion of therapy (19.4% vs 26%, P = 0.12) and 30-day CDI-related readmissions (3% vs 4.5%, P = 0.6) were similar between patients who received VAN versus FDX. Outcomes were similar between patients treated with FDX and VAN for the treatment of CDI among those at high risk for rCDI, using our outlined criteria. Although we observed a trend toward lower rates of rCDI among immunocompromised patients, this finding was not significant. Further investigation is needed to determine which patients with CDI may benefit from FDX.

Recurrent Clostridioides difficile infections in solid organ transplant recipients: The international CALIPSO study

To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n=114,59.7%), vancomycin+metronidazole (n=39,20.4%), metronidazole (n=26,13.6%), fidaxomicin (n=9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p<.001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p=.001) were factors independently associated with recurrence. Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.

EP492 - Fulminant Clostridium difficile infection post reversal of ileostomy

Abstract Aims Clostridium difficile infection (CDI) is an important cause of diarrhoea in hospitalized patients, varying from mild to fulminant forms. Fulminant CDI subsequent to the reversal of ileostomy, despite negative C. difficile toxin, is rare. Results We present the case of a 75-year-old male with a history of atrial fibrillation, chronic obstructive pulmonary disease and hypertension, who underwent elective ileostomy reversal following an emergency laparotomy and end ileostomy for acute diverticular bleed two years prior. Initially uncomplicated, the patient developed mild CDI on postoperative day 4 with white cell count of 18.6×109/L, evolving rapidly to severe CDI by day 6, characterized by worsening abdominal pain, worsening leukocytosis (30×109/L), and acute kidney injury stage 1. Patient was started on Vancomycin and Metronidazole, Computed Tomography (CT) scan showed uncomplicated sigmoid colitis. Despite aggressive antibiotic therapy and fluid resuscitation, the patient deteriorated on day 8, presenting with fulminant CDI, hypotension, elevated lactate of 2.6 and leukocytes of 46×109/L. Subsequent CT Imaging revealed pneumatosis coli. At that point, the patient's NELA score was 53.4%. The patient was stabilised by the critical care team prior to emergency subtotal colectomy and end ileostomy due to suspected colonic perforation. Surgical finding showed transverse colon inflammation with a hepatic flexure abscess. Patient required 14-day intensive care unit stay and 13 days of ward management before he is fit for rehab. Conclusion This case highlights the potential for fulminant CDI post-ileostomy reversal and highlights the challenges in managing such complications, necessitating prompt recognition and interventions to mitigate adverse outcomes.

Efficacy of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection: A systematic meta-analysis.

To compare the efficacy, recurrence rate, adverse event rate and mortality of fidaxomicin compared with vancomycin in treating different types of Clostridium difficile infection (CDI). A systematic search was conducted on PubMed, Embase, Web of Science, Cochrane Library and clinical trial registration databases for research on fidaxomicin versus vancomycin in the treatment of CDI and the retrieval period extended from the establishment of the database to July 22, 2022. A total of 15 studies were included, including 8 RCTs and 7 retrospective cohort studies. Results showed that there was no significant difference in the overall efficacy of the treatment between fidaxomicin and vancomycin, and results in the subgroups of CDI hypervirulent strains and recurrent CDI were obtained, but vancomycin was more effective than fidaxomicin in the treatment of severe CDI (RR = 0.94, 95% CI: 0.90-0.98, P < .01). Results showed that fidaxomicin is superior to vancomycin in terms of 40-day recurrence rate (RR = 0.52, 95% CI: 0.38-0.70, P < .01), 60-day recurrence rate (RR = 0.38, 95% CI: 0.21-0.69, P < .01) and 90-day recurrence rate (RR = 0.62, 95% CI: 0.50-0.77, P < .01). For the recurrence rate of the treatment in CDI hypervirulent strains, severe CDI and recurrent CDI, there was no significant difference between the 2 groups. In addition, there was no significant difference in the incidence of clinical adverse reactions, and same outcomes appeared in all-cause mortality at 40-day, severe CDI and recurrent CDI, but fidaxomicin was superior to vancomycin in all-cause mortality over 60-day (RR = 0.57, 95% CI: 0.34-0.96, P = .03). There were no significant differences between fidaxomicin and vancomycin in the treatment of CDI in therapeutic effectiveness and adverse reactions, while fidaxomicin was superior to vancomycin in terms of recurrence rate and long-term mortality, and vancomycin is more effective in treating severe CDI.

Clostridioides difficile and Gut Microbiota: From Colonization to Infection and Treatment.

Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile's role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota.

Occurrence and trends of Clostridioides difficile infections in hospitalized patients: a prospective multi-centre cohort study in six German university hospitals, 2016–2020

For Clostridioides difficile infections (CDIs) in Germany no longitudinal multi-centre studies with standardized protocols for diagnosing CDI are available. Recent evaluations of general surveillance databases in Germany indicate a downward trend in CDI rates. We aimed to describe the actual burden and trends of CDI in German university hospitals from 2016 to 2020. Our study was a prospective multi-centre study covering six German university hospitals. We report the data in total, stratified by year, by medical specialty as well as by CDI severity. Multi-variable regression analyses were performed to assess risk factors for severe CDI. We registered 3780 CDI cases among 1,436,352 patients. The median length of stay (LOS) of CDI cases was 20 days (interquartile range 11-37) compared with a general LOS of 4.2 days. In-hospital all-cause mortality in CDI patients was 11.7% (N= 444/3780), while mortality attributed to CDI was 0.4% (N= 16/3761). CDI recurrence rate was comparatively low at 7.2%. The incidence density of severe healthcare-associated healthcare onset (HAHO)-CDI showed a significant decrease from 2.25/10,000 patient days (pd) in 2016 to 1.49/10,000 pd in 2020 (trend calculation P=0.032). Compared with a European point-prevalence study in 2013/2014, where overall CDI incidence density was 11.2 cases/10,000 pd in Germany (EUCLID), we see in our study halved overall CDI rates of 5.6 cases/10,000 pd in 2020. Our study shows current data on the distribution of CDI cases in German university hospitals and thus provides international comparative data on the key indicators of CDI.

Clinical Characteristics and Cycle Thresholds Among Discordant and True Positive Test Results for Clostridiodes difficile

Background: The diagnosis of Clostridioides difficile infection (CDI) is challenging. Despite guideline-directed, multistep testing algorithms and diagnostic stewardship, the treatment of C. difficile colonization persists. The testing algorithm at our system utilizes an initial real-time PCR test (PCR) for Toxin B gene, which if positive, reflexes to an enzyme immunoassay (EIA) for detecting Toxins A and B. Discordant results (PCR +/EIA -) are suggestive of colonization, but the majority of patients with discordant results are treated for CDI. Correlation of C. difficile EIA B polymerase chain reaction (PCR) cycle thresholds (Ct) with the presence of free EIA and disease severity has been observed, but the ability to use Ct in the decision to treat patients with discordant results is unclear. Our study assesses if Ct values and other clinical characteristics favor treatment in select patients with discordant Methods: A retrospective chart review was performed of adult patients (≥ 18-year-old) with positive C. difficile PCR results that were admitted to our health system between June 01 and August 31, 2023. C. difficile PCR and Ct results were obtained by Cepheid GeneXpert and Toxin A and B EIA results were obtained by Meridian Bioscience Immunocard. Patients with discordant (PCR+/EIA) and true positive (PCR+/EIA+) results were compared. We assessed demographics, past medical history, clinical characteristics, severity of illness, PCR Ct values, treatment, and clinical outcomes including: 30-day all-cause mortality and re-admission, and 60-day CDI repeat testing and treatment. Results Of the 122 patients identified, 89 patients had discordant results and 43 had true positive Results: Severity of illness and other clinical and laboratory characteristics were similar between both groups. Mean Ct values were significantly lower for true positive results compared to discordant results, 24.28 vs 29.27, respectively (p26 (p=.08). Of the patients with discordant results, 73 completed treatment for CDI and no difference in clinical outcomes was observed compared to patients with discordant results that were not treated. Conclusion Ct values were lower among patients with true positive results compared to patients with discordant Conclusion: There were no statistically significant different rates of severe or fulminant CDI among patients with discordant results and Ct values &lt; 26, although this finding may be limited by sample size and Ct may be helpful in deciding which discordant patients to treat.

Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection

Background and aimsClostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting. MethodsThis multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) eight weeks after the last FMT treatment. Secondary outcomes included CDAD cure one and eight weeks after the first FMT treatment and 90-day mortality following positive C. difficile test. ResultsWe included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range (IQR) 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%, 95% confidence interval (CI) 71-79%) at week one. At week eight, 255 patients (55%, 95% CI 50-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%, 95% CI 75-82%). The 90-day mortality was 10% (95% CI 8-14%). ConclusionRepeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival.

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.

IL-13 protects from C. difficile colitis

ObjectivesClostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. We have previously discovered that antibiotic disruption of the gut microbiota decreases intestinal IL-33 and IL-25 and increases susceptibility to CDI. We further found that IL-33 promotes protection through type 2 Innate Lymphoid Cells (ILC2s), which produce IL-13. However, the contribution of IL-13 to disease has never been explored. MethodsWe used a validated model of CDI in mice, in which we neutralized via blocking antibodies, or administered recombinant protein, IL-13 to assess the role of this cytokine during infection using weight and clinical scores. Fluorescent activated cell sorting (FACS) was used to characterize myeloid cell population changes in response to IL-13 manipulation. ResultsWe found that administration of IL-13 protected, and anti-IL-13 exacerbated CDI. Additionally, we observed alterations to the monocyte/macrophage cells following neutralization of IL-13 as early as day three post infection. We also observed elevated accumulation of myeloid cells by day four post-infection following IL-13 neutralization. Neutralization of the decoy receptor, IL-13Rα2, resulted in protection from disease, likely through increased available endogenous IL-13. ConclusionsOur data highlight the protective role of IL-13 in protecting from more severe CDI and the association of poor responses with a dysregulated monocyte-macrophage compartment. These results increase our understanding of type 2 immunity in CDI and may have implications for treating disease in patients.

Epidemiologic and Clinical Characteristics and Risk Factors for Severe Community-Acquired Clostridium Difficile Infection in Children.

Although children most frequently suffer from milder forms of community-acquired Clostridium difficile infection, severe cases and fatal outcomes have been recorded. In this study we identified older children (>12 years of age) and patients who had surgery up to 6 months before Clostridium difficile infection onset as a subgroup at somewhat higher risk for severe community-acquired Clostridium difficile infection.

Is shorter also better in the treatment of Clostridioides difficile infection?

To assess the effectiveness of shortened regimens of vancomycin or fidaxomicin in the treatment of Clostridioides difficile infection (CDI). Adult patients with CDI hospitalized from January 2022 to May 2023 were included in this observational study. In patients with CDI treated with vancomycin or fidaxomicin, antibiotic treatment was discontinued after either 5 or 7 days of vancomycin or 5 days of fidaxomicin if there was a clinical response and improvement in laboratory parameters. The control cohort was treated with the standard 10 day regimen of either vancomycin or fidaxomicin. The follow-up was 60 days. Causative C. difficile strains were characterized by ribotyping and toxin gene detection when available. Twenty-five patients (median age 76 years) received shortened treatment with vancomycin (n = 21), or fidaxomicin (n = 4). Five cases fulfilled the criteria for severe CDI. Twenty-three patients completed follow-up; two died from causes other than CDI, and two developed recurrent CDI (8.0%). Ribotypes (RTs) 001 and 014 were the most prevalent with 20% each. In two C. difficile isolates, binary toxin genes were detected (RTs 078 and 023). In the control group of 22 patients recurrent CDI developed in 5 patients (22.7%). No statistically significant differences were found between the groups. Shortened treatment regimens for CDI with vancomycin and fidaxomicin were shown to be effective in our cohort of patients compared with 10 days of treatment. The recurrence rate was lower in the study group. A larger, prospective, double-blind, randomized, multicentre study is needed to support our findings.

Case Series: Efficacy of Polyclonal Intravenous Immunoglobulin for Refractory Clostridioides difficile Infection.

Intravenous immunoglobulin (IVIg) for Clostridioides difficile infection (CDI) no longer features in treatment guidelines. However, IVIg is still used by some clinicians for severe or recurrent CDI (rCDI) cases. The main objective of this study was to investigate the efficacy of IVIg and to identify possible predictors of disease resolution post IVIg administration for patients with CDI. This retrospective observational cohort study of patients ≥2 years old hospitalised with severe, relapsing, or rCDI treated with IVIg therapy was performed in a large UK tertiary hospital between April 2018 and March 2023. Scanned electronic notes from patient admissions and clinical reporting systems were used to collect relevant data. In total, 20/978 patients diagnosed with CDI over the 5-year study were treated with IVIg. Twelve (60%) had hospital-onset CDI. Eleven of the twenty patients (55%) responded to treatment, with a mean of 8.6 (SD 10.7) days to disease resolution. Sixteen (80%) patients were treated for severe CDI and four (20%) for rCDI (n = 3) and relapsing CDI (n = 1). There were no statistically significant differences in possible independent predictors of disease resolution post IVIg administration between groups. There was an average of 6.2 (4.9) days to IVIg administration after diagnosis with no difference between responders and non-responders (p = 0.88) and no further significant difference in additional indicators. Four (36%) of the responders were immunosuppressed compared to just one (11%) of the non-responders (p = 0.15). Six of the responders (two with recurrent and four with severe CDI) improved rapidly within 2 days, and three of these were immunosuppressed. We observed disease resolution post IVIg therapy in over 50% of patients with refractory CDI. Our data also support a potential enhanced effect of IVIg in immunosuppressed individuals. Thus, the role of IVIg for CDI treatment, particularly in the immunosuppressed, warrants future case-control studies coupled to mechanistic investigations to improve care for this ongoing significant healthcare-associated infection.

Impact of time to treatment in first occurrence, non-severe Clostridioides difficile infection for elderly patients: are we waiting too long to treat?

Data evaluating timeliness of antibiotic therapy in Clostridioides difficile infections (CDI) are not well established. The study's purpose was to evaluate the impact of time-to-CDI treatment on disease progression. A case-control study was performed among hospitalized patients with CDI from 1/2018 to 2/2022. Inclusion criteria were age ≥65 years, first occurrence, non-severe CDI at symptom onset, and CDI treatment for ≥72 hours. Cases included patients who progressed to severe or fulminant CDI; controls were patients without CDI progression. Time to CDI treatment was evaluated in three ways: a classification and regression tree (CART)-defined threshold, time as a continuous variable, and time as a categorical variable. 272 patients were included; 136 with CDI progression, 136 patients without. The median (IQR) age was 74 (69-81) years, 167 (61%) were women, and 108 (40%) were immunosuppressed. CDI progression patients more commonly were toxin positive (66 [49%] vs 52 [38%], P = .087) with hospital-acquired disease (57 [42%] vs 29 [21%], P < 0.001). A CART-derived breakpoint for optimal time-to-CDI treatment of 64 hours established early (184, 68%) and delayed treatment (88, 32%). When accounting for confounding variables, delayed CDI treatment was associated with disease progression (adjOR, 4.6; 95%CI, 2.6-8.2); this was observed regardless of how time-to-CDI-active therapy was evaluated (continuous adjOR, 1.02; categorical adjOR, 2.11). Delayed CDI treatment was associated with disease progression and could represent an important antimicrobial stewardship measure with future evaluation.

673. Sniffing Out Adherence: Evaluation of a Clostridioides difficile guideline at a Tertiary Academic Medical Center

Abstract Background Tufts Medical Center’s (TMC) Antimicrobial Stewardship Team (AMT) in collaboration with gastroenterology (GI) developed an institutional treatment algorithm to guide appropriate inpatient management of Clostridioides difficile infection (CDI). The CD treatment algorithm was revised in April 2022 to reflect updated national clinical practice guidelines and disseminated to TMC providers. Our study aimed to assess provider compliance to TMC’s CD treatment algorithm. Methods A retrospective study of adult patients hospitalized from April 15, 2022 to October 31, 2022 and tested for CD was conducted. We collected patient demographics, white blood cell count, serum creatinine (SC), length of stay, CD treatment, Infectious Diseases (ID) &amp; GI consult, occurence of severe CDI (defined as white blood cell &amp;gt; 15 K/uL or SC &amp;gt; 1.5 mg/dL), occurrence of recurrent CDI, and immunocompromised status (defined by having had organ or bone marrow transplant, receiving immunomodulatory therapy or chronic steroids). A 2-step Clostridioides difficile (CD) testing algorithm was used. For CD toxin A/B &amp; glutamate dehydrogenase antigen (GDH) indeterminate results, reflex to nucleic amplification test (NAAT) was performed only with AMT approval. Results A total of 111 inpatients had CD toxin/GDH stool testing; 70 (63%) positive and 41 (37%) indeterminate. Of patients who had an indeterminate CD toxin/GDH, none had subsequent CD NAAT testing, and none receive CDI treatment. Of the others, 81 (73%), 23 (21%), and 7 (6%) were diagnosed with non-severe, severe, and fulminant CDI, respectively. The overall adherence to the institutional CD treatment algorithm was 58% (figure 1). More patients were appropriately treated with oral vancomycin (11, 65%) compared to those who were appropriately treated with fidaxomicin (9, 24%). Guidance adherence was (3) 38% among patients who had one or more recurrent episodes of CD, and none received suggested ID or GI consultation for additional CDI treatment consideration. Conclusion Adherence to institutional CD treatment algorithm was low. This study highlights opportunities to improve prescription of first line CDI therapy, especially among patients who are at higher risk for recurrence. Disclosures Maureen Campion, PharmD, BCIDP, Shinoigi: Speaker

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

Clostridioides difficile infection in neurosurgical patients in a national centre over 10 years: less common but associated with longer hospital stays.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea, contributing to patient morbidity and prolonged length-of-stay (LOS). We retrospectively assessed CDI over a decade in a national neurosurgical centre, with a multi-disciplinary approach to CDI surveillance and antimicrobial stewardship, by comparing CDI patients with other patient groups. Data on CDI in neurosurgical inpatients between January 2012 and December 2021 were collated. Disease-specific variables were compared to other inpatients with CDI. Rates per 10,000 bed days used were calculated. Patient-specific differences were compared with neurosurgical patients without CDI. CDI rates by patient group were explored using odds ratio (OR) and χ2 analyses. Negative binomial regression was used to investigate CDI rates over time. Of 50 neurosurgical patients with CDI, all were HA; the average age was 53 years (standard deviation (SD) 16.3 years), 49 were first-episode CDI, and three had severe CDI. The majority (76.7%) had received recent antimicrobials. Compared with non-neurosurgical CDI patients, neurosurgical CDI rates differed significantly (1.9 versus 3.6 per 10,000 bed days used, p < 0.05), neurosurgical patients were younger (p ≤ 0.01), C. difficile testing was more likely to be requested by neurosurgeons (OR 2.4; p ≤ 0.01), and the proportion of severe CDI was higher (6% versus 2%, OR 3.0, p = 0.07, confidence interval (CI) 0.54 to 11.3). Within the neurosurgical cohort, CDI patients had an average LOS four times that of other patients (CI 15.2 to 35.1; p < 0.01) and were older (53.5 versus 47.8 years, CI 0.1 to 11 years; p < 0.05). Only one CDI outbreak was linked to neurosurgical patients. CDI in neurosurgery patients differed from the wider hospital, with greater awareness of CDI testing. Longer LOS impacted bed utilisation with limited capacity. Robust surveillance supports proactive antimicrobial stewardship programmes in this vulnerable population.

Oral teicoplanin administration suppresses recurrence of Clostridioides difficile infection: Proof of concept

ObjectivesTeicoplanin is a potential antimicrobial candidate for Clostridioides difficile infection (CDI) treatment. However, the therapeutic potential of teicoplanin against severe CDI has not been clinically proven. In the present study, we investigated the efficacy of oral teicoplanin administration against severe CDI and the recurrence of severe CDI after teicoplanin treatment in a mouse model. MethodsA lethal CDI mouse model was established by colonizing the mice with C. difficile ATCC® 43255; they were orally administered teicoplanin (128 mg/kg/d) or vancomycin (160 mg/kg/d) for 10 d, 24 h after C. difficile spore challenge, and physiological and biological responses were monitored for 20 d after the initial antibiotic treatment. We also performed the in vitro time-kill assay and determined minimum inhibitory concentration (MIC), post-antibiotic effect, and toxin production with antibiotic exposure. ResultsThe therapeutic response (survival rates, body weight change, clinical sickness score grading, C. difficile load, and toxin titer in feces) of oral teicoplanin administration was comparable to that of oral vancomycin administration in the lethal CDI mouse model. Moreover, teicoplanin treatment suppressed the re-onset of diarrhea and re-increase in toxin titer 10 d after treatment compared with that by vancomycin treatment. In in vitro experiments, teicoplanin exhibited time-dependent antibacterial activity and possessed lower MIC and longer post-antibiotic effect than vancomycin against C. difficile. C. difficile toxin production was numerically lower with teicoplanin exposure than with vancomycin exposure. ConclusionsThe results obtained from the present basic experiments could suggest that teicoplanin is a potential antibiotic for the treatment of severe CDI with recurrence-prevention activity.

Derivation of clinical predictive factors (CHIEF) for first recurrent Clostridioides difficile infection

Current models for predicting Clostridioides difficile infection (CDI) recurrence rates have a limited capacity to account for important risk factors. This study developed a clinical prediction rule for CDI recurrence. This retrospective cohort study evaluated 209 patients with CDI at a university hospital in Japan. Logistic regression and receiver operating characteristic curve analyses were performed to identify potential predictors (age, sex, underlying diseases, antibiotic use, acid suppressants, immunosuppressants, CDI history) of CDI recurrence. Forty-five patients developed recurrent CDI. Univariate analyses identified several significant recurrence predictors (enteral feeding, inflammatory bowel diseases [IBD], community-onset CDI, severe CDI). Enteral feeding (odds ratio: 3.87, 95% confidence interval: 1.75-8.56) and IBD (odds ratio: 7.08, 95% confidence interval: 1.28-39.06) were significant factors in the multivariate analysis. The CHIEF predictive scoring system was developed using 5 relevant variables (carbapenem use, hematologic malignancy, IBD, enteral feeding, fluoroquinolone use); the area under the receiver operating characteristic curve for the CHIEF score was 0.70. The CHIEF score incorporates useful, clinically available factors and could help identify patients at risk of recurrent CDI. These findings contribute to the understanding of risk factors associated with CDI recurrence and provide support for the development of prevention strategies.