Recurrent Clostridium Difficile Infection Research Articles

Evaluation of an Oral Vancomycin Capsule for the Treatment of Clostridioides difficile Infections in an Academic Medical Center in Thailand

Background: The oral capsule formulation of vancomycin (Vancin-S) recently became available in Thailand; therefore, information on its effectiveness and safety in treating Clostridioides difficile infection (CDI) has not been available. Objective: To evaluate CDI outcomes and to access safety at the HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) following recommended oral vancomycin capsule treatment. Materials and Methods: Retrospective review of MSMC patients prescribed oral vancomycin capsule between December 1, 2022 and August 31, 2023. Inclusion and exclusion criteria were applied, analyzing CDI outcomes post- oral vancomycin capsule treatment and within 90 days thereafter. Safety of oral vancomycin capsule usage was also assessed. Results: Of the 41 patients prescribed oral vancomycin capsule, 13 met inclusion criteria and did not meet with exclusion criteria. There were eight definite and five probable CDI cases, with 12 initial treatments and one initial fulminant treatment. The incidence of CDI in the MSMC was 21.33 person-year. Clinical improvements were observed by the tenth day, with one patient experiencing residual symptoms, subsequently testing negative for CDI. All patients were cured. The oral vancomycin capsule treatments were well-tolerated without significant adverse effects. No CDI recurrence was detected among 12 cases followed up within 90 days post-treatment. Conclusion: The oral vancomycin capsule demonstrates safety and potential efficacy for CDI treatment in Thailand. Keywords: Oral vancomycin; Clostridioides difficile infection; Thailand

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Current and future microbiome-based therapies in inflammatory bowel disease.

The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis. This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use. The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.

Expression of Concern: Clostridium transplantifaecale sp. nov., a new bacterium isolated from patient with recurrent Clostridium difficile infection

Expression of Concern: Clostridium transplantifaecale sp. nov., a new bacterium isolated from patient with recurrent Clostridium difficile infection

Donor screening for fecal microbiota transplantation with a direct stool testing-based strategy: a prospective cohort study

Fecal microbiota transplantation (FMT) is effective against recurrent Clostridioides difficile infection (rCDI), but its safety is jeopardized by the potential transmission of pathogens, so international guidelines recommend either a quarantine or a direct stool testing. Whereas reports of the quarantine-based approach are emerging, data on the direct testing-based approach are not available. Our aim is to report outcomes of a donor screening framework for FMT including direct stool testing.In this prospective cohort study, all donor candidates recruited at our FMT centre underwent a four-step screening process to be enrolled as actual donors. Each collected stool donation was then evaluated with a direct stool testing including a molecular assay for gut pathogens and a culture assay for multi-drug resistant organisms (MDRO).From January 2019 to June 2023, 72 of 227 candidates (32%) were considered eligible and provided 277 stool donations. Ninety-nine donations (36%) were discarded for positivity to intestinal pathogens, most commonly enteropathogenic Escherichia coli (n = 37) and Blastocystis hominis (n = 20). Overall, 337 stool aliquots were obtained from 165 approved donations. All suspensions were used for patients with rCDI, and no serious adverse events or clinically evident infections were observed at 12 weeks after procedures.In our study, screening of donor faeces including direct stool testing led to the discard of a considerable rate of stool donations but was also extremely safe. This approach may represent a reliable strategy to guarantee the safety of FMT programs, especially in countries with high prevalence of MDRO.

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.

Efficacy, Safety, and Cost-effectiveness of Bezlotoxumab in Preventing Recurrent Clostridioides difficile Infection : Systematic Review and Meta-analysis.

Clostridioides difficile infection (CDI) remains a global health challenge. Bezlotoxumab (BEZ) is a monoclonal antibody against C. difficile toxin B. Two randomized controlled trials (RCTs), MODIFY I and II, confirmed BEZ efficacy in preventing recurrent Clostridioides difficile infection (rCDI). However, there are safety concerns about its use in patients with a history of congestive heart failure. Observational studies have since been conducted, and it is important to explore the consistency of BEZ efficacy, cost-effectiveness, and its safety utilizing these real-world data. We performed a systematic review and meta-analysis to pool the rate of rCDI in patients receiving BEZ and explore its efficacy and safety in preventing rCDI compared with control. We searched PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through April 2023 for relevant RCTs or observational studies assessing BEZ in preventing rCDI. Single-arm studies describing experience with BEZ in preventing rCDI were also included for proportion meta-analysis. A proportion meta-analysis with a random-effects model was used to pool the rCDI rate with its corresponding 95% CI. In a meta-analysis of efficacy, we generated the relative risk (RR) to compare BEZ versus control in preventing rCDI. Thirteen studies including 2 RCTs and 11 observational studies totaling 2337 patients, of which 1472 received BEZ, were included in the analysis. Of the constituent studies, 5 (1734 patients) compared BEZ versus standard-of-care (SOC). Pooled rate of rCDI in patients receiving BEZ was 15.8% (95% CI: 14%-17.8%), and was 28.9% (95% CI: 24%-34.4%) in the SOC. BEZ significantly reduced rCDI risk compared with SOC [RR=0.57 (95% CI: 0.45-0.72, I2 =16%)]. There was no difference in the overall mortality or heart failure risk. Of the 9 included cost-effectiveness analyses, 8 demonstrated BEZ+SOC cost-effectiveness compared with SOC alone. Our meta-analysis comprising real-world data revealed lower rCDI in patients receiving BEZ and supported its efficacy and safety when added to SOC therapy. The results were consistent across various subgroups. Available cost-effectiveness analyses mostly support BEZ+SOC cost-effectiveness compared with SOC alone.

The impact of existing total anti-toxin B IgG immunity in outcomes of recurrent Clostridioides difficile infection

Late anti-toxin-B humoral immunity acquired after treatment is important for preventing recurrent Clostridioides difficile infection. We prospectively-measured anti-toxin-B IgG and neutralization titers at diagnosis as potential early predictors of recurrence. High anti-toxin-B-IgG/neutralizing antibodies were associated with short-lasting protection within 6-weeks, however, no difference in recurrence risk was observed by 90-days post-infection.

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.

Lyophilized fecal microbiome transfer for primary Clostridioides difficile infection: a multicenter randomized controlled trial (DONATE Study)

Background Primary Clostridioides difficile infection (pCDI) carries high recurrence and mortality rates and is globally spread. pCDI is often a consequence of exposure to antibiotics, disrupting the healthy intestinal microbiota composition. Not surprisingly, in this antibiotic-associated infection, failure of the standard antibiotic treatment is high. Frozen fecal microbiota transplantation (FMT), the introduction of the microbial community from a healthy donor, has been shown to be safe and highly effective in cases of recurrent CDI, reaching >90% cumulative success rate. Importantly, FMT has shown potential for intestinal decolonization of multidrug-resistant organisms (MDRO), and/or mitigation of their ability to cause invasive infection. The use of FMT for pCDI, has been tested in small studies, showing promising results. The use of frozen FMT graft is often administered via colonoscopy or enteral (naso-jejunal) tubes, which are invasive procedures, placing significant burden on these often frail patients and the institutions providing the services. Moreover, frozen FMT is hampered by storage needs which limit accessibility and spread. Methods We have developed a lyophilized FMT product (Lyo-FMT - a dry compound that does not need freezing) that retains viability, prolongs the shelf time of the product and improves patient acceptance. In a randomized controlled multicenter trial, we aim to assess the efficacy of Lyo-FMT for pCDI in comparison to standard antibiotic therapy. Expected results This easy-to-administer product will restore the microbial community, fight the infective agent and reduce the overall antibiotic-resistant gene burden. This, in turn, will lower the recurrence rate and decrease carriage of other MDRO, coupled with a reduction in antibiotic use. Data on microbial shifts during treatment will shed light on our understanding of the pathophysiology of the disease. Clinicaltrials.gov registration NCT05709184, 2023-02-24

Standards for fecal microbiota transplant: Tools and therapeutic advances

Fecal microbiota transplantation (FMT) has been demonstrated to be efficacious in preventing recurrent Clostridioides difficile (C. difficile) infections, and is being investigated for treatment of several other diseases including inflammatory bowel disease, cancer, obesity, liver disease, and diabetes. To speed up the translation of FMT into clinical practice as a safe and standardized therapeutic intervention, additional evidence-based technical and regulatory guidance is needed. To this end in May of 2022, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a second webinar to discuss key issues still impeding the advancement and standardization of FMT. The goal of this two-day webinar was to provide a forum for scientific experts to share and discuss data and key challenges with one another. Discussion included a focus on the evaluation of safety, efficacy, clinical trial design, reproducibility and accuracy in obtained microbiome measurements and data reporting, and the potential for standardization across these areas. It also focused on increasing the application potential and visibility of FMT beyond treating C. difficile infections.

Systemic neutrophil degranulation and emergency granulopoiesis in patients with Clostridioides difficile infection

ObjectivesClostridioides difficile infection (CDI) is characterized by neutrophilia in blood, with a high leukocyte count accompanying severe infection. In this study, we characterized peripheral blood neutrophil activation and maturity in CDI by (i) developing a method to phenotype stored neutrophils for disease-related developmental alterations and (ii) assessing neutrophil-associated biomarkers. MethodsWe stored fixed leukocytes from blood collected within 24 h of diagnosis from a cohort of hospitalized patients with acute CDI. Additional study cohorts included recurrent CDI patients at time of and two months after FMT therapy and a control healthy cohort. We assessed levels of neutrophil surface markers CD66b, CD11b, CD16 and CD10 by flow cytometry. Plasma neutrophil elastase and lipocalin-2 were measured using ELISA, while G-CSF, GM-CSF and cytokines were measured using O-link Proteomic technology. ResultsCD66b+ neutrophil abundance assessed by flow cytometry correlated well with complete blood counts, establishing that neutrophils in stored blood are sufficiently well-preserved for phenotyping by flow cytometry. Neutrophil abundance was significantly increased in CDI patients compared to healthy controls. Emergency granulopoiesis in acute CDI patients was evidenced by lower neutrophil surface expression of CD10, CD11b and CD16. CD10+ staining of neutrophils started to recover within 3–7 days of CDI treatment. Neutrophil activation and degranulation were higher in acute CDI as assessed by plasma neutrophil elastase and lipocalin-2. Biomarker levels in immunocompetent subjects were associated with recurrence and fatal outcomes. ConclusionsNeutrophil activation and emergency granulopoiesis characterize the early immune response in acute CDI, with plasma degranulation biomarkers predictive of disease severity.

Outcomes After Fecal Microbiota Transplantation in Combination With Bezlotoxumab for Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection.

Fecal microbiota transplantation (FMT) prevents recurrent Clostridioides difficile infections (rCDI) in patients with inflammatory bowel disease. Bezlotoxumab is also indicated to prevent rCDI. We assess the impact of FMT in combination with bezlotoxumab in patients with inflammatory bowel disease and rCDI. We conducted a multicenter randomized placebo-controlled trial. All received a single colonoscopic FMT. Patients were randomized 1:1 to receive bezlotoxumab or placebo. Sixty-one patients were enrolled (30 received treatment and 31 received placebo). Overall, 5 participants (8%) experienced a CDI recurrence; 4 in the treatment arm, 1 in the placebo arm (13% vs 3%, P = 0.15). There was no clear benefit to the combination approach compared with FMT alone.

Management and Outcomes of Patients at a Specialty Clinic for Clostridioides difficile Infection.

Vancomycin and fidaxomicin taper regimens were the most common treatment strategies employed but nearly half of patients (40/83) referred to our Clostridioides difficile infection (CDI) clinic did not require further treatment. The overall 60-day CDI recurrence rate was 16.9% (11/65). CDI management at a dedicated clinic may improve clinical outcomes.

A review of fecal microbiota, live-jslm for the prevention of recurrent Clostridioides difficile infection.

To review the composition, preparation, proposed mechanism of action, safety, efficacy, and current place in therapy of Rebyota (fecal microbiota, live-jslm). As the first agent in a new class of drugs, live biotherapeutic products (LBPs), fecal microbiota, live-jslm offers another therapeutic approach for the prevention of recurrent Clostridioides difficile infection (rCDI). LBPs are given following antibiotic therapy for C. difficile to reintroduce certain bacteria present in the normal microbiome, as a means to reconstitute the microbiome of infected individuals. This review provides a summary of phase 2 and 3 clinical trials, product information, discussion of data limitations, and recommendations for place in therapy. High efficacy rates compared to placebo with sustained response up to 24 months after administration have been reported. The majority of adverse events identified were mild to moderate without significant safety signals. Fecal microbiota, live-jslm has consistently been shown in randomized trials to be safe and effective in reducing rCDI. Its approval marks the culmination of decades of work to identify, characterize, and refine the intestinal microbiome to create pharmaceutical products.

Enhancing bezlotoxumab binding to C. difficile toxin B2: insights from computational simulations and mutational analyses for antibody design

Clostridioides difficile infection (CDI) is a significant concern caused by widespread antibiotic use, resulting in diarrhea and inflammation from the gram-positive anaerobic bacterium C. difficile. Although bezlotoxumab (Bez), a monoclonal antibody (mAb), was developed to address CDI recurrences, the recurrence rate remains high, partly due to reduced neutralization efficiency against toxin B2. In this study, we aimed to enhance the binding of Bez to C. difficile toxin B2 by combining computational simulations and mutational analyses. We identified specific mutations in Bez, including S28R, S31W/K, Y32R, S56W and G103D/S in the heavy chain (Hc), and S32F/H/R/W/Y in the light chain (Lc), which significantly improved binding to toxin B2 and formed critical protein-protein interactions. Through molecular dynamics simulations, several single mutations, such as HcS28R, LcS32H, LcS32R, LcS32W and LcS32Y, exhibited superior binding affinities to toxin B2 compared to Bez wild-type (WT), primarily attributed to Coulombic interactions. Combining the HcS28R mutation with four different mutations at residue LcS32 led to even greater binding affinities in double mutants (MTs), particularly HcS28R/LcS32H, HcS28R/LcS32R and HcS28R/LcS32Y, reinforcing protein–protein binding. Analysis of per-residue decomposition free energy highlighted key residues contributing significantly to enhanced binding interactions, emphasizing the role of electrostatic interactions. These findings offer insights into rational Bez MT design for improved toxin B2 binding, providing a foundation for developing more effective antibodies to neutralize toxin B2 and combat-related infections. Communicated by Ramaswamy H. Sarma

Successful Treatment of Recurrent Clostridioides difficile Infection Using a Novel, Drinkable, Oral Formulation of Fecal Microbiota.

Fecal microbiota transplants can be administered orally in encapsulated form or require invasive procedures to administer liquid formulations. There is a need for an oral liquid formulation of fecal microbiota for patients who are unable to swallow capsules, especially if they require multiple, repeated administrations. These studies were conducted to develop a protocol to manufacturean organoleptically acceptable powdered fecal microbiota formulation that can be suspended in a liquid carrier and used for fecal microbiota transplantation. Several processing steps were investigated, including extra washes of microbiota prior to lyophilization and an addition of a flavoring agent. The viability of bacteria in the transplant formulation was tested using live/dead microscopy staining and engraftment into antibiotic-treated mice. After development of a clinical protocol for suspension of the powdered microbiota, the new formulation was tested in three elderly patients with recurrent Clostridioides difficile infections and who have difficulties in swallowing capsules. Changes in the microbial community structure in one of the patients were characterized using 16S rRNA gene profiling and engraftment analysis. The processing steps used to produce an organoleptically acceptable suspension of powdered fecal microbiota did not result in loss of its viability. The powder could be easily suspended in a liquid carrier. The use of the new formulation was associated with abrogation of the cycle of C. difficile infection recurrences in the three patients. We developed a novel organoleptically acceptable liquid formulation of fecal microbiota that is suitable for use inclinical trials for patients with difficulties in swallowing capsules.

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.

Characteristics of Patients With Initial Clostridioides difficile Infection (CDI) That Are Associated With Increased Risk of Multiple CDI Recurrences.

Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). iCDI was defined as a positive C difficile test in any clinical setting during January 2018-August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55-2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48-3.51), hospitalization (aOR, 1.64; 95% CI, 1.33-2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18-3.23) in the 12 weeks preceding iCDI were associated with mrCDI. Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs.

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.