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Clostridioides difficile infection (CDI) is a complex disease that by virtue of both its initial virulence and proclivity toward recurrent episodes causes a high morbidity, mortality, and financial burden. This burden is felt by patients and their families as well as the U.S. healthcare system. Recurrent CDI episodes can occur in 25–65% of patients, with a cycle of multiple recurrences in a single patient contributing to the complexity of care. Patients with or suspected of having CDI will receive treatment and their care will be managed across multiple healthcare settings and will include many different levels of healthcare workers. The understanding of this infection is essential for all who are involved in the care of these patients. A well-structured and implemented Transition of Care process can ease the burden on the healthcare system, patients, and their families; reduce the cost of care; and improve patient outcomes. We review the development of Transitions of Care processes, resource guides, and their relevance to improving the management of CDI. [ABSTRACT FROM AUTHOR]

The pathogenesis of Clostridioides difficile infection (CDI) has largely been attributed to the action of two major toxins – A and B. An enhanced systemic humoral immune response against these toxins has been shown to be protective against recurrent CDI. Over the years, fully human monoclonal antibodies against both of these toxins have been developed in an attempt to counter the increasing incidence of recurrent CDI. Clinical trials conducted to evaluate the efficacy of anti-toxin A monoclonal antibody, actoxumab, and anti-toxin B monoclonal antibody, bezlotoxumab, demonstrated that bezlotoxumab substantially lowered the rate of recurrent infection, while actoxumab did not. A significant therapeutic benefit was appreciated in patients with at least one high-risk factor for recurrence, including, age ⩾65 years, immunocompromised state, prior CDI and severe CDI. In light of toxins A and B being immunogenic, vaccine trials are underway with the aim to prevent primary infection. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is a consequence of flagrant use of antibiotics, an aging population with increasing comorbidities, and increased hospitalizations. The treatment of choice for CDI is antibiotics (vancomycin or fidaxomicin), with a possibility of recurrent CDI despite lack of additional risk factors for CDI. For the last 10 years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, with success rates of over 85% compared with less than 50% with antibiotics for multiple recurrent CDI. Along with the success of FMT, several adverse and serious adverse events with FMT have been reported. These range from self-limiting abdominal pain to death due to severe sepsis. This review focuses on the safety of FMT, emphasizing the reports of transmission of pathobionts like extended-spectrum beta lactamase Escherichia coli and Shiga toxin-producing E. coli. The severe acute respiratory syndrome coronavirus-2 is a potential pathogen that could be transmitted via FMT during the COVID-19 pandemic. The challenges faced by clinicians for donor screening, clinical trials, and other aspects of FMT during the pandemic are discussed. [ABSTRACT FROM AUTHOR]

The pathogenesis of Clostridioides difficile infection (CDI) was recognized with its link to the use of antimicrobials. Antimicrobials significantly alter gut microbiota structure and composition, which led to the discovery of the association of this gut perturbation with the development of CDI. A number of factors implicated in its pathogenesis, such as advancing age, proton-pump inhibitors, and gastrointestinal diseases, are linked to gut microbiota perturbations. In an effort to better understand CDI, a multitude of studies have tried to ascertain protective and predictive microbial footprints linked with CDI. It has further been realized that CDI in itself can alter the gut microbiome. Its spore-forming capability poses as an impediment in the management of the infection and contributes to its recurrence. Antibiotic therapies used for its management have also been linked to gut microbiota changes, making its treatment a little more challenging. In an effort to exploit and utilize this association, gut microbial restoration therapies, particularly in the form of fecal microbial transplant, are increasingly being put to use and are proving to be beneficial. In this review, we summarize the association of the gut microbiome and microbial perturbation with initial and recurrent CDI. [ABSTRACT FROM AUTHOR]

Sehgal and Khanna11 review the relationship between this decreased immune response and CDI outcomes and how this has been translated to therapy for patients. It appears based on modeling studies that fidaxomicin may be the most cost-effective treatment strategy for an initial episode of nonsevere CDI and vancomycin for severe CDI, and fidaxomicin for a first recurrence and antibiotics followed by FMT for any subsequent episodes. A high incidence and severity of primary and recurrent I Clostridioides difficile i infection (CDI) continue to plague healthcare systems and people worldwide.[1] Prior to the coronavirus disease 2019 (COVID-19) pandemic, CDI was the most common infection seen in hospitals, and to date, it continues to be the most common bacterial infection in hospitals.[2] Targeting CDI by a multimodal approach by understanding its disease course, pathophysiology, appropriate treatment with benefits, and adverse events, health care delivery to be able to effectively administer treatments across care settings is paramount to curb the difficult menace that CDI is.[1] Therapeutic advances in gastroenterology have solicited and published articles as part of a special collection aiming to focus on the epidemiology, testing, management (antibiotic, antibody treatment, and microbiome-based therapies), the economic burden, and transitions of care aspects related to CDI. [Extracted from the article]

The pathogenesis of Clostridioides difficile infection (CDI) was recognized with its link to the use of antimicrobials. Antimicrobials significantly alter gut microbiota structure and composition, which led to the discovery of the association of this gut perturbation with the development of CDI. A number of factors implicated in its pathogenesis, such as advancing age, proton-pump inhibitors, and gastrointestinal diseases, are linked to gut microbiota perturbations. In an effort to better understand CDI, a multitude of studies have tried to ascertain protective and predictive microbial footprints linked with CDI. It has further been realized that CDI in itself can alter the gut microbiome. Its spore-forming capability poses as an impediment in the management of the infection and contributes to its recurrence. Antibiotic therapies used for its management have also been linked to gut microbiota changes, making its treatment a little more challenging. In an effort to exploit and utilize this association, gut microbial restoration therapies, particularly in the form of fecal microbial transplant, are increasingly being put to use and are proving to be beneficial. In this review, we summarize the association of the gut microbiome and microbial perturbation with initial and recurrent CDI. [ABSTRACT FROM AUTHOR]

The pathogenesis of Clostridioides difficile infection (CDI) has largely been attributed to the action of two major toxins – A and B. An enhanced systemic humoral immune response against these toxins has been shown to be protective against recurrent CDI. Over the years, fully human monoclonal antibodies against both of these toxins have been developed in an attempt to counter the increasing incidence of recurrent CDI. Clinical trials conducted to evaluate the efficacy of anti-toxin A monoclonal antibody, actoxumab, and anti-toxin B monoclonal antibody, bezlotoxumab, demonstrated that bezlotoxumab substantially lowered the rate of recurrent infection, while actoxumab did not. A significant therapeutic benefit was appreciated in patients with at least one high-risk factor for recurrence, including, age ⩾65 years, immunocompromised state, prior CDI and severe CDI. In light of toxins A and B being immunogenic, vaccine trials are underway with the aim to prevent primary infection. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is a consequence of flagrant use of antibiotics, an aging population with increasing comorbidities, and increased hospitalizations. The treatment of choice for CDI is antibiotics (vancomycin or fidaxomicin), with a possibility of recurrent CDI despite lack of additional risk factors for CDI. For the last 10 years, fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, with success rates of over 85% compared with less than 50% with antibiotics for multiple recurrent CDI. Along with the success of FMT, several adverse and serious adverse events with FMT have been reported. These range from self-limiting abdominal pain to death due to severe sepsis. This review focuses on the safety of FMT, emphasizing the reports of transmission of pathobionts like extended-spectrum beta lactamase Escherichia coli and Shiga toxin-producing E. coli. The severe acute respiratory syndrome coronavirus-2 is a potential pathogen that could be transmitted via FMT during the COVID-19 pandemic. The challenges faced by clinicians for donor screening, clinical trials, and other aspects of FMT during the pandemic are discussed. [ABSTRACT FROM AUTHOR]

Background: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower. Objectives: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs). Design: A systematic review and meta-analysis was conducted. Data Sources and Methods: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs). Results: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71–85%). There was significant heterogeneity among studies with an I 2 of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60–82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74–92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, p < 0.0001). Conclusions: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies. [ABSTRACT FROM AUTHOR]

Background: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower. Objectives: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs). Design: A systematic review and meta-analysis was conducted. Data Sources and Methods: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs). Results: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71–85%). There was significant heterogeneity among studies with an 퐼² of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60–82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74–92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, 푝 < 0.0001). Conclusions: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies. [ABSTRACT FROM AUTHOR]

The species composition of the human gut microbiota is related to overall health, and a healthy gut microbiome is crucial in maintaining colonization resistance against pathogens. Disruption of gut microbiome composition and functionality reduces colonization resistance and has been associated with several gastrointestinal and non-gastrointestinal diseases. One prime example is Clostridioides difficile infection (CDI) and subsequent recurrent infections that occur after the development of systemic antibiotic-related dysbiosis. Standard-of-care antibiotics used for both acute and recurrent infections do not address dysbiosis and often worsen the condition. Moreover, monoclonal antibodies, recommended in conjunction with standard-of-care antibiotics for the prevention of recurrent CDI in patients at high risk of recurrence, reduce recurrences but do not address the underlying dysbiosis. Fecal microbiota transplantation (FMT) is an evolving therapeutic strategy in which microbes are harvested from healthy donor stool and transplanted into the gut of a recipient to restore the gut microbiome. Although effective in the prevention of recurrent CDI, some existing challenges include screening and the standardization of stool acquisition and processing. Recent safety alerts by the US Food and Drug Administration raised concern about the possibility of transmission of multidrug-resistant organisms or severe acute respiratory syndrome coronavirus 2 via FMT. Increased knowledge that microbes are beneficial in restoring the gut microbiome has led to the clinical development of several newer biotherapeutic formulations that are more regulated than FMT, which may allow for improved restoration of the gut microbiome and prevention of CDI recurrence. This review focuses on mechanisms by which gut microbiome restoration could influence colonization resistance against the pathogen C. difficile. Plain language summary: The Role of the Gut Microbiome in Clostridioides difficile Infection Introduction: A rich and diverse gut microbiome is key to immune system regulation and colonization resistance against pathogens. A disruption in the gut microbiome composition can make the gut more vulnerable to diseases such as Clostridioides difficile infection (CDI), caused by the bacterium C. difficile. CDI management presents a therapeutic dilemma, as it is usually treated with antibiotics that can treat the infection but also can damage the microbiome. Treatment of CDI using antibiotics can further reduce microbial diversity and deplete beneficial bacteria from the gut leading to a condition called dysbiosis. Antibiotic treatment can be followed by therapies that restore the gut microbiota, boost colonization resistance, and prevent the development of antimicrobial resistance. It is important to evaluate treatment options to determine their safety and effectiveness. Methods: The researchers provided an overview of the mechanisms that the gut microbiome uses to prevent colonization of the gut by pathogens. They subsequently reviewed the efficacy and shortcomings of the following treatments for CDI: - Antibiotics - Monoclonal antibodies - Fecal microbiota transplantation (FMT) Results: Commensal intestinal bacteria prevent colonization of the gut by pathogens using mechanisms such as: - Competition for key nutrients - Production of inhibitory bile acids - Short-chain fatty acid production - Lowering the luminal pH - Production of bacteriocins Antibiotic therapy is recommended as a standard treatment for CDI. However, patients are vulnerable to recurrent CDI after discontinuation of the therapy. Monoclonal antibodies that inactivate C. difficile toxins may be recommended along with antibiotics to prevent recurrent CDI. However, this approach does not restore the microbiome. FMT is one method of microbial restoration, where stool is harvested from a healthy donor and transplanted into a patient's colon. Although FMT has shown some efficacy in the treatment of recurrent CDI, the procedure is not standardized. Safety concerns have been raised about the possibility of transmission of multidrug-resistant pathogens via FMT. Conclusion: Treatment methods that can efficiently restore the diversity of the gut microbiome are crucial in preventing recurrence of CDI. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI. [ABSTRACT FROM AUTHOR]

Background: Microbiota-based treatments reduce the incidence of recurrent Clostridioides difficile infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited. Objectives: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) – the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration – for preventing rCDI in adults. Design: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL. Methods: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively. Results: Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants). Conclusion: Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL. [ABSTRACT FROM AUTHOR]

Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available. Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes. Design: Retrospective cohort study. Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996–February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar's test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). p < 0.05 was considered statistically significant. Results: Overall, 101 cases and 100 controls (1997–2018) were included; median age 27 (range, 20–41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% (n = 16), during pregnancy: 51.5% (n = 52), and postpartum: 32.7% (n = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery (p = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization (p = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19–543.19; p = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04–0.99; p = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes. Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed. [ABSTRACT FROM AUTHOR]

Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment. Objectives: We aimed to assess histological changes over time. Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic. Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models. Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34–3.31, p = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34–3.02, p = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16–3.00, p = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19–0.83, p = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14–0.42, p < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47–1.05, p = 0.084). Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide. [ABSTRACT FROM AUTHOR]

Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment. Objectives: We aimed to assess histological changes over time. Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic. Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models. Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34-3.31, 푝 = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34-3.02, 푝 = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16-3.00, 푝 = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19-0.83, 푝 = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14-0.42, 푝 < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47-1.05, 푝 = 0.084). Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide. [ABSTRACT FROM AUTHOR]

Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available. Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes. Design: Retrospective cohort study. Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996–February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar’s test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). 푝 < 0.05 was considered statistically significant. Results: Overall, 101 cases and 100 controls (1997–2018) were included; median age 27 (range, 20–41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% (푛 = 16), during pregnancy: 51.5% (푛 = 52), and postpartum: 32.7% (푛 = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery (푝 = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization (푝 = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19–543.19; 푝 = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04–0.99; 푝 = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes. Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed. [ABSTRACT FROM AUTHOR]

Background: Microbiota-based treatments reduce the incidence of recurrent Clostridioides difficile infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited. Objectives: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) – the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration – for preventing rCDI in adults. Design: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL. Methods: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively. Results: Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants). Conclusion: Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile infection (CDI) is associated with poor outcomes in patients with inflammatory bowel diseases (IBD). Objectives: We conducted a nationally representative cohort study to evaluate the impact of recurrent CDI (rCDI)-related hospitalization on longitudinal unplanned healthcare utilization in patients with IBD. Design: This was a retrospective cohort study that utilized the 2017 Nationwide Readmissions Database (NRD). Methods: We identified 13,446 patients with IBD, hospitalized at least twice from January to June 2017 and followed through December 2017; of these, 1,148 had CDI-related hospitalizations. We compared the annual burden of hospitalization and IBD-related surgery in IBD patients with rCDI-related admission versus single CDI-related admission (primary reference), and those with one or more CDI-related admission versus no CDI-related admission (secondary reference). Results: There were no significant differences in risk and burden of unplanned healthcare utilization (time spent in-hospital, 27 days versus 27 days, p = 0.62), 6-month readmission (63% versus 64.3%, p = 0.8) or IBD-related surgery in patients with recurrent (two or more) CDI-related hospitalizations versus single CDI-related admission. However, patients with ⩾1 CDI-related admission versus no CDI admissions experienced higher rate of 6-month readmission (61.1% versus 55.7%, p <.001), total days spent in the hospital per year (median: 26 days versus 21 days, p <.001), total cost across all hospitalizations per year ($212,524 versus $184,384, p < 0.01), and inpatient mortality (3.28% versus 1.81%, p = 0.01), without an increase in risk of IBD-related surgery (6.7% versus 6.4%, p = 0.79). Conclusion: While patients with IBD hospitalized for CDI have poor longitudinal inpatient outcomes, recurrent admissions for CDI may not increase risk of adverse outcomes compared to one-time admission. [ABSTRACT FROM AUTHOR]

Background: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic. Objectives: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID. Design: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed. Data Sources and Methods: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages 'meta' and 'metafor'. Results: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06–0.22, I 2 = 99%] and 0.22 (95% CI, 0.10–0.41, I 2 = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04–0.38, I 2 = 96%), 0.06 (95% CI, 0.03–0.11, I 2 = 98%), 0.20 (95% CI, 0.08–0.43, I 2 = 98%), and 0.17 (95% CI, 0.10–0.27, I 2 = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04–0.23, I 2 = 98%), 0.20 (95% CI, 0.06–0.50, I 2 = 97%), and 0.17 (95% CI, 0.06–0.37, I 2 = 96%), respectively. Conclusion: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review. [ABSTRACT FROM AUTHOR]

Background: Polymerase chain reaction (PCR) is a sensitive test for diagnosing Clostridioides difficile infection (CDI) and could remain positive following resolution of CDI. The kinetics of PCR positivity following antibiotics for CDI is unknown. We studied this and whether it predicted CDI recurrence. Methods: Adults with CDI from October 2009 to May 2017 were included. Serial stool samples within 60 days of treatment were collected. Recurrent CDI was defined as diarrhea after interim symptom resolution with positive stool PCR within 56 or 90 days of treatment completion. Contingency table analysis was used to assess the risk of recurrence. Results: Fifty patients were included [median age: 51 (range = 20–86) years, 66% women]. Treatment given was metronidazole, 50% (25); vancomycin, 44% (22); both, 4% (2); and fidaxomicin, 2% (1). Median duration of treatment for all 50 patients was 14 (range = 8–60) days. The median duration of treatment in patients who got prolonged therapy (>14 days) (n = 10) was 47 (range = 18–60) days. Median time to negative PCR was 9 (95% CI, 7–14) days from treatment initiation, which did not differ by antibiotics given (p = 0.5). A positive PCR during or after treatment was associated with a higher risk of recurrence at 56 days (p = 0.02) and at 90 days (p = 0.009). Conclusion: The median time to negative PCR in CDI was 9 days from treatment initiation. The PCR positivity during or after treatment may be useful for recurrence prediction; larger studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridioides difficile infection (CDI) with an increased risk of adverse outcomes including increased in-hospital mortality, IBD treatment failure, re-hospitalization, and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors [body mass index (BMI), statin use, opioid use, and antidepressant use] on CDI risk and adverse outcomes in these patients. Methods: Using a retrospective design, variables were abstracted from records for patients with IBD and CDI from 2008 to 2013. Statistical analysis comprised descriptive statistics and univariate and multivariate logistic regression analyses. Results: There were 137 patients with IBD and CDI included in this study. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe, complicated CDI, compared with 22% of patients in the underweight/normal BMI [odds ratio (OR) 2.85, p = 0.02] and 19% in the obese category (OR 3.95, p = 0.04). Statin use was associated with severe or severe, complicated CDI when controlling for age and BMI (OR 5.66, p = 0.01). There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Conclusions: An overweight BMI and statin use were associated with severe or severe, complicated CDI in IBD patients. Further studies are needed to better understand how these factors impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of complications from CDI. [ABSTRACT FROM AUTHOR]

Background: Prevention of recurrent Clostridioides difficile infection (CDI) is a challenge in clinical practice, particularly in patients who need systemic antimicrobial therapy. We aimed to evaluate the role of oral vancomycin prophylaxis (OVP) in prevention of primary or future CDI in patients on systemic antimicrobial therapy. Methods: A systematic search of MEDLINE, Embase, and Web of Science was performed from 2000 to January 2020. We included case-control or cohort studies that included patients on systemic antimicrobial therapy who did or did not receive oral vancomycin prophylaxis (OVP) and were evaluated for development of CDI. Odds ratio (OR) estimates with 95% confidence intervals (CI) were calculated. Results: Four studies including 1352 patients evaluated OVP for primary CDI prevention, with CDI occurring in 29/402 patients on OVP (7.4%) compared with 10.4% (99/950) without OVP. Meta-analysis revealed no significant decrease in risk of CDI in patients who received OVP (OR, 0.18; 95% CI, 0.03–1.03; p = 0.06). There was significant heterogeneity with I 2 = 76%. Ten studies including 9258 patients evaluated OVP for secondary CDI prevention. Future CDI occurred in 91/713 patients on OVP (13.3%) compared with 21.9% (1875/8545) who did not receive OVP. Meta-analysis revealed a statistically significant decreased risk of future CDI (OR, 0.34; 95% CI, 0.20–0.59; p < 0.00001). Significant heterogeneity was seen with I 2 = 59%. Discussion: Based on observational data, OVP appears to decrease the risk of future CDI in patients with prior CDI who require systemic antimicrobial therapy. However, OVP was not effective for primary prevention of CDI. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridioides difficile infection (CDI) with an increased risk of adverse outcomes including increased in-hospital mortality, IBD treatment failure, re-hospitalization, and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors [body mass index (BMI), statin use, opioid use, and antidepressant use] on CDI risk and adverse outcomes in these patients. Methods: Using a retrospective design, variables were abstracted from records for patients with IBD and CDI from 2008 to 2013. Statistical analysis comprised descriptive statistics and univariate and multivariate logistic regression analyses. Results: There were 137 patients with IBD and CDI included in this study. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe, complicated CDI, compared with 22% of patients in the underweight/normal BMI [odds ratio (OR) 2.85, p = 0.02] and 19% in the obese category (OR 3.95, p = 0.04). Statin use was associated with severe or severe, complicated CDI when controlling for age and BMI (OR 5.66, p = 0.01). There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Conclusions: An overweight BMI and statin use were associated with severe or severe, complicated CDI in IBD patients. Further studies are needed to better understand how these factors impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of complications from CDI. [ABSTRACT FROM AUTHOR]

Background: Prevention of recurrent Clostridioides difficile infection (CDI) is a challenge in clinical practice, particularly in patients who need systemic antimicrobial therapy. We aimed to evaluate the role of oral vancomycin prophylaxis (OVP) in prevention of primary or future CDI in patients on systemic antimicrobial therapy. Methods: A systematic search of MEDLINE, Embase, and Web of Science was performed from 2000 to January 2020. We included case-control or cohort studies that included patients on systemic antimicrobial therapy who did or did not receive oral vancomycin prophylaxis (OVP) and were evaluated for development of CDI. Odds ratio (OR) estimates with 95% confidence intervals (CI) were calculated. Results: Four studies including 1352 patients evaluated OVP for primary CDI prevention, with CDI occurring in 29/402 patients on OVP (7.4%) compared with 10.4% (99/950) without OVP. Meta-analysis revealed no significant decrease in risk of CDI in patients who received OVP (OR, 0.18; 95% CI, 0.03–1.03; p = 0.06). There was significant heterogeneity with I 2 = 76%. Ten studies including 9258 patients evaluated OVP for secondary CDI prevention. Future CDI occurred in 91/713 patients on OVP (13.3%) compared with 21.9% (1875/8545) who did not receive OVP. Meta-analysis revealed a statistically significant decreased risk of future CDI (OR, 0.34; 95% CI, 0.20–0.59; p < 0.00001). Significant heterogeneity was seen with I 2 = 59%. Discussion: Based on observational data, OVP appears to decrease the risk of future CDI in patients with prior CDI who require systemic antimicrobial therapy. However, OVP was not effective for primary prevention of CDI. [ABSTRACT FROM AUTHOR]

Background: Polymerase chain reaction (PCR) is a sensitive test for diagnosing Clostridioides difficile infection (CDI) and could remain positive following resolution of CDI. The kinetics of PCR positivity following antibiotics for CDI is unknown. We studied this and whether it predicted CDI recurrence. Methods: Adults with CDI from October 2009 to May 2017 were included. Serial stool samples within 60 days of treatment were collected. Recurrent CDI was defined as diarrhea after interim symptom resolution with positive stool PCR within 56 or 90 days of treatment completion. Contingency table analysis was used to assess the risk of recurrence. Results: Fifty patients were included [median age: 51 (range = 20–86) years, 66% women]. Treatment given was metronidazole, 50% (25); vancomycin, 44% (22); both, 4% (2); and fidaxomicin, 2% (1). Median duration of treatment for all 50 patients was 14 (range = 8–60) days. The median duration of treatment in patients who got prolonged therapy (>14 days) (n = 10) was 47 (range = 18–60) days. Median time to negative PCR was 9 (95% CI, 7–14) days from treatment initiation, which did not differ by antibiotics given (p = 0.5). A positive PCR during or after treatment was associated with a higher risk of recurrence at 56 days (p = 0.02) and at 90 days (p = 0.009). Conclusion: The median time to negative PCR in CDI was 9 days from treatment initiation. The PCR positivity during or after treatment may be useful for recurrence prediction; larger studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

Background: The incidence of Clostridioides difficile infection (CDI) is increasing in the general population. Data on the epidemiology of CDI in peripartum women – a highly vulnerable patient population – is scarce. The objective of this study was to report the incidence of CDI in peripartum women. Methods: A single-center retrospective cohort study was conducted in peripartum women from 1997 to 2017. Peripartum CDI was defined as definite CDI (watery diarrhea for >24 h with positive stool assay) during pregnancy, or within 6 weeks postpartum. Incidence was reported per 100,000 pregnancies and time trends in incidence were analyzed using Poisson regression. Analyses were done separately for time trends before and after 2007, when CDI testing strategy changed to polymerase chain reaction. Results: From 1997 to 2017, 80 patients with peripartum CDI (47 during pregnancy, 33 postpartum) out of 125,683 pregnancies (0.064%) were identified. Incidence of CDI increased 3.4 fold (95% confidence interval 1.5–7.4, p = 0.005) over the 21 year period. Time trends were evident after (p = 0.054), but not before 2007 (p = 0.97). Conclusion: Incidence of CDI in peripartum women increased over the 21 year study period. The rise in incidence is concerning, and calls for heightened surveillance for CDI in this highly vulnerable population. [ABSTRACT FROM AUTHOR]

Background: The incidence of Clostridioides difficile infection (CDI) is increasing in the general population. Data on the epidemiology of CDI in peripartum women – a highly vulnerable patient population – is scarce. The objective of this study was to report the incidence of CDI in peripartum women. Methods: A single-center retrospective cohort study was conducted in peripartum women from 1997 to 2017. Peripartum CDI was defined as definite CDI (watery diarrhea for >24 h with positive stool assay) during pregnancy, or within 6 weeks postpartum. Incidence was reported per 100,000 pregnancies and time trends in incidence were analyzed using Poisson regression. Analyses were done separately for time trends before and after 2007, when CDI testing strategy changed to polymerase chain reaction. Results: From 1997 to 2017, 80 patients with peripartum CDI (47 during pregnancy, 33 postpartum) out of 125,683 pregnancies (0.064%) were identified. Incidence of CDI increased 3.4 fold (95% confidence interval 1.5–7.4, p = 0.005) over the 21 year period. Time trends were evident after (p = 0.054), but not before 2007 (p = 0.97). Conclusion: Incidence of CDI in peripartum women increased over the 21 year study period. The rise in incidence is concerning, and calls for heightened surveillance for CDI in this highly vulnerable population. [ABSTRACT FROM AUTHOR]