scholarly journals Real-world Experience of Bezlotoxumab for Prevention of Clostridioides difficile Infection: A Retrospective Multicenter Cohort Study

2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Richard L Hengel ◽  
Timothy E Ritter ◽  
Ramesh V Nathan ◽  
Lucinda J Van Anglen ◽  
Claudia P Schroeder ◽  
...  
Keyword(s):  
Real World ◽  
Standard Of Care ◽  
The United States ◽  
Study Cohort ◽  
Multicenter Cohort Study ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Comorbidity Index ◽  
Clinical Trial Results ◽  
Successful Prevention

Abstract Background Bezlotoxumab is approved for prevention of recurrence of Clostridioides difficile infection (CDI) in adults receiving standard of care (SoC) therapy based on findings from MODIFY clinical trials. However, utilization practices and validation of trial results in the real world are limited. Methods Records of patients receiving bezlotoxumab between April 2017 and December 2018 across 34 infusion centers in the United States were retrospectively reviewed. Recurrent CDI (rCDI), defined as diarrhea lasting ≥2 days resulting in treatment, was assessed 90 days postbezlotoxumab. Results The study cohort included 200 patients (median age, 70 years; 66% female; median Charlson comorbidity index, 5), of whom 86% (n = 173) had prior CDI episodes and 79% (n = 158) had ≥2 risk factors for rCDI. SoC antibiotics included vancomycin (n = 137, 68%), fidaxomicin (n = 60, 30%), and metronidazole (n = 3, 2%). Median time from C. difficile stool test to bezlotoxumab and initiation of SoC to bezlotoxumab were 15 days and 11 days, respectively. Within 90 days, 31 of 195 patients (15.9%) experienced rCDI, which corresponds to a success rate of 84.1%. Patients with ≥2 CDI recurrences prebezlotoxumab had a higher risk of subsequent rCDI compared with those with 1 recurrence or primary CDI (hazard ratio, 2.77; 95% confidence interval, 1.14–6.76; P = .025). Conclusions This real-world multicenter study demonstrated successful prevention of rCDI with bezlotoxumab comparable to clinical trial results regardless of type of SoC and timing of infusion. Multiple prior CDI recurrences were associated with a higher risk of subsequent rCDI, supporting the use of bezlotoxumab earlier in the disease course.

scholarly journals Assessment of Kidney Injury as a Severity Criteria for Clostridioides Difficile Infection

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Travis J Carlson ◽  
Anne J Gonzales-Luna ◽  
Kimberly Nebo ◽  
Hannah Y Chan ◽  
Ngoc-Linh T Tran ◽  
...  
Keyword(s):  
Severe Disease ◽  
Kidney Injury ◽  
Relative Increase ◽  
Classification Criteria ◽  
Study Cohort ◽  
Multicenter Cohort Study ◽  
Clostridioides Difficile ◽  
Severity Classification ◽  
Threshold Criterion ◽  
Clostridioides Difficile Infection

Abstract Background The Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) revised their Clostridioides difficile infection (CDI) severity classification criteria in 2017 to include an absolute serum creatinine (SCr) value above a threshold (≥1.5 mg/dL) rather than a relative increase from baseline (≥1.5 times the premorbid level). To date, how to best define kidney injury as a CDI disease severity marker has not been validated to assess severe outcomes associated with CDI. Methods This multicenter cohort study included adult hospitalized patients with CDI. Patients were assessed for the presence of acute kidney injury (AKI), chronic kidney disease (CKD), and CDI severity using the 2010 and 2017 IDSA/SHEA CDI guidelines. Primary outcome was all-cause inpatient mortality. Results The final study cohort consisted of 770 CDI episodes from 705 unique patients aged 65 ± 17 years (female, 54%; CKD, 36.5%; AKI, 29.6%). Eighty-two episodes (10.6%) showed discordant severity classification results due to the inclusion of more patients with preexisting CKD in the severe disease category using an absolute SCr threshold criterion. The absolute SCr criterion better correlated with all-cause mortality (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.76–9.28; P = .001) than the relative increase in SCr (OR, 1.34; 95% CI, 0.62–2.89; P = .46). This corresponded to an increased likelihood of the 2017 CDI severity classification criteria to predict mortality (OR, 5.33; 95% CI, 1.81–15.72; P = .002) compared with the 2010 criteria (OR, 2.71; 95% CI, 1.16–6.32; P = .02). Conclusions Our findings support the 2017 IDSA/SHEA CDI severity classification criteria of a single pretreatment SCr in future CDI guideline updates.

scholarly journals Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Rosa Escudero-Sánchez ◽  
María Ruíz-Ruizgómez ◽  
Jorge Fernández-Fradejas ◽  
Sergio García Fernández ◽  
María Olmedo Samperio ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Recurrence Rates ◽  
Factors Associated ◽  
Clostridioides Difficile ◽  
Multicentre Cohort Study ◽  
Clostridioides Difficile Infection ◽  
Prevention Of Recurrence ◽  
Multicentre Cohort

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

scholarly journals Fecal microbiota transplantation increases colonic IL-25 and dampens tissue inflammation in patients with recurrent Clostridioides difficile

2021 ◽  
Author(s):  
Ning-Jiun Jan ◽  
Noah Oakland ◽  
Pankaj Kumar ◽  
Girija Ramakrishnan ◽  
Brian W. Behm ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Fecal Microbiota Transplantation ◽  
Alpha Diversity ◽  
The United States ◽  
Fecal Microbiota ◽  
Peripheral Blood Mononuclear ◽  
Clostridioides Difficile ◽  
Rdna Sequencing ◽  
Clostridioides Difficile Infection ◽  
The Impact

Background: Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon. Methods: Subjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT. Results: All 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT. Conclusion: The increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

scholarly journals Heart Failure Is a Risk Factor for Suffering and Dying of Clostridium difficile Infection. Results of a 15-Year Nationwide Study in Spain

2020 ◽  
Vol 9 (3) ◽  
pp. 614
Author(s):  
Manuel Méndez-Bailón ◽  
Rodrigo Jiménez-García ◽  
Valentín Hernández-Barrera ◽  
Javier de Miguel-Díez ◽  
José M. de Miguel-Yanes ◽  
...  
Keyword(s):  
Heart Failure ◽  
Risk Factor ◽  
Time Trends ◽  
Secondary Diagnosis ◽  
National Hospital ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Comorbidity Index ◽  
Index 2 ◽  
Discharge Database

Background: We aimed to (1) analyze time trends in the incidence and in-hospital outcomes of heart failure (HF) patients suffering Clostridioides difficile infection (CDI); (2) compare clinical characteristics of CDI patients between those with HF and matched non-HF patients; and (3) identify predictors of in-hospital mortality (IHM) among HF patients suffering CDI. Methods: Retrospective study using the Spanish National Hospital Discharge Database from 2001 to 2015. Patients of age ≥40 years with CDI were included. For each HF patient, we selected a year, age, sex, and readmission status-matched non-HF patient. Results: We found 44,695 patients hospitalized with CDI (15.46% with HF). HF patients had a higher incidence of CDI (202.05 vs. 145.09 per 100,000 hospitalizations) than patients without HF (adjusted IRR 1.35; 95% CI 1.31–1.40). IHM was significantly higher in patients with HF when CDI was coded as primary (18.39% vs. 7.63%; p < 0.001) and secondary diagnosis (21.12% vs. 14.76%; p < 0.001). Among HF patient’s predictor of IHM were older age (OR 8.80; 95% CI 2.55–20.33 for ≥85 years old), those with more comorbidities (OR 1.68; 95% CI 1.12–2.53 for those with Charlson Comorbidity index ≥2), and in those with severe CDI (OR 6.19; 95% CI 3.80–10.02). Conclusions: This research showed that incidence of CDI was higher in HF than non-HF patients. HF is a risk factor for IHM after suffering CDI.

scholarly journals Clostridioides difficile Infection: A Room for Multifaceted Interventions

2020 ◽  
Vol 9 (12) ◽  
pp. 4114
Author(s):  
Nicola Petrosillo ◽  
Maria Adriana Cataldo
Keyword(s):  
United States ◽  
Health Care ◽  
One Health ◽  
The United States ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Multifaceted Interventions ◽  
Infectious Pathogen

Clostridioides difficile (CD) continues to be the number one health care-associated infectious pathogen in the United States [...]

scholarly journals Risk Factors Associated with Recurrent Clostridioides difficile Infection

Healthcare ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 352
Author(s):  
Nicoleta Negrut ◽  
Simona Bungau ◽  
Tapan Behl ◽  
Shamim Ahmad Khan ◽  
Cosmin Mihai Vesa ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
First Episode ◽  
Old Patients ◽  
Clostridioides Difficile ◽  
Nosocomial Diarrhea ◽  
Clostridioides Difficile Infection ◽  
Comorbidity Index ◽  
Diarrhea Syndrome ◽  
Multiple Episodes

Clostridioides difficile (CD) is responsible for nosocomial diarrhea syndrome with possible severe progression. Recurrence of the disease induces higher health system costs, as well as exposes patients to additional health risks. Patients with recurrence of this disease are difficult to identify, so the purpose of this study is to quantify various demographic, clinical, and treatment factors that could prevent further progression to recurrence of the disease. In the period 2018–2019, about 195 patients were diagnosed with more than one episode of CDI in the three months following the first episode. The recurrence rate for CDI was 53.84% (60.95% for one episode and 39.05% for multiple episodes). Most commonly afflicted were 60–69-year-old patients, or those with higher Charlson Comorbidity Index (CCI). Multiple analyses associated cardiovascular (odds ratios (OR) = 3.02, 95% confidence intervals (CI) = 1.23–7.39, p = 0.015), digestive (OR = 3.58, 95% CI = 1.01–12.63, p = 0.047), dementia (OR = 3.26, 95% CI = 1.26–8.41, p = 0.014), immunosuppressive (OR = 3.88, 95% CI = 1.34–11.21, p = 0.012) comorbidities with recurrences. Risk factor identification in the first episode of CDI could lead to the implementation of treatment strategies to improve the patients’ quality of life affected by this disease.

scholarly journals Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection

2021 ◽  
Vol 14 ◽  
pp. 175628482110481
Author(s):  
Adam Ressler ◽  
Joyce Wang ◽  
Krishna Rao
Keyword(s):  
The United States ◽  
Adverse Outcomes ◽  
Chronic Illnesses ◽  
Narrative Review ◽  
Healthcare Associated Infection ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Patients At Risk ◽  
Hospital Deaths ◽  
Healthcare Associated

In the United States, Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infection, affecting nearly half a million people and resulting in more than 20,000 in-hospital deaths every year. It is therefore imperative to better characterize the intricate interplay between C. difficile microbial factors, host immunologic signatures, and clinical features that are associated with adverse outcomes of severe CDI. In this narrative review, we discuss the implications of C. difficile genetics and virulence factors in the molecular epidemiology of CDI, and the utility of early biomarkers in predicting the clinical trajectory of patients at risk of developing severe CDI. Furthermore, we identify associations between host immune factors and CDI outcomes in both animal models and human studies. Next, we highlight clinical factors including renal dysfunction, aging, blood biomarkers, level of care, and chronic illnesses that can affect severe CDI diagnosis and outcome. Finally, we present our perspectives on two specific treatments pertinent to patient outcomes: metronidazole administration and surgery. Together, this review explores the various venues of CDI research and highlights the importance of integrating microbial, host, and clinical data to help clinicians make optimal treatment decisions based on accurate prediction of disease progression.

scholarly journals Initial vancomycin versus metronidazole for the treatment of first-episode non-severe Clostridioides difficile infection

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Kevin Zhang ◽  
Patricia Beckett ◽  
Salaheddin Abouanaser ◽  
Marek Smieja
Keyword(s):  
Treatment Guidelines ◽  
Multivariable Analysis ◽  
Current Treatment ◽  
Multivariate Logistic Regression Model ◽  
First Episode ◽  
Study Cohort ◽  
Clostridioides Difficile ◽  
Nosocomial Diarrhea ◽  
Clostridioides Difficile Infection ◽  
Incident Infection

Abstract Objective: Clostridioides difficile infection (CDI) is the leading cause of infectious nosocomial diarrhea. Although initial fidaxomicin or vancomycin treatment is recommended by most major guidelines to treat severe CDI, there exists varied recommendations for first-episode non-severe CDI. Given the discrepancy in current treatment guidelines, we sought to evaluate the use of initial vancomycin versus metronidazole for first-episode non-severe CDI. Methods: We conducted a retrospective cohort study of all adult inpatients with first-episode CDI at our institution from January 2013 to May 2018. The initial vancomycin versus initial metronidazole cohorts were examined using a multivariate logistic regression model. Results: The study cohort of 737 patients had a median age of 72.3 years, and 357 of these patients (48.4%) had hospital-acquired infection. Among 326 patients with non-severe CDI, recurrence, new incident infection, and 30-day mortality rates were 16.2%, 10.9%, and 5.3%, respectively, when treated with initial metronidazole, compared to 20.0%, 1.4%, and 10.0%, respectively, when treated with initial vancomycin. In an adjusted multivariable analysis, the use of initial vancomycin for the treatment of non-severe CDI was associated with a reduction in new incident infection (adjusted odds ratio [ORadj], 0.11; 95% confidence interval [CI], 0.02–0.86; P = .035), compared to initial metronidazole. Conclusions: Initial vancomycin was associated with a reduced rate of new incident infection in the treatment of adult inpatients with first-episode non-severe CDI. These findings support the use of initial vancomycin for all inpatients with CDI, when fidaxomicin is unavailable.

scholarly journals Therapeutic Use of Mesenchymal Stromal Cells: The Need for Inclusive Characterization Guidelines to Accommodate All Tissue Sources and Species

2021 ◽  
Vol 9 ◽  
Author(s):  
Adrienne Wright ◽  
Marne L. Arthaud-Day ◽  
Mark L. Weiss
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Standard Of Care ◽  
The United States ◽  
Therapeutic Use ◽  
Therapeutic Modality ◽  
Common Goal ◽  
Immunomodulatory Properties ◽  
Clinical Trial Results

Following their discovery over 50 years ago, mesenchymal stromal cells (MSCs) have become one of the most studied cellular therapeutic products by both academia and industry due to their regenerative potential and immunomodulatory properties. The promise of MSCs as a therapeutic modality has been demonstrated by preclinical data yet has not translated to consistent, successful clinical trial results in humans. Despite the disparities across the field, MSC shareholders are unified under one common goal—to use MSCs as a therapeutic modality to improve the quality of life for those suffering from a malady in which the standard of care is suboptimal or no longer effective. Currently, there is no Food and Drug Administration (FDA)-approved MSC therapy on the market in the United States although several MSC products have been granted regulatory approval in other countries. In this review, we intend to identify hurdles that are impeding therapeutic progress and discuss strategies that may aid in accomplishing this universal goal of widespread therapeutic use.

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