What’s metal got to do with it? Transition metals in Clostridioides difficile infection

Abstract Background There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI. Methods Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure. Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System Conclusion Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI. Disclosures All Authors: No reported disclosures

Download Full-text

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

Journal of Clinical Medicine ◽

10.3390/jcm10010002 ◽

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.

Download Full-text

Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis

SAGE Open Medicine ◽

10.1177/2050312120986733 ◽

2021 ◽

Vol 9 ◽

pp. 205031212098673

Author(s):

Paul Feuerstadt ◽

Mena Boules ◽

Laura Stong ◽

David N Dahdal ◽

Naomi C Sacks ◽

...

Keyword(s):

Loop Ileostomy ◽

Charlson Comorbidity Index Score ◽

Real World Data ◽

Infection Group ◽

Bowel Surgery ◽

Clinical Complications ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Infection Episode

Objective: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. Methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18–64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). Results: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. Conclusions: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

Download Full-text

Analysis of National Healthcare Safety Network Clostridioides difficile Infection Standardized Infection Ratio by Test Type

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.624 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s116-s118

Author(s):

Qunna Li ◽

Andrea Benin ◽

Alice Guh ◽

Margaret A. Dudeck ◽

Katherine Allen-Bridson ◽

...

Keyword(s):

Risk Adjustment ◽

Healthcare Facility ◽

Directional Pattern ◽

Incidence Rates ◽

Nucleic Acid Amplification ◽

Test Type ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

The Mean ◽

The Difference

Background: The NHSN has used positive laboratory tests for surveillance of Clostridioides difficile infection (CDI) LabID events since 2009. Typically, CDIs are detected using enzyme immunoassays (EIAs), nucleic acid amplification tests (NAATs), or various test combinations. The NHSN uses a risk-adjusted, standardized infection ratio (SIR) to assess healthcare facility-onset (HO) CDI. Despite including test type in the risk adjustment, some hospital personnel and other stakeholders are concerned that NAAT use is associated with higher SIRs than are EIAs. To investigate this issue, we analyzed NHSN data from acute-care hospitals for July 1, 2017 through June 30, 2018. Methods: Calendar quarters for which CDI test type was reported as NAAT (includes NAAT, glutamate dehydrogenase (GDH)+NAAT and GDH+EIA followed by NAAT if discrepant) or EIA (includes EIA and GDH+EIA) were selected. HO CDI SIRs were calculated for facility-wide inpatient locations. We conducted the following analyses: (1) Among hospitals that did not switch their test type, we compared the distribution of HO incident rates and SIRs by those reporting NAAT vs EIA. (2) Among hospitals that switched their test type, we selected quarters with a stable switch pattern of 2 consecutive quarters of each of EIA and NAAT (categorized as pattern EIA-to-NAAT or NAAT-to-EIA). Pooled semiannual SIRs for EIA and NAAT were calculated, and a paired t test was used to evaluate the difference of SIRs by switch pattern. Results: Most hospitals did not switch test types (3,242, 89%), and 2,872 (89%) reported sufficient data to calculate SIRs, with 2,444 (85%) using NAAT. The crude pooled HO CDI incidence rates for hospitals using EIA clustered at the lower end of the histogram versus rates for NAAT (Fig. 1). The SIR distributions of both NAAT and EIA overlapped substantially and covered a similar range of SIR values (Fig. 1). Among hospitals with a switch pattern, hospitals were equally likely to have an increase or decrease in their SIR (Fig. 2). The mean SIR difference for the 42 hospitals switching from EIA to NAAT was 0.048 (95% CI, −0.189 to 0.284; P = .688). The mean SIR difference for the 26 hospitals switching from NAAT to EIA was 0.162 (95% CI, −0.048 to 0.371; P = .124). Conclusions: The pattern of SIR distributions of both NAAT and EIA substantiate the soundness of NHSN risk adjustment for CDI test types. Switching test type did not produce a consistent directional pattern in SIR that was statistically significant.Disclosures: NoneFunding: None

Download Full-text

The interplay of Clostridioides difficile infection and inflammatory bowel disease

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211020285 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110202

Author(s):

Kanika Sehgal ◽

Devvrat Yadav ◽

Sahil Khanna

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Adverse Outcomes ◽

Molecular Tests ◽

Clostridioides Difficile ◽

Increased Risk ◽

Clostridioides Difficile Infection ◽

Pros And Cons ◽

Inflammatory Bowel ◽

High Index Of Suspicion

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.

Download Full-text