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 Risk for Clostridioides difficile infection among hospitalized patients associated with multiple healthcare exposures prior to admission

2020 ◽  
Author(s):  
Aaron C Miller ◽  
Daniel K Sewell ◽  
Alberto M Segre ◽  
Sriram V Pemmaraju ◽  
Philip M Polgreen ◽  
...  
Keyword(s):  
Hospitalized Patients ◽  
Healthcare Associated Infection ◽  
Case Definitions ◽  
Multiple Exposures ◽  
Clostridioides Difficile ◽  
Increased Risk ◽  
Increase Risk ◽  
Clostridioides Difficile Infection ◽  
Degree Of Association ◽  
Healthcare Associated

Abstract Purpose Clostridioides difficile infections (CDIs) are a common healthcare-associated infection and often used as indicators of hospital safety or quality. However, healthcare exposures occurring prior to hospitalization may increase risk for CDI. We conduct a case-control study comparing hospitalized patients with and without CDI to determine if healthcare exposures prior to hospitalization (i.e., clinic visits, antibiotics, family members with CDI) were associated with increased risk for hospital onset CDI, and how risk varied with time between exposure and hospitalization. Methods Records were collected from a large insurance-claims database from 2001-2017 for hospitalized adult patients. Prior healthcare exposures were identified using inpatient, outpatient, emergency department, and prescription drug claims; results were compared between various CDI case definitions. Results Hospitalized patients with CDI had significantly more frequent healthcare exposures prior to admission. Healthcare visits, antibiotics and family exposures were associated with greater likelihood of CDI during hospitalization. The degree of association diminished with time between exposure and hospitalization. Results were consistent across CDI case definitions. Conclusions Many different prior healthcare exposures appear to increase risk for CDI presenting during hospitalization. Moreover, patients with CDI typically have multiple exposures prior to admission, confounding the ability to attribute cases to a particular stay.

scholarly journals 2404. Molecular Epidemiology of Clostridioides difficile in the United States, 2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S830-S830 ◽  
Author(s):  
Ashley Paulick ◽  
Michelle Adamczyk ◽  
Lauren C Korhonen ◽  
Alice Guh ◽  
Amy Gargis ◽  
...  
Keyword(s):  
United States ◽  
Molecular Epidemiology ◽  
The United States ◽  
Emerging Infections ◽  
Convenience Sample ◽  
Clostridioides Difficile ◽  
Positive Stool ◽  
Control And Prevention ◽  
Clostridioides Difficile Infection ◽  
Healthcare Associated

Abstract Background In 2009, the Centers for Disease Control and Prevention (CDC) implemented Clostridioides difficile infection (CDI) surveillance through the Emerging Infections Program (EIP) to monitor the incidence and evolving epidemiology of CDI in the United States. Since 2012, ribotypes (RTs) 027, 106, 002, 014, and 020 have constituted the top five strain types among both US community- and healthcare-associated isolates. Here we describe the changes in molecular epidemiology of C. difficile isolates collected in the United States in 2017. Methods In 2017, CDI surveillance was conducted at 10 EIP sites (CA, CO, CT, GA, MD, MN, NM, NY, OR, and TN). A convenience sample of clinical laboratories across EIP sites submitted C. difficile-positive stool specimens to the MN Department of Health Public Health Laboratory and Hines VA Hospital (IL) for culture. Isolates were forwarded to CDC and characterized by capillary-based PCR-ribotyping and PCR detection of tcdA, tcdB, cdtA, cdtB, and deletions in tcdC. Results In 2017, 1,051 C. difficile isolates were submitted; the total number of isolates received from each site ranged from 11 to 286 with a median of 85.5. In total, 143 RTs were observed, with the majority of isolates harboring toxin genes tcdA and tcdB (95%) and a wild-type tcdC sequence (71%). Among 556 healthcare-associated isolates, RT 027 was the most prevalent and the top RT at 5 sites (CA, GA, MD, NM, TN). Ribotype 106 was the most prevalent among 495 community-associated CA isolates and the top RT at 6 sites (CO, CT, GA, MD, MN, TN). Ribotype 027 significantly decreased from 2012 to 2017 among both healthcare-associated (21% vs 15%; p = 0.02) and community-associated isolates (17% vs 6%; P < 0.0001). Among healthcare-associated isolates, RT 076, which was observed in 8 EIP sites, increased from 2% in 2016 to 5% in 2017 (p = 0.05) and replaced RT 020 as one of the top 5 healthcare-associated RTs in 2017. Conclusion Despite an overall decline since 2012, RT 027 remained the most prevalent RT among healthcare-associated isolates submitted in 2017. The increased frequency of RT 076 among healthcare-associated isolates submitted in 2017 highlights the evolving molecular epidemiology of C. difficile and the need for continued surveillance to monitor potential emerging strains. Disclosures All authors: No reported disclosures.

scholarly journals 1016. Standardized Antimicrobial Administration Ratio (SAAR) and Clostridioides difficile Infection Standardized Infection Ratio (SIR): Are they connected? An Evaluation of 28 Hospitals

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S357-S357
Author(s):  
Danielle Sebastian ◽  
Florian Daragjati ◽  
Karl Saake ◽  
Lisa K Sturm ◽  
Mohamad G Fakih
Keyword(s):  
Antimicrobial Agent ◽  
Broad Spectrum ◽  
Antibacterial Agents ◽  
Control Strategies ◽  
Antibiotic Use ◽  
Healthcare Associated Infection ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Healthcare Associated ◽  
Antimicrobial Administration

Abstract Background Clostridioides difficile infections (CDIs) are the most prevalent healthcare-associated infection in the U.S. Of all CDIs, most are related to healthcare exposures and are potentially preventable by reducing unnecessary antibiotic use and interrupting patient-to-patient transmission of CDI. Methods The adult SAARs for 4 antimicrobial agent categories were compared with the CDI SIR at 28 facilities with greater than 100 beds across the health system for the calendar year of 2018. The 4 adult antimicrobial agent categories chosen for comparison were: antibacterial agents posing the highest risk for CDI, broad-spectrum antibacterial agents predominantly used for hospital-onset infections (BSHO), broad-spectrum antibacterial agents predominantly used for community-acquired infections (BSCA) and all antibacterial agents. Results The 2018 aggregate CDI SIR for the 28 facilities was 0.609. The aggregate SAAR for the adult antimicrobial agent categories were 1.05 for the antibacterial agents posing the highest risk for CDI, 1.05 for BSHO, 0.88 for BSCA, and 1.03 for all antibacterial agents. No correlation was seen between any of the 4 adult SAAR antimicrobial agent categories and the facility CDI SIR (Figure 1–4). Conclusion While reducing unnecessary antibiotics is an important strategy in preventing CDIs, having a higher observed vs. predicted administration ratio in the four antimicrobial agent categories studied was not correlated with a higher CDI SIR, including the CDI SAAR category. Reduction of CDI is challenging requiring a multipronged approach to include infection control strategies, appropriate testing, and antimicrobial stewardship. Disclosures All authors: No reported disclosures.

scholarly journals Epidemiology of community-acquired and recurrent Clostridioides difficile infection

2021 ◽  
Vol 14 ◽  
pp. 175628482110162
Author(s):  
Yichun Fu ◽  
Yuying Luo ◽  
Ari M Grinspan
Keyword(s):  
Large Scale ◽  
Infection Prevention ◽  
The United States ◽  
Future Research ◽  
Clostridioides Difficile ◽  
Epidemiologic Surveillance ◽  
Scale Population ◽  
Clostridioides Difficile Infection ◽  
Healthcare Associated ◽  
Hospital Acquired

Clostridioides difficile infection is a leading cause of healthcare-associated infections with significant morbidity and mortality. For the past decade, the bulk of infection prevention and epidemiologic surveillance efforts have been directed toward mitigating hospital-acquired C. difficile. However, the incidence of community-associated infection is on the rise. Patients with community-associated C. difficile tend to be younger and have lower mortality rate. Rates of recurrent C. difficile infection overall have decreased in the United States, but future research and public health endeavors are needed to standardize and improve disease detection, stratify risk factors in large-scale population studies, and to identify regional and local variations in strain types, reservoirs and transmission routes to help characterize and combat the changing epidemiology of C. difficile.

scholarly journals Recent advances in the treatment of Clostridioides difficile infection: the ever-changing guidelines

2020 ◽  
Vol 9 ◽  
Author(s):  
Shruti Khurana ◽  
Alyssa Kahl ◽  
Kevin Yu ◽  
Andrew W DuPont
Keyword(s):  
Infectious Diseases ◽  
Diagnostic Testing ◽  
Antibody Therapy ◽  
Treatment Strategies ◽  
Current Evidence ◽  
Healthcare Associated Infection ◽  
The Past ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Healthcare Associated

Clostridioides difficile infection (CDI), formerly known as Clostridium difficile, continues to be the most common healthcare-associated infection worldwide. With the shifting epidemiology towards higher a incidence of community-acquired CDI and the continued burden on the healthcare system posed by high rates of CDI recurrence, there has been an impetus to advance the diagnostic testing and treatment strategies. Recent advancements over the past decade have led to rapidly changing guidelines issued by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases. With our comprehensive review, we aim to summarize the latest advances in diagnosing and treating CDI and thus attempt to help readers guide best practices for patient care. This article also focusses on cost-effectiveness of various therapies currently available on the market and provides an analysis of the current evidence on a relatively new monoclonal antibody therapy, Bezlotoxumab, to treat recurrent CDI.

scholarly journals Systemic Inflammatory Mediators Are Effective Biomarkers for Predicting Adverse Outcomes in Clostridioides difficile Infection

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Michael G. Dieterle ◽  
Rosemary Putler ◽  
D. Alexander Perry ◽  
Anitha Menon ◽  
Lisa Abernathy-Close ◽  
...  
Keyword(s):  
Severe Disease ◽  
The United States ◽  
Human Infection ◽  
Serum Biomarkers ◽  
Adverse Outcomes ◽  
Gastrointestinal Infections ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Increased Risk ◽  
Patients At Risk

ABSTRACT Clostridioides difficile infection (CDI) can result in severe disease and death, with no accurate models that allow for early prediction of adverse outcomes. To address this need, we sought to develop serum-based biomarker models to predict CDI outcomes. We prospectively collected sera ≤48 h after diagnosis of CDI in two cohorts. Biomarkers were measured with a custom multiplex bead array assay. Patients were classified using IDSA severity criteria and the development of disease-related complications (DRCs), which were defined as ICU admission, colectomy, and/or death attributed to CDI. Unadjusted and adjusted models were built using logistic and elastic net modeling. The best model for severity included procalcitonin (PCT) and hepatocyte growth factor (HGF) with an area (AUC) under the receiver operating characteristic (ROC) curve of 0.74 (95% confidence interval, 0.67 to 0.81). The best model for 30-day mortality included interleukin-8 (IL-8), PCT, CXCL-5, IP-10, and IL-2Rα with an AUC of 0.89 (0.84 to 0.95). The best model for DRCs included IL-8, procalcitonin, HGF, and IL-2Rα with an AUC of 0.84 (0.73 to 0.94). To validate our models, we employed experimental infection of mice with C. difficile. Antibiotic-treated mice were challenged with C. difficile and a similar panel of serum biomarkers was measured. Applying each model to the mouse cohort of severe and nonsevere CDI revealed AUCs of 0.59 (0.44 to 0.74), 0.96 (0.90 to 1.0), and 0.89 (0.81 to 0.97). In both human and murine CDI, models based on serum biomarkers predicted adverse CDI outcomes. Our results support the use of serum-based biomarker panels to inform Clostridioides difficile infection treatment. IMPORTANCE Each year in the United States, Clostridioides difficile causes nearly 500,000 gastrointestinal infections that range from mild diarrhea to severe colitis and death. The ability to identify patients at increased risk for severe disease or mortality at the time of diagnosis of C. difficile infection (CDI) would allow clinicians to effectively allocate disease modifying therapies. In this study, we developed models consisting of only a small number of serum biomarkers that are capable of predicting both 30-day all-cause mortality and adverse outcomes of patients at time of CDI diagnosis. We were able to validate these models through experimental mouse infection. This provides evidence that the biomarkers reflect the underlying pathophysiology and that our mouse model of CDI reflects the pathogenesis of human infection. Predictive models can not only assist clinicians in identifying patients at risk for severe CDI but also be utilized for targeted enrollment in clinical trials aimed at reduction of adverse outcomes from severe CDI.

scholarly journals Phylogenomic analysis of Clostridioides difficile ribotype 106 strains reveals novel genetic islands and emergent phenotypes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bryan Angelo P. Roxas ◽  
Jennifer Lising Roxas ◽  
Rachel Claus-Walker ◽  
Anusha Harishankar ◽  
Asad Mansoor ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Diarrheal Disease ◽  
The United States ◽  
Genomic Islands ◽  
Rapid Expansion ◽  
Phylogenomic Analysis ◽  
Community Settings ◽  
Hamster Model ◽  
Clostridioides Difficile ◽  
Healthcare Associated

AbstractClostridioides difficile infection (CDI) is a major healthcare-associated diarrheal disease. Consistent with trends across the United States, C. difficile RT106 was the second-most prevalent molecular type in our surveillance in Arizona from 2015 to 2018. A representative RT106 strain displayed robust virulence and 100% lethality in the hamster model of acute CDI. We identified a unique 46 KB genomic island (GI1) in all RT106 strains sequenced to date, including those in public databases. GI1 was not found in its entirety in any other C. difficile clade, or indeed, in any other microbial genome; however, smaller segments were detected in Enterococcus faecium strains. Molecular clock analyses suggested that GI1 was horizontally acquired and sequentially assembled over time. GI1 encodes homologs of VanZ and a SrtB-anchored collagen-binding adhesin, and correspondingly, all tested RT106 strains had increased teicoplanin resistance, and a majority displayed collagen-dependent biofilm formation. Two additional genomic islands (GI2 and GI3) were also present in a subset of RT106 strains. All three islands are predicted to encode mobile genetic elements as well as virulence factors. Emergent phenotypes associated with these genetic islands may have contributed to the relatively rapid expansion of RT106 in US healthcare and community settings.

scholarly journals The interplay of Clostridioides difficile infection and inflammatory bowel disease

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.

scholarly journals Shifting Landscape of Healthcare-Associated Infection and Antimicrobial Resistant Infection Reporting Policy, 2005–2019

2020 ◽  
Vol 41 (S1) ◽  
pp. s389-s389
Author(s):  
Jeremy Goodman ◽  
Samuel Clasp ◽  
Arjun Srinivasan ◽  
Elizabeth Mothershed ◽  
Seth Kroop ◽  
...  
Keyword(s):  
Health Department ◽  
Adverse Outcomes ◽  
Health Departments ◽  
Healthcare Associated Infection ◽  
Candida Auris ◽  
Quality Reporting ◽  
Notifiable Diseases ◽  
Reporting Requirements ◽  
Resistant Infection ◽  
Healthcare Associated

Background: Healthcare-associated infections (HAIs) are a serious threat to patient safety; they account for substantial morbidity, mortality, and healthcare costs. Healthcare practices, such as inappropriate use of antimicrobials, can also amplify the problem of antimicrobial resistance. Data collected to target HAI prevention and antimicrobial stewardship efforts and measure progress are an important resource for assuring transparency and accountability in healthcare, tracking adverse outcomes, investigating healthcare practices that may spread or protect against disease, detecting and responding to the spread of resistant pathogens, preventing infections, and saving lives. Methods: We discuss 3 healthcare-associated infection and antimicrobial Resistant infection (HAI-AR) reporting types: NHSN HAI-AR reporting, reportable diseases, and nationally notifiable diseases. HAI-AR reporting requirements outline facilities and data to report to NHSN and the health department to comply with state laws. Reportable diseases are those that facilities, providers, and laboratories are required to report to the health department. Nationally notifiable diseases are those reported by health departments to the CDC for nationwide surveillance and analysis as determined by Council of State and Territorial Epidemiologists (CSTE) and the CDC. Data presented are based on state and federal policy; NHSN data are based on CDC reporting statistics. Results: Since the 2005 launch of the CDC NHSN and publication of federal advisory committee HAI reporting guidance, most states have established policies stipulating healthcare facilities in their jurisdiction report HAIs and resistant infections to the NHSN to gain access to those data, increasing from 2 states in 2005, to 18 in 2010, and to 36 states, Washington, DC, and Philadelphia in 2019. Reporting policies and NHSN participation expanded greatly following the 2011 inception of CMS HAI quality reporting requirements, with several states aligning state requirements with CMS reporting. States listing carbapenem-resistant Enterobacteriaceae (CRE) as a reportable disease increased from 7 in 2013 to 41 states and the District of Columbia in 2019. Vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus (VISA/VRSA) was added as a nationally notifiable disease in 2004, carbapenemase-producing CRE (CP-CRE) was added in 2018, and Candida auris clinical infections were added in 2019. The CDC and most jurisdictions with HAI reporting mandates issue public reports based on aggregate state data and/or facility-level data. States may also alert healthcare providers and health departments of emerging threats and to assist in notifying patients of potential exposure. Conclusions: Through efforts by health departments, facilities, patient advocates, partners, the CDC, and other federal agencies, HAI-AR reporting has steadily increased. Although reporting laws and data uses vary between jurisdictions, data provided serves as valuable tools to inform prevention.Funding: NoneDisclosures: None

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