Epidemiologia da Infeção por Clostridioides Difficile em Portugal: um Estudo Retrospetivo, Observacional em Doentes Hospitalizados

Introduction: Clostridioides difficile is the main cause of healthcare-associated diarrhea in Europe and North America. The aim of this study was to characterize the epidemiology and clinical burden of Clostridioides difficile infection among hospitalized patients in Portugal. Material and methods: Retrospective study conducted in six public hospital centers in Portugal. All primary Clostridioides difficile infection episodes and related recurrences occurring in 2017, as well as episodes developing two to eight weeks after the last episode diagnosed in that year, were documented. The National Reference Laboratory (National Institute of Health Dr. Ricardo Jorge) provided national surveillance data on Clostridioides difficile infection. Results: A total of 385 inpatients with at least one primary episode diagnosed in 2017 were included. Most patients were aged over 70 years-old (73.2%). The included patients developed 451 episodes during the observation period. Approximately 44% of primary episodes were community-associated. Most episodes (94.9%) occurred in patients with one or more risk factors, with recent antibiotic exposure being particularly common (86.0%). All-cause in-hospital mortality was 19.5%, being significantly higher in patients aged over 65 years-old versus those aged 18 to 64 years-old (22.4% vs 7.8%, respectively). Over 50 different ribotypes were observed among 206 Clostridioides difficile strains received by the National Reference Laboratory. Conclusion: In Portugal, hospitalized patients with Clostridioides difficile infection are mostly older patients presenting risk factors for the development of this infection, particularly recent antibiotic exposure. Mortality is disproportionately high among the older population. Community-associated Clostridioides difficile infection is common among inpatients with this infection.info:eu-repo/semantics/publishedVersio

Trends In Recurrent Clostridioides Difficile Infection In New Haven County

Background: Recurrent Clostridioides difficile infection (CDI) is a cause of increased burden on the healthcare system and factors associated with this disease merit understanding. This study aimed to determine the incidence rate and to describe the factors associated with recurrent CDI cases in New Haven County from 2015 to 2020. It also examined the trends in annual recurrent CDI cases across epidemiological classes. Methods: This study utilized data from a population-based surveillance program of the Healthcare-Associated Infectious Community Interface (HAIC) Program within the Connecticut Emerging Infectious Program (CT EIP) at Yale School of Public Health which served all residents of New Haven County. Annual incidence rates of CDI and recurrent CDI in aggregate and by epidemiological class were calculated. Logistic regression analysis was carried out to determine factors associated with recurrent CDI. Results: Among 7,023 CDI cases from 2015-2020, the incidence rate of CDI in 2015 and 2020 was 165.2 and 107.8 per 100,000 persons respectively (median=140.2/100,000 persons; IQR=25.6/100,000 persons). Overall, 12% of 4,301 CDI cases with complete chart reviews had recurrent CDI, which made up 13.6% of all HCFO-CDI, 14.1% of all CO-HCFA CDI, and 10.5% of all CA-CDI. Specifically, 18.1 and 16.9 per 100 persons in 2015 and 2020 respectively had recurrent CDI (median=11.3/100 persons; IQR=4.7/100 persons). There were a 37.3% and 2.3% increase in recurrent CDI among HCFO and CA cases respectively from 2019 to 2020. A significant proportion of those who had recurrent CDI were older (median age=70.0 years, IQR=23.0 years; median age of non-recurrent group=64.0 years, IQR=26.0 years, p\u3c0.001), female (recurrent of 66.0% vs non-recurrent of 61.3% p\u3c0.039), White race, non-Hispanic, and had healthcare-associated incident CDI. In the final multivariable model, there was a higher risk of recurrent CDI among individuals who had malignancies (OR, 1.51; 95% CI, 1.11-2.07), used nitrofurantoin (OR, 2.37; 95% CI, 1.23-4.58), or were of White race. Also, cases with incident CDI in 2017 (OR, 0.43; 95% CI, 0.26-0.73), 2018 (OR, 0.60; 95% CI, 0.37-0.97), and 2019 (OR, 0.50; 95% CI, 0.30-0.84) had lower risk of recurrent CDI when compared with incident CDI cases in 2015. Conclusions: There was a lowered risk of recurrent CDI over time (from 2015-2019) which may reflect effective measures in management of CDI. The loss of this pattern in 2020 with an increase in HCFO recurrent cases may reflect the impact of the COVID-19 pandemic in 2020. Older persons, White individuals, and those with malignancies are particularly vulnerable to recurrent CDI. Keywords: Chronic Disease Epidemiology, Thesis, Clostridioides difficile, CDI, recurrent CDI, recurrent Clostridioides difficil

SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Clostridioides difficile Infection (rCDI)

Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20–25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance. Current FDA-approved CDI treatment strategies target toxin or toxin-producing bacteria, but do not address microbiome disruption, which is key to the pathogenesis of recurrent CDI. Fecal microbiota transplantation (FMT) reduces the risk of recurrent CDI through the restoration of microbial diversity. However, FDA safety alerts describing hospitalizations and deaths related to pathogen transmission have raised safety concerns with the use of unregulated and unstandardized donor-derived products. SER-109 is an investigational oral microbiome therapeutic composed of purified spore-forming Firmicutes. SER-109 was superior to a placebo in reducing CDI recurrence at Week 8 (12% vs. 40%, respectively; p \u3c 0.001) in adults with a history of recurrent CDI with a favorable observed safety profile. Here, we discuss the role of the microbiome in CDI pathogenesis and the clinical development of SER-109, including its rigorous manufacturing process, which mitigates the risk of pathogen transmission. Additionally, we discuss compositional and functional changes in the gastrointestinal microbiome in patients with recurrent CDI following treatment with SER-109 that are critical to a sustained clinical response

Influence of Antibiotic Exposure Intensity on the Risk of Clostridioides Difficile Infection

Antibiotics are a strong risk factor for Clostridioides difficile infection (CDI), and CDI incidence is often measured as an important outcome metric for antimicrobial stewardship interventions aiming to reduce antibiotic use. However, risk of CDI from antibiotics varies by agent and dependent on the intensity (i.e., spectrum and duration) of antibiotic therapy. Thus, the impact of stewardship interventions on CDI incidence is variable, and understanding this risk requires a more granular measure of intensity of therapy than traditionally used measures like days of therapy (DOT)

A retrospective assessment of guideline adherence and treatment outcomes from Clostridioides difficile infection following the IDSA 2021 clinical guideline update: Clostridioides difficile infection

BACKGROUND: The 2021 update to the Infectious Diseases Society of America METHODS: This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections. RESULTS: A total of 45 049 patients with CDI from 779 US hospitals met initial inclusion criteria. Comparing the pre vs post periods, the proportion of patients treated with fidaxomicin increased from 5.9% to 13.7% ( CONCLUSIONS: Since the 2021 guideline update, fidaxomicin use has increased significantly but could be further utilized given its association with better clinical outcomes and no increase in postdischarge costs

Concurrent and Subsequent Co-Infections of Clostridioides difficile Colitis in the Era of Gut Microbiota and Expanding Treatment Options

We narratively reviewed the physiopathology, epidemiology, and management of co-infections in Clostridioides difficile colitis (CDI) by searching the following keywords in Embase, MedLine, and PubMed: “Clostridium/Clostridioides difficile”, “co-infection”, “blood-stream infection” (BSI), “fungemia”, “Candida”, “Cytomegalovirus”, “probiotics”, “microbial translocation” (MT). Bacterial BSIs (mainly by Enterobacteriaceae and Enterococcus) and fungemia (mainly by Candida albicans) may occur in up to 20% and 9% of CDI, increasing mortality and length of hospitalization. Up to 68% of the isolates are multi-drug-resistant bacteria. A pivotal role is played by gut dysbiosis, intestinal barrier leakage, and MT. Specific risk factors are represented by CDI-inducing broad-spectrum antibiotics, oral vancomycin use, and CDI severity. Probiotics administration (mainly Saccharomyces and Lactobacillus) during moderate/severe CDI may favor probiotics superinfection. Other co-infections (such as Cytomegalovirus or protozoa) can complicate limited and specific cases. There is mounting evidence that fidaxomicin, bezlotoxumab, and fecal microbiota transplantation can significantly reduce the rate of co-infections compared to historical therapies by interrupting the vicious circle between CDI, treatments, and MT. Bacterial BSIs and candidemia represent the most common co-infections in CDI. Physicians should be aware of this complication to promptly diagnose and treat it and enforce preventive strategies that include a more comprehensive consideration of newer treatment options

Economic burden of recurrent Clostridioides difficile infection in adults admitted to Spanish hospitals. A multicentre retrospective observational study

Objective: Clostridioides difficile infection (CDI) is associated with increased hospital stays and mortality and a high likelihood of rehospitalization, leading to increased health resource use and costs. The objective was to estimate the economic burden of recurrent CDI (rCDI). Methods: observational, retrospective study carried out in six hospitals. Adults aged ≥18 years with ≥1 confirmed diagnosis (primary or secondary) of rCDI between January 2010 and May 2018 were included. rCDI-related resource use included days of hospital stay (emergency room, ward, isolation and ICU), tests and treatments. For patients with primary diagnosis of rCDI, the complete hospital stay was attributed to rCDI. When diagnosis of rCDI was secondary, hospital stay attributed to rCDI was estimated using 1:1 propensity score matching as the difference in hospital stay compared to controls. Controls were hospitalizations without CDI recorded in the Spanish National Hospital Discharge Database. The cost was calculated by multiplying the natural resource units by the unit cost. Costs (euros) were updated to 2019. Results: we included 282 rCDI episodes (188 as primary diagnosis): 66.31% of patients were aged ≥65 years and 57.80% were female. The mean hospital stay (SD) was 17.18 (23.27) days: 86.17% of rCDI episodes were isolated for a mean (SD) of 10.30 (9.97) days. The total mean cost (95%-CI) per episode was 10,877 (9,499-12,777), of which the hospital stay accounted for 92.56. Conclusions: there is high cost and resource use associated with rCDI, highlighting the importance of preventing rCDI to the Spanish National Health System

Economic impact of recurrent Clostridioides difficile infection in the USA: A systematic literature review and cost synthesis

INTRODUCTION: Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America. METHODS: English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer\u27s perspective. RESULTS: A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to$82,268. CONCLUSIONS: While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers

Estimating excess mortality and economic burden of <i>Clostridioides difficile</i> infections and recurrences during 2015–2019:The RECUR England study

Objective To generate real-world evidence on all-cause mortality and economic burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. Methods We conducted a cohort study using retrospective data from Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients diagnosed with CDI in hospital and community settings during 2015–2018 were included and followed for ≥1year. All-cause mortality was described at 6-, 12-, and 24-months. Healthcare resource usage (HCRU) and associated costs were assessed at 12-months of follow-up. A cohort of non-CDI patients, matched by demographic and clinical characteristics including Charlson Comorbidity Index score, was used to assess excess mortality and incremental costs of HCRU. Results All-cause mortality among CDI patients at 6-, 12-, and 24-months was 15.87%, 20.37%, and 27.03%, respectively. A higher proportion of rCDI patients died at any point during follow-up. Compared with matched non-CDI patients, excess mortality was highest at 6-months with 1.81 and 2.53 deaths per 100 patient-months among CDI and ≥1 rCDI patients. Hospitalisations were the main drivers of costs, with an incremental cost of £1,209.21 per CDI patient. HCRU and costs increased with rCDIs. Conclusions CDI poses a substantial mortality and economic burden, further amplified by rCDIs