Search

Background: The increasing incidence of antibiotic-associated diarrhoea (AAD) is a serious health care problem. Dysbiosis of the gut microbiota is suspected to play a role in the pathogenesis of AAD, but its impact on the clinical outcomes of patients remains unclear., Methods: Between May and October 2022, 210 patients with AAD admitted to a university hospital and 100 healthy controls were recruited. DNA extraction from stool specimens and shotgun sequencing were performed. Machine learning was conducted to assess profiling at different taxonomic levels and to select variables for multivariable analyses., Results: Patients were classified into two groups: Clostridioides difficile infection (CDI, n = 39) and non-CDI AAD (n = 171). The in-hospital mortality rate for the patients was 20.0%, but the presence of C. difficile in the gut microbiota was not associated with mortality. Machine learning showed that taxonomic profiling at the genus level best reflected patient prognosis. The in-hospital mortality of patients was associated with the relative abundance of specific gut microbial genera rather than alpha-diversity: each of the five genera correlated either positively (Enterococcus, Klebsiella, Corynebacterium, Pseudomonas, and Anaerofustis) or negatively (Bifidobacterium, Bacteroides, Streptococcus, Faecalibacterium, and Dorea). Genes for vancomycin resistance were significantly associated with in-hospital mortality in patients with AAD (adjusted hazard ratios, 2.45; 95% CI, 1.20-4.99)., Conclusion: This study demonstrates the potential utility of metagenomic studies of the gut microbial community as a biomarker for prognosis prediction in AAD patients., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study., Methods: The IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections., Results: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33-0.65]; non-severe: HR 0.39; [95% CI, 0.24-0.60]; severe: HR 0.52; [95% CI, 0.28-0.95])., Discussion: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Japanese guidelines recommend metronidazole (MNZ) and vancomycin (VCM) for non-severe and severe cases of Clostridioides difficile infection (CDI), respectively. In the present study, we investigated the use of CDI antimicrobials and evaluated their clinical efficacy and validity using four severity classifications. A retrospective chart review was conducted using the data of 137 inpatients with initially positive C. difficile toxin test results and the initiation of CDI antimicrobials between April 2015 and March 2019. Patients treated with VCM or oral MNZ were included for clinical efficacy analysis of CDI antimicrobials and validation of severity classifications. The endpoints were CDI recurrence, 30-day mortality, and diarrhea cure rates. No significant differences were found between the VCM and oral MNZ groups in the CDI recurrence rate (10.4% vs. 12.7%, P = 0.707), 30-day mortality rate (12.5% vs. 5.6%, P = 0.162), and diarrhea cure rate (61.9% vs. 72.7%, P = 0.238), regardless of severity. Treatment with oral MNZ for non-severe cases was promising, confirming its usefulness according to Japanese guidelines. Further investigation of the clinical efficacy of oral MNZ in patients with first-episode CDI and evaluation of the preferred severity classification are warranted.

Background: To estimate the global trends and disease burden of Clostridioides difficile infection (CDI) and its correlation with worldwide antibiotic consumption., Methods: Clostridioides difficile infection and antibiotic consumption data were retrieved from the Global Burden of Disease 2019, ResistanceMap-AntibiocUse, Food and Drug Administration (FDA) Adverse Event Reporting System, and Global Antimicrobial Resistance and Use Surveillance System. Jointpoint regression and age-period-cohort model were developed to show the global trends and burden of CDI. Correlation tests were calculated to explore the relationship between CDI and antibiotics., Results: Globally, CDI is the most significant one with a high-rocketing burden increase rate among 13 pathogens causing diarrheal deaths and disability-adjusted life years (DALYs). The age-standardised death rate (ASDR) increased from 0.19 in 1990 to 0.43 in 2019, in which the elderly and females are at higher risk. A rapid increase in ASDR in high to middle sociodemographic index (SDI) regions such as North America (average annual percentage change (AAPC) = 7.71%), Andean (AAPC = 7.82%), and Southern Latin America (AAPC = 11.08%) was identified. Antibiotic consumption has a significant positive correlation with CDI with different risk stratifications., Conclusions: The global burden of CDI has continuously increased for the past 30 years, especially in high to middle-SDI regions. World antibiotic consumption showed a strong positive correlation with CDI with different risk stratification. More effective prevention and control measures should be implemented in these critical regions, with a specific emphasis on vulnerable populations, to mitigate the spread of epidemics., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Purpose: To compare the efficacy, recurrence rate, adverse event rate and mortality of fidaxomicin compared with vancomycin in treating different types of Clostridium difficile infection (CDI)., Methods: A systematic search was conducted on PubMed, Embase, Web of Science, Cochrane Library and clinical trial registration databases for research on fidaxomicin versus vancomycin in the treatment of CDI and the retrieval period extended from the establishment of the database to July 22, 2022. A total of 15 studies were included, including 8 RCTs and 7 retrospective cohort studies., Results: Results showed that there was no significant difference in the overall efficacy of the treatment between fidaxomicin and vancomycin, and results in the subgroups of CDI hypervirulent strains and recurrent CDI were obtained, but vancomycin was more effective than fidaxomicin in the treatment of severe CDI (RR = 0.94, 95% CI: 0.90-0.98, P < .01). Results showed that fidaxomicin is superior to vancomycin in terms of 40-day recurrence rate (RR = 0.52, 95% CI: 0.38-0.70, P < .01), 60-day recurrence rate (RR = 0.38, 95% CI: 0.21-0.69, P < .01) and 90-day recurrence rate (RR = 0.62, 95% CI: 0.50-0.77, P < .01). For the recurrence rate of the treatment in CDI hypervirulent strains, severe CDI and recurrent CDI, there was no significant difference between the 2 groups. In addition, there was no significant difference in the incidence of clinical adverse reactions, and same outcomes appeared in all-cause mortality at 40-day, severe CDI and recurrent CDI, but fidaxomicin was superior to vancomycin in all-cause mortality over 60-day (RR = 0.57, 95% CI: 0.34-0.96, P = .03)., Conclusion: There were no significant differences between fidaxomicin and vancomycin in the treatment of CDI in therapeutic effectiveness and adverse reactions, while fidaxomicin was superior to vancomycin in terms of recurrence rate and long-term mortality, and vancomycin is more effective in treating severe CDI., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments., Methods: This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12 weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence., Results: Four hundred seventy-six patients were considered to have CDI (320 in patients <80 years and 156 in ≥80 years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P = .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P < .001., Conclusions: No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80 years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives : Clostridioides difficile infection is a major public health issue, being among the main causes of mortality due to healthcare-associated diarrhea. This study aimed to assess the trends in mortality attributable to Clostridioides difficile infections in European countries over a period of 30 years. Materials and Methods : A descriptive epidemiological study was conducted, with the application of an ecological study design, to evaluate the trends in mortality due to Clostridioides difficile infection in the Central, Eastern, and Western European sub-regions from 1990 to 2019. The Global Burden of Disease study database was used. Trends were evaluated with the joinpoint regression analysis. Results : In both sexes, about 76% of all deaths attributable to Clostridioides difficile infections were recorded in the Western European sub-region in 2019. The age-standardized rates of the burden of Clostridioides difficile infection in 2019 were the highest in the Central European sub-region, followed by the Western European sub-region, while the lowest rates were observed in the Eastern European sub-region. A significantly increasing trend in mortality attributable to Clostridioides difficile infection from 1990 to 2019 was recorded both in males (by +2.1% per year) and females (by +2.8% per year). The burden of Clostridioides difficile infection showed increasing trends in most of the European countries, significantly correlating with the country's development, according to the Human Development Index. Conclusions : The rising burden of Clostridioides difficile infection in European countries in the last few decades suggests a need for improving public health measures, with a focus both on the hospital setting and community.

Background: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality among hospitalized patients, particularly those who are immunosuppressed. We aim to assess the outcomes of CDI among kidney transplant (KT) recipients., Methods: Nationwide Inpatient Sample from 2016 to 2020 was used to identify patients with KT and stratify based on the presence of CDI. Data were collected regarding demographics and comorbidities. Outcomes included in-hospital mortality, acute kidney injury, intensive care unit admission, transplant rejection, transplant failure, length of stay, and total hospitalization charges. The relationships between variables of interest and outcomes were analyzed using multivariate regression., Results: A total of 557,635 KT recipients were included. CDI prevalence was 2.4%. The majority of patients in the CDI group were age >65 (43.6%), female (51%), White (55.3%), and had Medicare insurance (74.9%). On multivariate regression analysis, CDI was associated with increased odds of acute kidney injury (aOR 2.06, p < 0.001), intensive care unit admission (aOR 2.47, p < 0.001), and mortality (aOR 1.90, p < 0.001). CDI was also associated with longer length of stay (9.35 days vs 5.42 days, p < 0.001) and higher total hospitalization charges ($110,063 vs $100,006, p < 0.001). There was no difference in transplant rejection, complication, failure, or infection among KT recipients with CDI and those without., Conclusions: We found that CDI was associated with worse outcomes and higher costs. KT patients should be monitored closely for signs of CDI in order to initiate appropriate management., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH., Materials and Methods: We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality., Results: The CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort., Conclusions: Patients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort., Competing Interests: Conflicts of interest None., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Objectives: Recurrent Clostridioides difficile infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus., Methods: We used data from the largest healthcare provider in Israel to identify all adults aged 18 years or older diagnosed with a first episode of CDI (Index CDI) between February 2018 and December 2022 and subsequently received a non-CDI antibiotic within 2-8 weeks. Patients who received a concurrent prophylactic CDI antibiotic constituted the CDI prophylaxis group. Multivariable Cox proportional hazard regression models were used to examine the association of secondary CDI prophylaxis with CDI recurrence according to the severity of the index CDI (primary objective) and with 4- and 8-week all-cause mortality (secondary objective)., Results: A total of 434 eligible patients were included. Among them, 327 did not receive CDI antibiotic prophylaxis, while 107 did. CDI antibiotic prophylaxis was associated with a significant risk reduction of CDI recurrence with an adjusted HR of 0.51 (95% CI, 0.27-0.97). The magnitude of the association was modified by the severity of the index CDI episode (P for interaction 0.0182). Specifically, the HR for recurrence was 0.163 (95% CI 0.045-0.593) for non-severe CDI, and 1.242 (95% CI 0.524-2.946) for severe CDI. No significant association was found between CDI antibiotic prophylaxis and 4-8 weeks mortality., Conclusion: Secondary prophylaxis with CDI antibiotics appears to be associated with a reduced risk of recurrence in patients with previous non-severe CDI episode. Further studies are needed to confirm this finding., Competing Interests: Declaration of competing interest All authors report no potential conflicts of interest., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: In the last two decades, a significant increase in the number of Clostridioides difficile infection (CDI) cases has been observed. It is understandable to attempt to determine the factors that can predict the severity of the course of the infection and identify patients at risk of death. This study aimed to analyze the factors affecting the incidence and mortality of CDI in inpatient treatment at the University Clinical Hospital in Wrocław in 2016-2018., Methods: Statistical analysis of data obtained from patients' medical records was performed. Only patients with symptoms of infection and infection confirmed by laboratory tests were enrolled in the study. When analyzing the number of deaths, only adult patients who died in hospital wards were included. The quantitative data including laboratory tests, used antibiotics and Nutritional Risk Screening (NRS) were assessed. Also, the qualitative data such as sex, year of hospitalization, occurrence of diarrhoea on admission to the hospital, presence of additional diseases, as wee ad the use of antibacterial drugs or proton pump blockers and ranitidine during hospitalization were analyzed., Results: A total of 319 adult CDI patients (178 women and 141 men) were enrolled of which 80 people died (50 women and 30 men). The mean age of the patients was 72.08 ± 16.74 years. Over the entire period studied, the morbidity was 174 cases per 100,000 hospitalizations while mortality was 25.08%. The group of deceased patients was characterized by: older age (by 9.24 years), longer duration of hospitalization (by 10 days), reduced albumin levels (Rho = -0.235, p < 0.001), higher urea levels, use of more antibiotics, higher risk of malnutrition in NRS (Rho = 0.219, p < 0.001), higher incidence of sepsis, heart failure, stroke, hypothyroidism. Pneumonia was diagnosed twice as often. It was also shown that deceased patients were significantly more likely to take penicillin and fluoroquinolones., Conclusions: In this study, the morbidity was lower, but mortality was higher compared to similar hospitals in Poland. CDI patients were characterized by older age, multimorbidity, extended hospitalization, and the use of broad-spectrum antibiotics. Risk factors for death included advanced age, prolonged hospital stays, lower albumin, higher urea, malnutrition, and comorbidities like heart failure, stroke, pneumonia, sepsis, and hypothyroidism. Increased antibiotic use, particularly penicillin and fluoroquinolones, was associated with a higher mortality risk., (© 2024. The Author(s).)

Purpose: The prevalence of Clostridioides difficile infection in older and frail population is extremely high and adverse outcomes, including future recurrences and premature mortality, are common. Nonetheless, the clinical risk profile for Clostridioides difficile recurrence in older people is still controversial. We aimed to investigate: 1) the association between Clostridioides difficile recurrence and 6-month mortality; 2) the risk factors for Clostridioides difficile recurrence after hospital discharge., Methods: This is a retrospective study on adults with a first episode of Clostridioides difficile infection admitted to all Internal Medicine and Geriatrics Units of the University Hospital of Ferrara (Italy) between January 2018 and December 2020. For each patient, sociodemographic, clinical and laboratory data were collected through hospital database system. The primary and secondary outcomes were mortality and recurrence within 6 months from the first infectious episode, respectively., Results: The mean age of the 386 enrolled patients was 77.8 years; 61.7% were females. Twelve percent patients had Clostridioides difficile recurrence and 32.1% patients died during the 6-month follow-up. At Cox analysis, after adjustment for the potential confounders, participants with recurrence reported a twofold risk of death compared to those without recurrence (HR, 95% CI 2.45, 1.59-3.78). Compared to patients treated with metronidazole, those treated with vancomycin showed a lower risk of recurrence (log-rank p < 0.001)., Conclusion: Clostridioides difficile recurrence is associated with a higher risk of mortality and it may itself be a marker of frailty and vulnerability. Vancomycin treatment during the infectious episode was associated with lower recurrence rate, as compared to metronidazole., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Clostridioides difficile infection (CDI) causes considerable morbidity, mortality, and economic cost. Advanced age, prolonged stay in healthcare facility, and exposure to antibiotics are leading risk factors for CDI. Data on CDI clinical outcomes in the very elderly patients are limited., Methods: A retrospective cohort study of patients hospitalized between 2016 and 2018 with CDI. We evaluated demographic clinical and laboratory parameters. Major clinical outcomes were evaluated including duration of hospital stay, admission to intensive care unit (ICU), in-hospital mortality, 30 days post-discharge mortality, and readmission/mortality composite outcome. We compared patients aged up to 80 years (elderly) to those of 80 years old or more (very elderly)., Results: Of 196 patients included in the study, 112 (57%) were very elderly with a mean age of 86 versus 67 years in the elderly group. The duration of hospital stays, and intensive care unit admission frequency were significantly reduced in the very elderly (13 vs. 22 days p = 0.003 and 1.8% vs. 10.7% p = 0.01, respectively). No significant difference was found in the frequencies of in-hospital and in 30 days post-discharge mortality., Conclusions: In our cohort, the duration of hospital stay seemed to be shorter in the very elderly with no increase of in-hospital and post-discharge mortality. Although admitted less frequently to ICU, the in-hospital survival of the very elderly was not adversely affected compared to the elderly, suggesting that very advanced age per se should not be a major factor to consider in determining the prognosis of a patient with CDI., (© 2024. The Author(s).)

Background: Clostridioides difficile infections (CDIs) and recurrences (rCDIs) remain a major public health challenge due to substantial mortality and associated costs. This study aims to generate real-world evidence on the mortality and economic burden of CDI in Germany using claims data between 2015 and 2019., Methods: A longitudinal and matched cohort study using retrospective data from Statutory Health Insurance (SHI) was conducted in Germany with the BKK database. Adults diagnosed with CDI in hospital and community settings between 2015 and 2018 were included in the study. Patients had a minimum follow-up of 12-months. 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 was used to assess excess mortality and incremental costs of HCRU. Up to three non-CDI patients were matched to each CDI patient., Results: A total of 9,977 CDI patients were included in the longitudinal cohort. All-cause mortality was 32%, 39% and 48% at 6-, 12-, and 24-months, respectively, with minor variations by number of rCDIs. When comparing matched CDI (n = 5,618) and non-CDI patients (n = 16,845), CDI patients had an excess mortality of 2.17, 1.35, and 0.94 deaths per 100 patient-months, respectively. HCRU and associated costs were consistently higher in CDI patients compared to non-CDI patients and increased with recurrences. Total mean and median HCRU cost per patient during follow-up was €12,893.56 and €6,050 in CDI patients, respectively, with hospitalisations representing the highest proportion of costs. A total mean incremental cost per patient of €4,101 was estimated in CDI patients compared to non-CDI patients, increasing to €13,291 in patients with ≥ 3 rCDIs., Conclusions: In this real-world study conducted in Germany, CDI was associated with increased risk of death and substantial costs to health systems due to higher HCRU, especially hospitalisations. HCRU and associated costs were exacerbated by rCDIs., (© 2024. The Author(s).)

Background: Standalone nucleic acid amplification tests (NAATs) are frequently used to diagnose Clostridioides difficile infections (CDI), although they may be unable to distinguish colonization from disease. A 2-stage algorithm pairing NAATs with toxin immunoassays (Toxin) may improve specificity. We evaluated clinical outcomes of patients who were NAAT+/Toxin+ versus NAAT+/Toxin- and treated versus untreated NAAT+/Toxin- cases through systematic review and meta-analysis., Methods: We searched EMBASE and MEDLINE from inception to April 1, 2023 for articles comparing CDI outcomes among symptomatic patients tested by NAAT and Toxin tests. The risk differences (RD) of all-cause mortality and CDI recurrence were computed by random effects meta-analysis between patients who were NAAT+/Toxin+ and NAAT+/Toxin-, as well as between patients who were NAAT+/Toxin- and treated or untreated., Results: Twenty-six observational studies comprising 12 737 patients were included. The 30-day all-cause mortality was not significantly different between those who were NAAT+/Toxin+ (8.4%) and NAAT+/Toxin- (6.7%) (RD = 0.41%, 95% confidence interval [CI] = -.67, 1.49). Recurrence at 60 days was significantly higher among patients who were NAAT+/Toxin+ (19.8%) versus NAAT+/Toxin- (11.0%) (RD = 7.65%, 95% CI = 4.60, 10.71). Among treated compared to untreated NAAT+/Toxin- cases, the all-cause 30-day mortalities were 5.0% and 12.7%, respectively (RD = -7.45%, 95% CI = -12.29, -2.60), but 60-day recurrence was not significantly different (11.6% vs 7.0%, respectively; RD = 5.25%, 95% CI -1.71, 12.22)., Conclusions: Treatment of patients who were NAAT+/Toxin- was associated with reduced all-cause mortality but not recurrence. Although subject to the inherent limitations of observational studies, these results suggest that some patients who are NAAT+/Toxin- may benefit from treatment., Competing Interests: Potential conflicts of interest. E. G. M. and T. C. L. have operating grants from the Canadian Institutes of Health Research (CIHR) and receive salary support from the Fonds de Recherche du Québec—Santé outside of this work. E. G. M. also reports a role as Board Member for WikiGuidelines for infectious diseases. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital- or community-acquired CDI, chronic comorbidities, and age., Methods: This nationwide population-based cohort study (from 2006 to 2019) compared individuals with CDI with the entire Swedish background population using standardized mortality ratios. In addition, a matched-cohort design (1:10), utilizing multivariable Poisson-regression models, provided incidence rate ratios (IRRs) with 95% CIs., Results: This study included 43 150 individuals with CDI and 355 172 controls. In total, 69.7% were ≥65 years, and 54.9% were female. CDI was associated with a 3- to 7-fold increased mortality rate (IRR = 3.5, 95% CI: 3.3-3.6; standardized mortality ratio = 6.8, 95% CI: 6.7-6.9) compared with the matched controls and Swedish background population, respectively. Mortality rates were highest for hospital-acquired CDI (IRR = 2.4, 95% CI: 1.9-3.2) and during the first CDI episode (IRR = 0.2, 95% CI: 0.2-0.3 for recurrent versus first CDI). Individuals with CDI had more chronic comorbidities than controls, yet mortality remained higher among CDI cases even after adjustment and stratification for comorbidity; CDI was associated with increased mortality (IRR = 6.1, 95% CI: 5.5-6.8), particularly among those without any chronic comorbidities., Discussion: CDI was associated with elevated all-cause and cause-specific mortality, despite possible confounding by ill health. Mortality rates were consistently increased across sexes, all age groups, and comorbidity groups., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Clostridium difficile infections (CDIs) cause significant mortality and morbidity. Critically ill patients are susceptible to CDIs and tend to have severe CDIs, and their clinical presentations are not merely diarrhea., Materials and Methods: From September 2017 to March 2018, the adults with CDIs in the ICUs were included. Fecal specimens with positive results of glutamate dehydrogenase assay were cultured for C. difficile, and toxinotyping and ribotyping for available C. difficile isolates were done. The CDI cases were categorized into the diarrheal group and ileus group. Difficult-to-treat cases with the presentations of life-threatening complications (bowel perforation or bacteremia), toxic megacolon, and refractory diarrhea, were analyzed., Results: Totally 23 cases, including 6 cases of ileus and 17 of diarrhea, were included. Overall, the incidence of CDI in the ICUs was 10.7 cases per 10,000 patient-days. The ileus group tended to have more severe presentation, shorter ICU stay, higher ICU mortality, and receive initial intravenous metronidazole therapy. Severe and fulminant CDIs accounted for 65.2% (15 cases). The ICU mortality rate was 39.1%, but only one death was directly related to CDI (4.3%). Of nine (39.1%) difficult-to-treat cases, there was only one isolate of RT611 with tcdC deletion and cdtA/cdtB from a case with toxic megacolon. No hypervirulent isolates of RT027 or 078 were detected., Conclusion: Severe CDIs in the ICU were not rare. Clinicians should be aware of abdominal symptoms and signs other than diarrhea, such as ileus, to make timely diagnosis and management of CDI., Competing Interests: Declaration of competing interest This work was supported by the grants from Ministry of Science and Technology (MOST 108-2321-B-006-004) and Ministry of Health and Welfare (MOHW 108-TDU-B-211-13303), Taiwan., (Copyright © 2020. Published by Elsevier B.V.)

Background: Among the individuals with hematological malignancy (HM) complicated with Clostridioides difficile infection (CDI), the variables associated with in-hospital mortality and recurrence of CDI were investigated., Material and Methods: Including adults with HM and those without malignancy suffering from CDI from January 2015 to December 2016 in three hospitals in Taiwan., Results: Totally 314 patients including 77 with HM and 237 patients without malignancy were included. HM patients more often had low leukocyte counts (<500 cells/mL: 28.6% vs. 2.1%) than those without malignancy and more patients without malignancy had severe CDI than patients with HM (31.6% vs. 14.3%, P = .003), according to the severity score of IDSA/SHEA. Patients with HM had a higher recurrence rate of CDI (14.3%, 11/77 vs. 7.2%, 17/237; P = .07) and longer hospital stay (47.2 ± 40.8 days vs. 33.3 ± 37.3 days; P = .006) than those without malignancy. In the multivariate analyses for those with HM and CDI, the in-hospital mortality was associated with vancomycin-resistant Enterococcus (VRE) colonization or infection (odds ratio [OR] 7.72; P = .01), and C. difficile ribotype 078 complex infection (OR 9.22; P = .03). Moreover underlying hematological malignancy (OR 2.74; P = .04) and VRE colonization/infection (OR 2.71; P = .02) were independently associated with CDI recurrence., Conclusion: Patients with HM complicated with CDI were often regarded as non-severe infection, but had a similar in-hospital mortality rate as those without malignancy. CDI due to ribotype 078 complex isolates heralded a poor prognosis among HM patients., Competing Interests: Declaration of competing interest All authors report no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Importance: Little is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients., Objective: To estimate the CDI incidence and outcomes in SOT recipients., Design, Setting, and Participants: A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period., Main Outcomes and Measures: The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis., Results: Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality., Conclusions and Relevance: In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

Background: Clostridium difficile -associated diarrhea (CDAD) is a significant cause of mortality and morbidity in hospitalized patients. Several scores have developed in order to assess the severity of CDAD., Objective: To determine the role of the serum albumin to creatinine ratio (sACR) in predicting the 30-day all-cause mortality of patients with CDAD in comparison with other known severity scores of CDAD., Methods: A retrospective study was conducted at Baruch-Padeh Medical Center from January 2014 to December 2019. Patients with CDAD were recruited from Internal Medicine Departments, Intensive Care Units, and Surgical Departments. Data on demographic characteristics, clinical signs, underlying conditions, and several risk factors for CD infection were collected. We compared between severity scores of CDAD, such as ATLAS, the CDAD severity score, and the sACR in predicting the 30-day all-cause mortality in hospitalized patients with CDAD., Results: 116 patients with CDAD were included. The ATLAS, CDAD scores, and sACR were calculated for all patients. The mean age of the participants was 71.4±16.4 years. 57.7% were of female gender. Fifty-two (44.8%) died within 30 days. An ATLAS score of ≥8 points had a 3.6-fold higher risk of 30-day all-cause mortality in hospitalized patients with CDAD (HR 3.6, 95% CI 3.28-3.99, p =0.001), a CDAD score of ≥5 points (HR 1.1, 95% CI 0.91-1.42, p =0.05), and a sACR≤3.4 (HR 1.5, 95%CI 1.25-1.82, p =0.04)., Conclusion: In this study, it was found that a sACR≤3.4 could predict the 30-day all-cause mortality in patients with CDAD., (© 2021 by the Association of Clinical Scientists, Inc.)

C. difficile infections (CDI) are increasingly recognized as a leading cause of infectious diarrhea, with increasing morbidity and mortality. Treatment primarily centers around oral vancomycin treatment. A wide range of dosing regimens exist in clinical practice, with little evidence to help distinguish the therapeutic benefit between them. This is a retrospective cohort study conducted at an academic medical center that enrolled adult patients admitted with CDI. The primary outcome was a composite of complete or partial cure at the end of treatment and was assessed using a test of equivalency with a 20% equivalency limit. Subjects were divided into low dose (125 mg) or high dose (250 mg or 500 mg) of oral vancomycin dosed every 6 hours. Overall, 78 patients were included who received low dose vancomycin and 33 who received high dose. Generally, the two groups were similar, except the low dose group had significantly more leukocytosis and less ICU admission or hypotension compared to the high dose group. Equivalency between the two treatment groups was demonstrated (Absolute Risk Difference -0.022, 90% confidence interval: -0.13 to 0.18, p = 0.03). A stepwise logistic regression identified gender, baseline albumin, and ICU admission as significant predictors of the chance for complete or partial cure. No differences between groups for the secondary outcomes of 90-day readmission/recurrence, 30-day all-cause mortality, or time to resolution of diarrhea were demonstrated. Low dose oral vancomycin was demonstrated to result in equivalent outcomes compared to high dose vancomycin for the treatment of CDI.

Background: Mesenteric venous thrombosis (MVT) is typically associated with poor prognosis. Although prophylactic antibiotics are sometimes given with the intent of limiting bacterial luminal load and translocation in patients with MVT, this approach has not been universally adopted. The aim of this study is to analyze whether utilizing antibiotics empirically in those with MVT improves patient outcomes and survival when compared to those who do not receive empiric antibiotics., Methods: A retrospective review of patients admitted with MVT between 2002 and 2019 at a single academic institution was performed. Demographics and rates of mortality need for bowel resection, readmission, and Clostridium difficile ( C. diff ) infection were compared between patients treated with empiric antibiotics and patients not treated with antibiotics., Results: Eighty-three patients (mean age 64.5 years and 55.4% male) who were admitted for MVT were included. Empiric antibiotics were utilized in 53% (n = 44) of MVT patients while 47% (n = 39) received supportive treatment without empiric antibiotics. Death occurred in 4 patients treated with antibiotics and 6 patients treated without antibiotics (9.1% vs. 15.3%, P = .50). Readmissions occurred in 12 patients (27.3%) treated with antibiotics and 10 patients (25.6%) not treated with antibiotics (27.3% vs. 25.6%, P = .87). C. diff infection occurred in 6 patients treated with antibiotics and in no patients not treated with antibiotics (13.6% vs. 0%, P = .03)., Conclusions: Empiric antibiotic usage may not improve rates of mortality or hospital readmission in patients with MVT and may unnecessarily expose patients to an increased risk of C. diff infection.

Background and Aim: Acute diverticulitis (AD) is a common gastrointestinal disease with a significant health care-associated burden. Patients hospitalized with AD have many risk factors for developing Clostridioides difficile infection (CDI). CDI is associated with poor outcomes in many diseases but has yet to be studied in AD., Methods: We utilized data from the National Inpatient Sample from January 2012 to October 2015 for patients hospitalized with AD and CDI compared with AD alone. Primary outcomes, which were mortality, length of stay, and hospitalization cost, were compared. Secondary outcomes were complications of diverticulitis and need for surgical interventions. Risk factors for mortality in AD and risk factors associated with CDI in AD patients were analyzed., Results: Among 767 850 hospitalizations for AD, 8755 also had CDI. A propensity score-matched cohort analysis demonstrated that CDI was associated with increased risk of inpatient mortality (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.30, 5.95), prolonged duration of hospitalization by 4.27 days (P < 0.0001), total hospital cost by $33 271 (P < 0.0001), need for surgery (OR 1.45, 95% CI 1.22, 1.71), and complications of diverticulitis (OR 1.45, 95% CI 1.21, 1.74). Predictors of CDI among patients with AD included female gender (1.12 OR, 95% CI 1.01, 1.24), three or more comorbidities (1.81 OR, 95% CI 1.57, 2.09), and admissions to teaching hospitals (1.44 OR, 95% CI 1.22, 1.70)., Conclusions: Clostridioides difficile infection in AD is associated with increased mortality, length of stay, and hospital cost. Preventative measures should be made for at-risk patients with AD to decrease infection rate and poor outcomes., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: The 2017 Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for Clostridioides difficile (C. difficile) infection (CDI) removed metronidazole as a preferred option for initial episodes of non-severe CDI. This study aimed to determine if the shift away from metronidazole improved clinical outcomes of initial episodes of non-severe CDI., Methods: The study was a retrospective, observational, nationwide cohort study using a Veterans Health Administration national clinical administrative database. Adult patients treated for non-severe CDI before and after the February 2018 publication of the 2017 IDSA/SHEA C. difficile Clinical Practice Guidelines were included. The primary outcome was the composite of treatment failure or probable recurrence., Results: A total of 3608 patients were included, with 1809 in the pre-guideline cohort (mean [SD] age, 65.5 [14.2] years; 1602 [88.6%] male) and 1799 in the post-guideline cohort (mean [SD] age, 64 [14.6] years; 1584 [88%] male). Overall composite of treatment failure or probable recurrence was similar between both cohorts (318 of 1809 [17.6%] pre-guideline cohort vs. 317 of 1799 [17.6%] post-guideline cohort [P = 0.97])., Conclusion: The shift away from metronidazole as a preferred option in initial non-severe Clostridioides difficile infection did not improve the composite of treatment failure or recurrence., (Published by Elsevier Ltd.)

Background: Clostridium difficile infection (CDI)-associated mortality is a major global health concern. Several clinical and laboratory parameters have been linked to poor prognosis in patients with CDI. In the current study, we aimed to assess the rate of in-hospital mortality among Israeli CDI patients and to look for clinical and laboratory parameters associated to death., Methods: We performed a multicenter retrospective study enrolling all patients above 18-years old who were hospitalized for CDI or with diagnosis made during hospitalization in two regional, teaching hospitals in the north of Israel (Galilee Medical Center, Nahariya and the Nazareth Hospital, Nazareth, Israel), from January 1, 2015 until January 1, 2020. All files of eligible patients were reviewed for demographic (age, gender), medical history and laboratory tests., Results: Overall, we included in the study 180 patients, among them 56 died in hospital due to CDI (group A) while 124 survived (group B). The average age in groups A and B was 77.02±13 vs. 71.5±19.1, respectively. On univariate analysis, several clinical and laboratory parameters were associated with in-hospital mortality, including: advanced age, renal failure, antibiotics treatment while on treatment for CDI, need for mechanical ventilation, level of hemoglobin, white blood cells (WBC) and neutrophils count, neutrophil/lymphocyte ratio, serum level of albumin, creatinine and C reactive protein. On multivariate logistic regression analysis, only 4 parameters showed statistically significant association with in-hospital mortality, including age (odds ratio [OR]: 6.97, 95%confidence interval [CI]: 4.94-8.72, P=0.003), renal failure (OR: 3.72, 95% CI: 1.22-11.24, P=0.02), WBC count (OR: 1.09, 95% CI: 1.02-1.16, P=0.008), and lower albumin level (OR: 47.62, 95% CI: 10.31-200, P<0.0001)., Conclusions: In this retrospective, multicenter study, age, serum albumin level, leucocytes count, and renal failure were the main predictors of in-hospital mortality in patients with CDI. Thus, antibiotic use should be weighed carefully in elderly comorbid patients, at increased risk of mortality from CDI .Prospective multicenter randomized studies investigating the effect of albumin infusion on in-hospital death of CDI patients are needed, thus enabling us to direct monitoring and treatment accordingly.

Background: Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging., Aims: We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA., Methods: We performed a retrospective analysis using the National Inpatient Sample, 2005-2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality., Results: The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44-1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of - 3.1% (95% CI - 5.7% to - 0.3%)., Conclusions: While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade.

Clostridiodes difficile infection (CDI) is one of the most common hospital-acquired infections with high mortality rates. Optimal management of CDI depends on early recognition of severity. However, currently, there is no acceptable standard of prediction. We reviewed severe CDI predictors in published literature and its definition according to clinical guidelines. We systematically reviewed studies describing clinical predictors for severe CDI in medical databases (Cochrane, EMBASE, Global Health Library, and MEDLINE/PubMed). They were independently evaluated by two reviewers. Six hundred thirty-three titles and abstracts were screened, and 31 studies were included. We excluded studies that were restricted to a specific patient population. There were 16 articles that examined mortality in CDI, as compared with 15 articles investigating non-mortality outcomes of CDI. The commonest risk factors identified were comorbidities, white blood cell count, serum albumin level, age, serum creatinine level and intensive care unit admission. Generally, the studies had small patient populations, were retrospective in nature, and mostly from Western centers. The commonest severe CDI criteria in clinical guidelines were raised white blood cell count, followed by low serum albumin and raised serum creatinine levels. There was no commonly agreed upon definition of severe CDI severity in the literature. Current clinical guidelines' definitions for severe CDI are heterogeneous. Hence, there is a need for prospective multi-center studies using standardized protocol for biospecimen investigation collection and shared data on outcomes of patients in order to devise a universally accepted definition for severe CDI., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Clostridioides difficile infection (CDI) is an important nosocomial infection and is the leading cause of infectious diarrhea in hospitalized patients. We aimed to assess the effect of bowel rest on the management of CDI. A single-center retrospective cohort study was conducted. The primary outcome was the composite of the all-cause mortality and CDI recurrence within 30 days. The main secondary outcome was switching from metronidazole to vancomycin. Of the 91 patients with CDI enrolled as the full cohort, 63 patients (69%) and 28 patients (31%) constituted the control group and the bowel rest group, respectively. After one-to-one propensity score matching, a total of 46 patients were included as the matched cohort. In the full cohort, the composite outcome occurred in 19.0% and 14.3% of the patients in the control and the bowel rest group, respectively (p = 0.768). In the matched cohort, it was 17.4% in each group. Although there was no statistically significant difference, the trend of switching was lower in the bowel rest group. The bowel rest may not affect the all-cause mortality and CDI recurrence within 30 days. However, in those prescribed bowel rest, switching from metronidazole to vancomycin may reduce.

Clostridium difficile is an anaerobic and spore-forming bacterium responsible for 15-25% of postantibiotic diarrhea and 95% of pseudomembranous colitis. Peptidoglycan is a crucial element of the bacterial cell wall that is exposed to the host, making it an important target for the innate immune system. The C. difficile peptidoglycan is largely N -deacetylated on its glucosamine (93% of muropeptides) through the activity of enzymes known as N -deacetylases, and this N -deacetylation modulates host-pathogen interactions, such as resistance to the bacteriolytic activity of lysozyme, virulence, and host innate immune responses. C. difficile genome analysis showed that 12 genes potentially encode N -deacetylases; however, which of these N -deacetylases are involved in peptidoglycan N- deacetylation remains unknown. Here, we report the enzymes responsible for peptidoglycan N -deacetylation and their respective regulation. Through peptidoglycan analysis of several mutants, we found that the N- deacetylases PdaV and PgdA act in synergy. Together they are responsible for the high level of peptidoglycan N -deacetylation in C. difficile and the consequent resistance to lysozyme. We also characterized a third enzyme, PgdB, as a glucosamine N -deacetylase. However, its impact on N -deacetylation and lysozyme resistance is limited, and its physiological role remains to be dissected. Finally, given the influence of peptidoglycan N -deacetylation on host defense against pathogens, we investigated the virulence and colonization ability of the mutants. Unlike what has been shown in other pathogenic bacteria, a lack of N -deacetylation in C. difficile is not linked to a decrease in virulence., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Coullon et al.)

Background: Clostridioides difficile infection (CDI) increases the risk of complications and mortality. We assessed the magnitude of these outcomes in a large cohort of English patients with initial and recurrent CDI., Aim: To compare the risk of complications and all-cause mortality, within 12 months, among hospitalized patients ≥18 years old with hospital-associated- (HA-) CDI and recurrent CDI., Methods: Patients with HA-CDI during 2002-2013 were identified using inpatient hospital data linked to primary care and death data. Each HA-CDI case was frequency matched to two hospitalized patients without CDI on age group, sex, calendar year of admission, admission method and number of hospital care episodes. A second CDI episode starting on days 13-56 was defined as recurrence. Risks of mortality and complications at 12 months were analysed using Cox proportional hazard models., Findings: We included 6862 patients with HA-CDI and 13,724 without CDI. Median age was 81.0 years (IQR 71.0-87.0). Patients with HA-CDI had more comorbidities than those without CDI, and significantly higher risks of mortality (adjusted hazard ratio (95% confidence interval) 1.77 (1.67-1.87)) and complications (1.66 (1.46-1.88)) within 12 months from hospital admission. Of those with HA-CDI, 1140 (16.6%) experienced CDI recurrence. Patients with recurrent versus non-recurrent CDI also had significantly increased risk of mortality (1.32 (1.20-1.45)) and complications (1.37 (1.01-1.84)) in the 12 months from the initial CDI., Conclusions: HA-CDI (versus no CDI) and recurrent CDI are both associated with significantly higher risks of complications or death within 12 months of the initial CDI episode., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We aimed to determine in-hospital outcomes, length of hospital stay, and resource utilization in a contemporary cohort of Clostridioides difficile infection (CDI) and vitamin D deficiency (VDD)., Methods: The National Inpatient Sample database for 2016 and 2017 was used for data analysis using International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System ( ICD-10-CM/PCS ) codes to identify the patients with the principal diagnosis of CDI and VDD. We assessed the all-cause in-hospital mortality, morbidity, length of hospital stay (LOS), and total costs between propensity-matched groups of CDI without VDD versus CDI with VDD., Results: We identified 202,234 patients with CDI, 4515 of whom were patients with VDD and 197,719 of whom were without VDD. After propensity matching, there was no difference in the in-hospital mortality between the two groups (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.58-4.3; P = 0.90). CDI with VDD has a higher odds of sepsis (OR 1.6, 95% CI 1.3-1.9; P = 0.0), and peritonitis (OR 1.6, 95% CI 1.4-3.8; P = 0.01). Mean LOS (5.9 ± 1.8 vs 5.4 ± 2, P < 0.01) and mean total charges ($11,500 vs $9971, P < 0.04) were higher in CDI with VDD. The factors affecting the LOS were acute coronary syndrome ( P = 0.04), mechanical ventilation ( P = 0.03), obesity ( P = 0.004), acute kidney injury ( P = 0.04), and sepsis ( P = 0.05)., Conclusions: In this large cohort in a propensity-matched analysis, VDD does not increase the in-hospital mortality in CDI. VDD increases the odds of complications with a higher LOS and resource utilization. These findings may be clinically relevant to guide clinicians to routinely monitor vitamin D status and supplement in patients at risk of CDI.

Data regarding extraintestinal Clostridioides difficile infections (ECDIs) remain scarce and anecdotal. We conducted a retrospective cohort study to investigate characteristics and prognostic factors in patients with ECDI. From January 1997 through December 2018, 60 patients were enrolled and divided into three groups as follows: group A (gastrointestinal [GI] disruption caused by malignancy, n = 13); group B (GI disruption from causes other than malignancy, n = 25); group C (no GI disruption, n = 22). GI disruption was defined as compromised integrity of the GI tract caused by abdominal surgery, perforation, malignancy, enterocolitis, or bleeding. The incidence of ECDI was 2.53 per 100,000 admissions. The most common specimens yielded C. difficile were blood (36.7%), peritoneal fluid (20.0%), and abscesses (16.7%). Six patients (10.0%) had confirmed C. difficile enterocolitis, and 36 patients (60.0%) had a polymicrobial infection. C. difficile bacteremia was significantly more common in group A patients than those in groups B or C (53.8% vs. 48.0% vs. 13.6%, p = 0.02), as was the 30-day mortality rate (69.2% vs. 12.0% vs. 18.2%, respectively; p < 0.001). In multivariate analysis, group A (adjusted odds ratio [aOR], 17.32; 95% confidence interval [CI], 2.96-101.21; p = 0.002) and an age of > 65 years (aOR, 7.09; 95% CI, 1.31-38.45; p = 0.02) were independent risk factors for 30-day mortality. ECDI was uncommonly associated with C. difficile enterocolitis. Two factors, GI disruption caused by malignancy, and old age, were associated with significantly poorer short-term outcomes.

The MODIFY I/II trials demonstrated that bezlotoxumab, a human monoclonal antibody against Clostridioides difficile toxin B, given during antibiotic treatment for Clostridioides difficile infection (CDI) significantly reduced C. difficile recurrence (rCDI) in adults at high risk for rCDI. Efficacy of CDI-directed intervention may depend on ribotype regional epidemiology, and patient characteristics. This post hoc analysis assessed the efficacy of bezlotoxumab in the subgroup of MODIFY I/II trial participants enrolled in Europe. Data from the bezlotoxumab (10 mg/kg single intravenous infusion) and placebo (0.9% saline) groups from MODIFY I/II were compared to assess initial clinical cure (ICC), rCDI, all-cause, and CDI-associated rehospitalizations within 30 days of discharge, and mortality through 12 weeks post-infusion. Of 1554 worldwide participants, 606 were from Europe (bezlotoxumab n = 313, 51%; placebo n = 292; 48%). Baseline characteristics were generally similar across groups, although there were more immunocompromised participants in the bezlotoxumab group (27.2%) compared with placebo (20.1%). Fifty-five percent of participants were female, and 86% were hospitalized at randomization. The rate of ICC was similar between treatment groups. The rate of rCDI in the bezlotoxumab group was lower compared with placebo among European participants overall, and among those with ≥ 1 risk factor for rCDI. Bezlotoxumab reduced 30-day CDI-associated rehospitalizations compared with placebo. These results are consistent with overall results from the MODIFY trials and demonstrate that bezlotoxumab reduces rCDI and CDI-associated rehospitalizations in European patients with CDI. MODIFY I/II (NCT01241552 and NCT01513239).

Objectives: Clostridioides difficile infections (CDI) are common in autologous (auto-HSCT) or allogenic hematopoietic stem cell transplant (allo-HSCT) recipients. However, the impact of CDI on patient outcomes is controversial. We conducted this study to examine the impact of CDI on patient outcomes., Methods: We performed a retrospective single-center study, including 191 lymphoma patients receiving an auto-HSCT and 276 acute myeloid leukemia (AML) patients receiving an allo-HSCT. The primary endpoint was overall survival (OS). Secondary endpoints were causes of death and, for the allo-HSCT cohort, GvHD- and relapse-free survival (GRFS)., Results: The prevalence of CDI was 17.6% in the AML allo-HSCT and 7.3% in the lymphoma auto-HSCT cohort. A higher prevalence of bloodstream infections, but no differences concerning OS or cause of death were found for patients with CDI in the auto-HSCT cohort. [AU] In the allo-HSCT cohort, OS and GRFS were similar between CDI and non-CDI patients. However, the leading cause of death was relapse among non-CDI patients, but it was infectious diseases in the CDI group with fewer deaths due to relapse., Conclusions: CDI was not associated with worse survival in patients receiving a hematopoietic stem cell transplantation, and there were even fewer relapse-related deaths in the AML allo-HSCT cohort., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clostridioides difficile (C.difficile) is a Gram-positive, spore-forming, toxin-producing anaerobic bacillus, which is one of the most common causes of health-care-associated infection developed mainly by elderly patients. The objective of this study was to assess mortality among the patients of the Hospital for Infectious Diseases in Warsaw related to C.difficile infection. Analysis was conducted of 1638 records reporting the medical histories of patients hospitalized for the first time due to Clostridioides difficile infection (CDI) in the Hospital for Infectious Diseases in Warsaw from 2010 to 2017. The inclusion criteria were any (principal or secondary) discharge diagnosis code for CDI according to ICD-10 and being an adult (≥ 18 years). 108 out of 1638 (7%) of the patients died. The median age in this group was 83 years. The largest number of deaths (90%) occurred in the group of patients aged 65 years or older and 81-90 years old (53% of all the deaths). In the multivariate logistic regression model relevant only to the age groups, not to sepsis-age over 80 and over 90 were independent predictors of death, increasing the risk of death by 3.4 and 1.8 times, respectively. The result of the receiver operating curve (ROC) analysis determined the age of 77 years as the threshold value, indicating the increased risk of death (AUC 0.727, standard error 0.025, 95% CI 0.678-0.776, p < 0.0001). In addition, other quantitative variables, namely CRP, creatinine and leucocytes were studied and turned out to be independent death predictors as well. The diagnosis of sepsis increased the risk of death fourfold (OR = 4.042; 95% Cl 2.4-6.7; p < 0.001). Increased inflammatory parameters, namely CRP and white blood cell count, advanced age, particularly over the age of 80, as well as a diagnosis of sepsis are independent risk factors for death and could be used as predictive markers of poor outcome in CDI.

The purpose of the present study was to determine whether a correlation existed between chick mortality and the presence of Clostridium perfringens alpha-toxin and NetB-toxin genes (cpa and netB) in C. perfringens recovered from litter in commercial broiler houses. Because coccidiosis predisposes chickens to necrotic enteritis, the concentration of Eimeria oocysts in these samples was measured, and the numbers were used in similar correlation analyses. Litter samples were collected at 0, 2, and 4 wk growout from six broiler farms (18 houses total) during an anticoccidial drug (ACD) control program and from nine broiler farms (23 houses total) during an Eimeria vaccine (VAC) control program. Of these, litter samples were collected from five farms during both ACD and VAC programs. The litter samples were processed for Eimeria oocyst and C. perfringens spore enumerations by standard parasitologic and microbiologic techniques. DNA was also extracted for C. perfringens DNA for PCR detection of genes coding for alpha- and NetB-toxin. A general trend during the ACD programs was a transient decrease in both Eimeria maxima and non-E. maxima (Eamipt) numbers at 2 wk growout. The pattern was slightly different during VAC with E. maxima and Eamipt levels increasing over time. Average concentrations of C. perfringens in litter were highest at 2 wk (∼105-106 spores/g) during ACD and at placement during VAC (∼105-106 spores/g). During the ACD program, a strong correlation was observed between 0 and 3-wk chick mortality and the presence at placement (0 wk) of netB (r = 0.42-0.48) or cpa (r = 0.55-0.67). A very strong correlation was observed in 0-5-wk chick mortality and the presence of netB at 4 wk growout (0.73-0.95). During a VAC program, a strong correlation was only observed between the presence of netB at placement and 0-1-wk chick mortality (r = 0.67).

Objective: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and associated with high morbidity and mortality. As current guidelines recommend treatment stratified for disease severity, this study aimed to identify predictors of 30-day mortality in order to develop a robust prediction model., Design: This was a retrospective analysis of 207 inpatients with CDI who were treated at the Jena University Hospital between September 2011 and December 2015. In a training cohort (n=127), predictors of 30-day mortality were identified by receiver operating characteristics analysis and logistic regression. The derived model was validated in an independent cohort of 80 inpatients with CDI., Results: Within 30 days, 35 (28%) patients in the training cohort died from any cause. C-reactive protein (CRP) of ≥121 mg/L (OR 3.80; 95% CI 1.64 to 7.80; p=0.003) and lower systolic blood pressure of ≤104 mm Hg (OR 3.73; 95% CI 1.63 to 8.53; p=0.002) at diagnosis as well as development of renal impairment (serum creatinine >1.5×baseline; OR 5.61; 95% CI 1.94 to 16.26; p=0.035) within the first 6 days were associated with 30-day mortality in univariate analysis. The use of these parameters enabled correct mortality prediction in 73% of cases on the day of diagnosis and in 76% at day 6. In the validation cohort, 30-day mortality was 18/80 (23%). Our model enabled a 73.7% correct prediction concerning 30-day mortality on day 6 after diagnosis of CDI., Conclusion: Hypotension and CRP elevation on the day of diagnosis as well as occurrence of kidney dysfunction during the first 6 days are suitable parameters to predict 30-day mortality in patients with CDI who need to be treated in the hospital., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clostridioides (Clostridium) difficile is the main etiology underlying antibiotic-associated diarrhea (AAD). Still, few Brazilian data are available on this infection. The aims of this multicenter study were to identify the prevalence, clinical characteristics, and outcomes of C. difficile infection (CDI) in patients with antibiotic associated diarrhea at eight hospitals in Curitiba, southern Brazil, during the years 2017-2019. Stool samples were tested using enzyme immunoassay for glutamate dehydrogenase antigen (GDH) and A/B toxins. Positive GDH samples were further evaluated by real-time polymerase chain reaction (PCR) for the presence of genes encoding toxin B (tcdB), binary toxin (cdt), and marker of hypervirulent C. difficile strain (tcdC deletion). The prevalence of CDI in 351 patients with AAD included in the study was 17.7% (n = 62). Among the CDI cases, tcdB was positive in all 62 stool samples, while cdt was positive in 10 samples, and tcdC deletion was positive in only two. Carriage of carbapenem-resistant Gram-negative bacilli, previous hospitalization, and use of broad-spectrum cephalosporin and carbapenem were associated with CDI. Among patients with CDI, 64.5% presented with severe diarrhea, and 8% (5/62) progressed with colitis and required intensive care. The 30-day mortality was 24% (15/62), and the CDI-associated mortality was 4.8% (3/62). Overall, 83.8% (52/62) of the patients achieved primary cure, and 20.8% of the evaluated patients (10/48) presented CDI recurrence. The treatment administered was not significantly associated with the 60-day recurrence or mortality. In conclusion, we reported in this study data of prevalence and recurrence rates of CDI in patients with AAD and evaluated the number of severe cases and infection-related mortality, which were up to now unknown in Southern Brazilian hospitals., Competing Interests: Declaration of competing interest All the authors there are no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Although Clostridioides difficile -associated diseases (CDAD) is considered to be associated with colitis in horses, few studies have been performed with a focus on the characteristics of CDAD in thoroughbred racehorses., Methods: Between 2010 and 2018, a test for C. difficile was performed using faecal samples from 137 thoroughbred racehorses with colitis presenting with diarrhoea and fever. The mortality rate, clinical findings, predisposing factors and the selected treatments were investigated in a retrospective manner., Results: Twenty-four cases were diagnosed as CDAD and 113 as non-CDAD. The mortality rate was significantly higher in the CDAD group (83 per cent) than that in the non-CDAD group (34 per cent). The levels of serum amyloid A, blood urea nitrogen and packed cell volume at initial presentation were also significantly higher, and those of total protein and albumin were significantly lower in the CDAD group. The development of CDAD was associated with the administration of antimicrobials, surgery and hospitalisation. No significant improvement in mortality was observed for any of the selected treatment in both groups., Conclusion: CDAD in thoroughbred racehorses was identified as a high mortality disease with rapid progression of systemic inflammation and deterioration of the circulatory state. Further investigation is required to improve the treatment., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the relationship between Clostridium (Clostridioides) difficile strain characteristics and C. difficile infection (CDI) outcome., Methods: Between October and December 2017, 16 hospitals collected epidemiological data according to the European Centre for Disease Prevention and Control (ECDC) surveillance protocol for CDI. C. difficile isolates were characterized by ribotyping, toxin genes detection and antibiotic susceptibility testing to metronidazole, vancomycin and moxifloxacin., Results: The overall mean CDI incidence density was 4.5 [95% CI 3.6-5.3] cases per 10,000 patient-days. From the 433 CDI cases, 330 (76.2%) were healthcare-associated, 52 (12.0%) cases were community-associated or of unknown origin and 51 (11.8%) CDI cases recurrent; a complicated course of CDI was reported in 65 cases (15.0%). Eighty-eight (20.3%) of patients died and 59 of them within 30 days after the CDI diagnosis. From the 379 C. difficile isolates, the most prevalent PCR ribotypes were 001 (n = 127, 33.5%) and 176 (n = 44, 11.6%). A total of 186 (49.1%) isolates showed a reduced susceptibility to moxifloxacin (> 4 mg/L) and 96.4% of them had Thr82Ile in the GyrA. Nineteen isolates revealed reduced susceptibility to metronidazole and two isolates to vancomycin (> 2 mg/L). A fatal outcome was associated with a reduced susceptibility to moxifloxacin, the advanced age of the patients and a complicated course of CDI (p<0.05). No association between ribotype, binary toxin and a reduced susceptibility to moxifloxacin and complicated course or recurrent CDI was found., Conclusions: A reduced susceptibility to moxifloxacin, in causative C. difficile strains was associated with fatal outcome of the patients, therefore it is an important marker in surveillance of CDI.

Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Clostridioides difficile is an enteric pathogen that can cause significant clinical disease in both humans and animals. However, clinical disease arises most commonly after treatment with broad-spectrum antibiotics. The organism's ability to cause naturally occurring disease in mice is rare, and little is known about its clinical significance in highly immunocompromised mice. We report on 2 outbreaks of diarrhea associated with C. difficile in mice. In outbreak 1, 182 of approximately 2, 400 NOD.Cg- Prkdc scid Il2rg tm1Wjl /SzJ (NSG) and related strains of mice became clinically ill after cessation of a 14-d course of 0.12% amoxicillin feed to control an increase in clinical signs associated with Corynebacterium bovis infection. Most mice had been engrafted with human tumors; the remainder were experimentally naïve. Affected animals exhibited 1 of 3 clinical syndromes: 1) peracute death; 2) severe diarrhea leading to euthanasia or death; or 3) mild to moderate diarrhea followed by recovery. A given cage could contain both affected and unaffected mice. Outbreak 2 involved a small breeding colony (approximately 50 mice) of NOD. CB17- Prkdc scid /NCrCrl (NOD- scid ) mice that had not received antibiotics or experimental manipulations. In both outbreaks, C. difficile was isolated, and toxins A and B were detected in intestinal content or feces. Histopathologic lesions highly suggestive of C. difficile enterotoxemia included fibrinonecrotizing and neutrophilic typhlocolitis with characteristic 'volcano' erosions or pseudomembrane formation. Genomic analysis of 4 isolates (3 from outbreak 1 and 1 from outbreak 2) revealed that these isolates were closely related to a pathogenic human isolate, CD 196. To our knowledge, this report is the first to describe naturally occurring outbreaks of C. difficile -associated typhlocolitis with significant morbidity and mortality in highly immunocompromised strains of mice.

Background: A syndromic gastrointestinal pathogen panel (GIP) was implemented in May 2018. All positive (+) GIP and standard-of-care (SOC) C. difficile results were reviewed., Methods: A single-center audit of adult patients with GIP results was conducted May-December 2018. We reviewed GIP(+)/SOC(+/-) and GIP(-)/SOC(-) tests (control group) for clinical outcomes., Results: We reviewed 269 GIP(+) patients. Of 119 GIP(+)/SOC(+) patients, 44 (37%) were positive by toxin A/B enzyme immunoassay, and 75 (63%) by PCR only. Thirty-day mortality and re-admission were not significantly different between groups. CDI rates within 6 months were not significantly different between GIP(+)/SOC(-) and controls (p-value = 0.39). Those with initial SOC(+) tests had more true CDI events within 6 months, compared to controls (p-values < 0.001)., Conclusions: Forty percent of patients with GIP(+) C. difficile were (-) by SOC test, suggesting that true CDI was not present. Additional PCR-based testing may not impact outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P  ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment. IMPORTANCE Clostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis., (Copyright © 2020 Abhyankar et al.)

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., (Copyright © 2020 Dieterle et al.)

Background: Data on the impact of combination therapy (intravenous metronidazole [IV MTZ] plus oral vancomycin [PO VAN]) on clinical outcomes in intensive care unit (ICU) patients with severe non-fulminant Clostridioides difficile infection (CDI), including NAP1-positive samples, are lacking., Methods: Retrospective observational cohort of adult patients who developed CDI in the ICU diagnosed with severe non-fulminant CDI who received PO VAN. Patients with an order for IV MTZ started within 72 hours of PO VAN and who received at least 72 hours of combined therapy composed the combination therapy group. A subset of patients had stool samples collected for NAP1 testing. An additional subset was matched by Acute Physiology and Chronic Health Evaluation (APACHE) II scores. The primary outcome was inpatient all-cause mortality within 30 days of CDI diagnosis., Results: A total of 138 patients were included with 60 (43.5%) patients in the combination group. Compared with the PO VAN group, those in the combination group had higher white blood cell counts at diagnosis (15.9 [interquartile range (IQR) 10.2-21.1] vs 20.9 [IQR 16.2-29] cells/mm 3 , p<0.001), respectively. Overall inpatient mortality was higher in the combination group, but 30-day mortality was not significantly different between groups (12.8% monotherapy vs 18.3% combination, p=0.371). This finding was the same for the 96 patients in the APACHE II-matched subgroup, 14.6% monotherapy versus 18.8% combination, p=0.785. NAP1 testing was completed in 42 patients; 11 were positive (26.2%). Patients who were NAP1 positive were more likely to receive IV MTZ (54.5% vs 19.4%, p=0.026)., Conclusion: Compared with PO VAN, combination therapy with IV MTZ was not associated with better clinical outcomes in severe non-fulminant CDI in ICU patients., (© 2020 Pharmacotherapy Publications, Inc.)

Introduction : Up to 15% of hospitalized patients with Clostridioides difficile infection (CDI) develop severe CDI (SCDI) or Fulminant CDI (FCDI). Due to high rates of mortality in medically-refractory CDI cases, 30% of patients with severe infection historically require surgical intervention. However, colectomy itself is an imperfect solution because it is difficult to predict who will fail medical therapy, patients with SCDI are more likely to have underlying medical conditions that make them poor surgical candidates, and post-surgical mortality still approaches 30-50%. Areas covered : This review will serve as a clinically-based review of severe and fulminant CDI management including discussion of models to predict severe infection, emerging treatments, novel targets for therapy, and innovations in surgical management. Expert opinion : Among the most promising studies to emerge in the last decade have involved fecal microbiota transplantation (FMT), which is already recommended by multiple society guidelines for recurrent CDI (RCDI). In the case of SCDI/FCDI, multiple studies have safely and successfully utilized FMT to produce rates of cure in the 70-90% range. Additionally, patients who have FCDI refractory to medical therapy and are poor candidates for colectomy may benefit from FMT as salvage therapy.

Clostridioides (Clostridium) difficile infection (CDI) is the leading cause of infectious diarrhoea in hospitalised patients, representing a substantial economic burden driven mainly by increased length of hospital stay (LoS). Currently in Japan, limited evidence on CDI-associated excess LoS is available. We conducted a retrospective, matched-cohort study using a large, Japanese, hospital-based administrative database. CDI was defined as CDI treatment plus either CDI diagnosis or positive enzyme immunoassay result. Propensity score matching at the time of CDI or recurrent CDI (rCDI) onset was applied to adjust baseline confounding and immortal time bias. The analysis included 5 994 054 hospitalisation records during 2008-2017, of which 11 823 were identified as CDI and 1359 as rCDI. The median excess LoS attributable to CDI and rCDI was 3 days and 6.5 days, respectively. The excess mortality attributable to CDI was 6.9%; there was no excess mortality attributable to rCDI (-1.9%). The median difference in costs attributable to CDI and rCDI during the residual stay was JPY 130 296 (USD 1185) and JPY 81 054 (USD 737) per hospitalisation, respectively. By adjusting the biases, the burden of CDI in Japan was evaluated. The findings could support decision making and resource allocation for CDI management in Japanese hospitals.

Background: Although population characteristics and antimicrobial prescribing practices suggest that the hospitalized population in Japan is at high risk of Clostridioides difficile infection (CDI), the epidemiology of CDI in Japan is poorly understood., Aim: This prospective cohort study aimed to investigate the epidemiology of CDI at 12 hospitals in Japan., Methods: Patients with clinically significant diarrhoea (CSD) were enrolled. Stool specimens were tested for C. difficile by toxin A and/or B enzyme immunoassay (EIA) in the hospital laboratories, and a toxigenic culture and nucleic acid amplification tests were performed at a central laboratory. The risk factors of CDI and the impact of CDI on mortality were investigated., Findings: In total, 566 patients with CSD were included in the analyses. A total of 152 patients received the diagnosis of CDI by Toxin A/B EIA, toxigenic culture, or nucleic acid amplification test. Factors associated with CDI included low albumin (adjusted odds ratio (aOR): 1.56; 95% confidence interval (CI): 1.03-2.34) and length of hospital stay before stool collection >18 days (aOR: 1.73; 95% CI: 1.09-2.75). CDI was associated with an increased mortality on univariate analysis (OR: 1.6, 95% CI: 1.0-2.6) but was not associated with an increased risk of mortality on multivariable analysis., Conclusion: Risk factors for CDI in Japan were similar to those identified in the USA and Europe. However, CDI was not associated with an increased risk of mortality in this population of patients with CSD., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)