Is advanced age still a risk factor for recurrence of C. difficile infection in the era of new treatments?

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.

Efficacy of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection: A systematic meta-analysis.

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.

The global burden and trend of Clostridioides difficile and its association with world antibiotic consumption, 1990-2019.

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.

Mortality in clostridioides difficile infection among patients hospitalized at the university clinical hospital in Wroclaw, Poland - a 3-year observational study.

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 Wroclaw 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.

Secondary prophylaxis for Clostridioides difficile infection for patients on non-C. difficile antibiotics: a retrospective cohort study.

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.

Outcomes and risk factors for mortality in clostridioides difficile infection in patients with NAFLD and NASH.

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.

Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: the RECUR Germany study.

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.

Clinical outcomes of clostridioides difficile infection in the very elderly.

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.

Recurrence of Clostridioides difficile infection and mortality in older inpatients.

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.

The impact of Clostridioides difficile infection on outcomes among kidney transplant recipients.

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.

Incidence and Outcomes Associated With Clostridioides difficile Infection in Solid Organ Transplant Recipients.

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.

Serum Albumin to Creatinine Ratio as Predictor for 30-Day All-Cause Mortality in Patients with Clostridium Di!cile-Associated Diarrhea.

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.

Clostridioides difficile infection in patients with hematological malignancy: A multicenter study in Taiwan.

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.

Outcomes associated with recent guideline recommendations removing metronidazole for treatment of non-severe Clostridioides difficile infection: a retrospective, observational, nationwide cohort study.

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.

Trends in Hospitalizations for Clostridioides difficile Infection in End-Stage Liver Disease, 2005-2014.

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.

Patient Outcomes in Mesenteric Venous Thrombosis Treated With Empiric Antibiotics.

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.

Severe Clostridium difficile infections in intensive care units: Diverse clinical presentations.

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.

Optimal vancomycin dose in the treatment of Clostridium difficile infection, antimicrobial stewardship initiative.

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.

Systematic review on the definition and predictors of severe Clostridiodes difficile infection.

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.