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.

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.

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.

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.

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.

Association of Clostridioides difficile with adverse clinical outcomes in patients with acute diverticulitis: A nationwide study.

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.

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.

Predictors of in-hospital mortality among patients with clostridium difficile infection: a multicenter study.

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.

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.

A preliminary study of bowel rest strategy in the management of Clostridioides difficile infection.

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.

Correlation Between Clostridium perfringens Alpha- and NetB-Toxin and Chick Mortality in Commercial Broiler Farms During Different Anticoccidial Control Programs.

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).

Outcomes of Clostridioides difficile in Patients with Vitamin D Deficiency: A Propensity-Matched National Inpatient Sample Analysis.

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.

Advanced age and increased CRP concentration are independent risk factors associated with Clostridioides difficile infection mortality.

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.

Development and validation of a simple and robust model to predict 30-day mortality in patients with Clostridioides difficile-associated enterocolitis.

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.

Peptidoglycan analysis reveals that synergistic deacetylase activity in vegetative Clostridium difficile impacts the host response.

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.

Risk of complications and mortality following recurrent and non-recurrent Clostridioides difficile infection: a retrospective observational database study in England.

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.