Clostridioides Difficile Infection Episode Research Articles

Are Patients Preferentially Receiving Oral Vancomycin for Clostridioides difficile Infection in 2018? A Population Perspective

Background: Historically, metronidazole was first-line therapy for Clostridioides difficile infection (CDI). In February 2018, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) updated clinical practice guidelines for CDI. The new guidelines recommend oral vancomycin or fidaxomicin for treatment of initial episode of CDI in adults. We examined the changes in treatment of CDI during 2018 across all types of healthcare settings in metropolitan Atlanta. Methods: Cases were identified through the Georgia Emerging Infections program (funded by the Centers for Disease Control and Prevention), which conducts active population-based surveillance in an 8-county area including Atlanta, Georgia (population, 4,126,399). An incident case was a resident of the catchment area with a positive C. difficile toxin test and no additional positive test in the previous 8 weeks. Recurrent CDI was defined as >1 incident CDI episode in 1 year. Clinical and treatment data were abstracted on a random 33% sample of adult (>17 years) cases. Definitive treatment categories were defined as the single antibiotic agent, metronidazole or vancomycin, used to complete a course. We examined the effect of time of infection, location of treatment, and number of CDI episodes on the use of metronidazole only. Results: We analyzed treatment information for 831 adult sampled cases. Overall, cases were treated at 29 hospitals (568 cases), 4 nursing homes (6 cases), and 101 outpatient providers (257 cases). The mean age was 60 (IQR, 34–86), and 111 (13.4%) had recurrent infection. Moreover, ∼28% of first-incident CDI episodes, 8% of second episodes, and 6% of third episodes were treated with metronidazole only. Compared to facility-based providers, outpatient providers were more likely to treat initial CDI episodes with metronidazole only (44% vs 21%; relative risk [RR], 2.1; 95% CI, 1.7–2.7). Treatment changed over time from 56% metronidazole only in January to 10% in December (Fig. 1). First-incident cases in the first quarter of 2018 were more likely to be treated with metronidazole only compared to those in the fourth quarter (RR, 2.76; 95% CI, 1.91–3.97). Conclusions: Preferential use of vancomycin for initial CDI episodes increased throughout 2018 but remained <100%. CDI episodes treated in the outpatient setting and nonrecurrent episodes were more likely to be treated with metronidazole only. Additional studies on persistent barriers to prescribing oral vancomycin, such as cost, are warranted.Funding: NoneDisclosures: Scott Fridkin reports that his spouse receives a consulting fee from the vaccine industry.

S0745 SComparing Recurrence Rates of Clostridioides difficile Infection (CDI) for Patients With Inflammatory Bowel Disease After Long vs Short-Term Oral Vancomycin for Initial Episode of CDI

INTRODUCTION: Patients (pts) with IBD are at increased risk of Clostridioides difficile infection (CDI) and its associated morbidity and mortality. First line treatment (tx) of CDI is oral vancomycin (OV). Specific guidelines do not exist for CDI tx in IBD pts and studies have not definitively shown whether initial long-term OV reduces the rate of recurrent CDI (rCDI). This study compares rCDI rates following long-term OV versus short-term OV as tx for the first episode of CDI. METHODS: We retrospectively reviewed 878 patient records in an existing database of IBD pts between 11/1/2016 and 2/28/2019 to identify those with a history (hx) of CDI. The following data was obtained: baseline demographics, tx of first CDI, and rCDI. Short-term OV was defined as 10-14 days of tx, and long-term OV was a taper of at least 4 weeks; the length of OV tx was based on physician discretion. Categorical variables were analyzed using the Chi-Square test. RESULTS: 78 pts (8.9% of the total cohort, 57% female, median age 21 yrs [range 4–66] at IBD diagnosis) with hx of CDI were identified; 47 pts had data available to identify the prescribed antibiotic and the length of tx for their first CDI episode (Table 1). 24 pts (51%) had initial tx with short-term OV and 14 pts (30%) with a long-term OV. 4 pts in both the short-term and long-term OV groups received concomitant metronidazole (MTZ); thus a total of 8 pts received concomitant MTZ. The remaining 9 pts were treated with MTZ alone. 12 pts (50%) treated with short-term OV and 5 pts (36%) treated with long-term OV developed rCDI. rCDI in those with short-term OV was not significantly different from those with long-term OV (50% vs 36%, P = 0.39); there was no difference between those with CD or UC (P = 0.13 and 0.82, respectively) in terms of tx length and rCDI. Smoking (OR = 0.70, 95% CI [0.15–3.07], P = 0.59) was not associated with increased odds of rCDI. Long-term OV (OR = 0.59 [0.13–2.52], P = 0.42) and concomitant use of MTZ (OR = 0.33 [0.03–2.34], P = 0.21) were not associated with decreased odds of rCDI (Table 2). CONCLUSION: In pts with available antibiotic data, our study shows that there was no difference in rCDI following short-term OV and long-term OV as tx for the first episode of CDI; this may have been due to a small sample size as there was a lower percentage of rCDI in those with long-term OV. Long-term OV or concomitant MTZ did not decrease odds of rCDI. Further prospective study in a larger cohort of pts is warranted to validate these findings.Table 1.: Demographic Data and Clostridioides difficile Recurrence DataTable 2.: Statistical Analysis

Recurrent Clostridioides difficile infection can be predicted using inflammatory mediator and toxin activity levels

Background:Clostridioides difficile infection (CDI) frequently recurs after initial treatment. Predicting recurrent CDI (rCDI) early in the disease course can assist clinicians in their decision making and improve outcomes. However, predictions based on clinical criteria alone are not accurate and/or do not validate other results. Here, we tested the hypothesis that circulating and stool-derived inflammatory mediators predict rCDI. Methods: Consecutive subjects with available specimens at diagnosis were included if they tested positive for toxigenic C. difficile (+enzyme immunoassay [EIA] for glutamate dehydrogenase and toxins A/B, with reflex to PCR for the tcdB gene for discordants). Stool was thawed on ice, diluted 1:1 in PBS with protease inhibitor, centrifuged, and used immediately. A 17-plex panel of inflammatory mediators was run on a Luminex 200 machine using a custom antibody-linked bead array. Prior to analysis, all measurements were normalized and log-transformed. Stool toxin activity levels were quantified using a custom cell-culture assay. Recurrence was defined as a second episode of CDI within 100 days. Ordination characterized variation in the panel between outcomes, tested with a permutational, multivariate ANOVA. Machine learning via elastic net regression with 100 iterations of 5-fold cross validation selected the optimal model and the area under the receiver operator characteristic curve (AuROC) was computed. Sensitivity analyses excluding those that died and/or lived >100 km away were performed. Results: We included 186 subjects, with 95 women (51.1%) and average age of 55.9 years (±20). More patients were diagnosed by PCR than toxin EIA (170 vs 55, respectively). Death, rCDI, and no rCDI occurred in 32 (17.2%), 36 (19.4%), and 118 (63.4%) subjects, respectively. Ordination revealed that the serum panel was associated with rCDI (P = .007) but the stool panel was not. Serum procalcitonin, IL-8, IL-6, CCL5, and EGF were associated with recurrence. The machine-learning models using the serum panel predicted rCDI with AuROCs between 0.74 and 0.8 (Fig. 1). No stool inflammatory mediators independently predicted rCDI. However, stool IL-8 interacted with toxin activity to predict rCDI (Fig. 2). These results did not change significantly upon sensitivity analysis. Conclusions: A panel of serum inflammatory mediators predicted rCDI with up to 80% accuracy, but the stool panel alone was less successful. Incorporating toxin activity levels alongside inflammatory mediator measurements is a novel, promising approach to studying stool-derived biomarkers of rCDI. This approach revealed that stool IL-8 is a potential biomarker for rCDI. These results need to be confirmed both with a larger dataset and after adjustment for clinical covariates.Funding: NoneDisclosure: Vincent Young is a consultant for Bio-K+ International, Pantheryx, and Vedanta Biosciences.

Time trends and predictors of laboratory-confirmed recurrent and severe Clostridioides difficile infections in Manitoba: a population-based study.

Many previous studies of Clostridioides difficile infection (CDI) epidemiology have used hospital discharge data codes, which can have limited accuracy. We used a data set of laboratory-confirmed cases of CDI in the province of Manitoba, Canada, to describe the epidemiology of CDI over a decade. We conducted a population-based historical cohort study using Manitoba Health's population-wide laboratory-based CDI data set linked to administrative health databases. All individuals living in Manitoba and experiencing a CDI episode between 2005 and 2015 were included (n = 8471) and followed up from CDI diagnosis. We assessed time trends of CDI, incidence and predictors of recurrence and severe outcomes, and health care encounters after CDI diagnosis. CDI episodes were stratified by community versus hospital site of acquiring CDI. Between 2005 and 2009, overall CDI diagnoses decreased by an average of 12.6% per year (95% confidence interval [CI] -4.4 to -20.0), with no statistically significant change from 2010 to 2015. In stratified analysis, incident and recurrent CDI had a similar decrease in the initial study time period and then stabilized. The proportion of community-associated CDI cases increased by an average of 4.8% per year (95% CI 2.8 to 6.8) during the study period. CDI acquired in a health care facility had a higher recurrence rate and more severe outcomes. Recurrence of CDI increased the likelihood of admission to hospital. Between 2005 and 2015, the rates of overall laboratory-confirmed CDI, incident CDI, recurrent CDI and severe outcomes following CDI initially decreased before stabilizing, and an increasing proportion of CDI cases were community-associated. There is an increasing need to test for CDI among outpatients with diarrhea and to increase efforts to prevent recurrent CDI.

Durability of Response to Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence in Patients With Clostridioides difficile Infection.

Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI. We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. Overall, 460 patients were included (median age, 57 years [18-94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%-84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15-.49; P < .001). The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.

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

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. 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. 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. 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. 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.

Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection

Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection

Cost burden of Clostridioides difficile infection to the health service: A retrospective cohort study in Scotland

Clostridioides difficile infection (CDI) is associated with high healthcare demands and related costs. To evaluate the healthcare and economic burden of CDI in hospitalized patients with community- (HOCA-CDI) or hospital-associated CDI (HOHA-CDI) in the National Health Service in Scotland. A retrospective cohort study was conducted, examining data between August 2010 and July 2013 from four patient-level Scottish datasets, linked to death data. Data examined included prior antimicrobial prescriptions in the community, hospitalizations, length of stay and mortality. Each CDI case was matched to three hospital-based controls on the basis of age, gender, hospital and date of admission. Descriptive economic evaluations were based on bed-day costs for different types of wards. Overall, 3304 CDI cases were included in the study. CDI was associated with additional median lengths of stay of 7.2 days for HOCA-CDI and 12.0 days for HOHA-CDI compared with their respective, matched controls. The 30-day mortality rate was 6.8% for HOCA-CDI and 12.4% for HOHA-CDI. Overall, recurrence within 90 days of the first CDI episode occurred in 373/2740 (13.6%) survivors. The median additional expenditure for each initial CDI case compared with matched controls was £1713. In the 6 months after the index hospitalization, the cost associated with a CDI case was £5126 higher than for controls. Using routinely collected national data, we demonstrated the substantial burden of CDI on healthcare services, including lengthy hospital stays and readmissions, which increased the costs of managing patients with CDI compared with matched controls.

Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort. A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month. Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy. Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.

Analysis of predisposing factors for the development of Clostridioides difficile infection recurrence.

AbstractThe purpose of this study is to evaluate the influence of several risk factors and, among them, the role of different types of antibiotics, in the development of the first recurrent episode of Clostridioides difficile (CD) infection. We performed a case control study from 2006 to 2016. We included patients admitted to the hospital with CD infection that received any antibiotic treatment during the year before the onset of the infection. First, we described the characteristics of CD infection in a Spanish third level hospital and then we compared first cases of CD infection that presented recurrence with those that did not. We included 110 cases, corresponding to 94 individuals. There were 14 first CD infection episodes that later presented recurrence (12.7%). Receiving more than 3 types of antibiotics during the year before the onset of symptoms was associated with higher risk of presenting a recurrent episode (OR = 4.69, 95% CI 1.01-21.78), as well as the past history of neoplasia (OR = 4.58, 95% CI 1.00-20.98). The number of previous hospital admissions was associated with the development of recurrences in the univariate study (p < 0.05). No differences were observed related to the type of antibiotic used immediately before the CD episode neither with the treatment received. The number of types of antibiotics used during the year before the first episode of CD infection or having a personal history of neoplasia was associated with 4 times higher risk of recurrent episodes. Type of antibiotic used did not show to influence recurrences.

Recurrent Clostridioides difficile infection: Recognition, management, prevention.

Clostridioides difficile infection (CDI) is the most common cause of diarrhea in hospitalized patients and results in substantial morbidity, mortality, and costs. Its clinical management, primarily with antibiotics, is often complicated by recurrent episodes. These recurrent CDI episodes are thought to be caused by antibiotic disruption of colonic microbiota and usually occur within 4 weeks of completing antibiotic therapy. The risk of recurrent CDI increases after the first episode, creating a need for management strategies to diagnose, treat, and prevent these complications.

Real-world Experience of Bezlotoxumab for Prevention of Clostridioides difficile Infection: A Retrospective Multicenter Cohort Study.

BackgroundBezlotoxumab is approved for prevention of recurrence of Clostridioides difficile infection (CDI) in adults receiving standard of care (SoC) therapy based on findings from MODIFY clinical trials. However, utilization practices and validation of trial results in the real world are limited.MethodsRecords of patients receiving bezlotoxumab between April 2017 and December 2018 across 34 infusion centers in the United States were retrospectively reviewed. Recurrent CDI (rCDI), defined as diarrhea lasting ≥2 days resulting in treatment, was assessed 90 days postbezlotoxumab.ResultsThe study cohort included 200 patients (median age, 70 years; 66% female; median Charlson comorbidity index, 5), of whom 86% (n = 173) had prior CDI episodes and 79% (n = 158) had ≥2 risk factors for rCDI. SoC antibiotics included vancomycin (n = 137, 68%), fidaxomicin (n = 60, 30%), and metronidazole (n = 3, 2%). Median time from C. difficile stool test to bezlotoxumab and initiation of SoC to bezlotoxumab were 15 days and 11 days, respectively. Within 90 days, 31 of 195 patients (15.9%) experienced rCDI, which corresponds to a success rate of 84.1%. Patients with ≥2 CDI recurrences prebezlotoxumab had a higher risk of subsequent rCDI compared with those with 1 recurrence or primary CDI (hazard ratio, 2.77; 95% confidence interval, 1.14–6.76; P = .025).ConclusionsThis real-world multicenter study demonstrated successful prevention of rCDI with bezlotoxumab comparable to clinical trial results regardless of type of SoC and timing of infusion. Multiple prior CDI recurrences were associated with a higher risk of subsequent rCDI, supporting the use of bezlotoxumab earlier in the disease course.

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) wereidentified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.

A100 ORAL VANCOMYCIN THERAPY FOR CLOSTRIDIOIDES DIFFICILE INFECTION AND RISK OF INFECTION WITH GRAM-NEGATIVE ORGANISMS

Abstract Background Vancomycin is the recommended first-line therapy for mild to severe Clostridioides difficile infection (CDI). However, oral vancomycin is associated with disruption of the indigenous microbiota, predisposing patients to overgrowth of endogenous pathogens such as vancomycin-resistant enterococci. Aims The primary objective of the study is to examine the effect of the treatment regimens of CDI on the risk of infection with gram-negative organisms in adult patients treated for CDI. Methods A retrospective cohort study of 319 adult patients treated for CDI at Hamilton Health Sciences in the year 2015. A multivariate logistic regression analysis was performed to determine if oral vancomycin-based therapy is associated with an increased risk of infection with gram-negative organisms after adjustment for other factors. Results Eighty-one patients were excluded because of recurrent episodes of CDI within the same year or missing information. 238 patients were included in the final analysis. 48 (20.2%) patients had positive culture for gram-negative organisms after onset of CDI. Urine was the most common source for gram-negative organisms (39/48, 81.3%) followed by blood (8/48,16.7%). The most common isolated gram-negative organisms were Escherichia coli (18/48, 37.5%) and Klebsiella pneumonia (9/48, 18.8%). The most common CDI treatment regimens were metronidazole monotherapy (137/238, 57.6%), vancomycin monotherapy (13/238, 5.5%), and combination therapy (88/238, 37.0%). Among patients who were treated with metronidazole monotherapy, vancomycin monotherapy, and combination therapy, 30(30/137, 21.9%), 3 (3/13,23.1%), and 15 (15/88, 17.1%) had positive culture for gram-negative organisms, respectively (P= 0.6). Ninety-seven (97/238,40.8%) patients had severe CDI, 40 (40/97, 41.2%) were treated with metronidazole monotherapy, 5(5/97, 5.2%) with vancomycin monotherapy, and 52 (52/97, 53.6%) with combination therapy. 26 (26/141,18.4%) and 22 (22/97, 22.7%) had positive culture for gram-negative organisms among patients with non-severe and severe CDI, receptively (P= 0.7). In the multivariate analysis, neither type of CDI treatment regimen (P=0.2, 95% CI 0.30–1.31) nor CDI severity (P=0.4, 95% CI 0.67–2.69) was associated an increased risk of infection with gram-negative organisms after CDI onset. Conclusions Contrary to the reported literature, we did not find that oral vancomycin-based CDI treatment was associated with increased risk of infection with gram-negative organisms. Funding Agencies None

Clostridioides difficile Infections in Adult and Pediatric Intestinal and Multivisceral Transplant Patients

Background Solid organ transplant (SOT) recipients are at increased risk of Clostridioides difficile infection (CDI). Studies addressing the epidemiology of CDI in intestinal and multivisceral transplant are limited. Since 2013, our center greatly expanded its intestinal and multivisceral transplant program, providing the consummate opportunity to examine CDI in this vulnerable population. Methods We conducted a retrospective study of all intestinal and multivisceral transplant recipients between 2009 and 2018. Results We identified 86 patients who underwent a total of 94 transplants. There were 60 isolated intestinal transplants (64%), 21 intestine/pancreas/liver (22%), 10 intestine/pancreas (11%), 2 intestine/pancreas/liver/kidney (2%), and 1 intestine/kidney transplant (1%). All but 3 patients received perioperative metronidazole. Four patients (5%) had CDI before transplant, but none experienced recurrence in the first 6 months posttransplant. Five patients suffered 7 mild-moderate episodes of early CDI (attack rate, 5.9%). Three patients (60%) with early CDI developed rejection, similar to the observed incidence (70%) in patients without CDI. Two patients with early CDI developed recurrent infection; both of these patients underwent intestinal retransplant. Overall, 1-year mortality was similar (20% among patients with early CDI vs. 23% among those without early CDI). Conclusions For certain solid organ transplant recipients, an association between CDI and allograft loss, rejection, and mortality has been shown. Although limited by sample size, we observed that early CDI was not associated with those outcomes in the present investigation. Multicenter studies are merited to explore risk factors for CDI and associations with transplant-related outcomes in intestinal and multivisceral transplant recipients.

Faecal microbiota transplantation in the treatment of Clostridioides difficile infection

Faecal microbiota transplantation (FMT) represents a unique procedure targeted to restoring the natural diversity of the gastrointestinal microbiome and prevent recurrence of a key nosocomial disease, namely, Clostridioides difficile infection (CDI). The aim of the present study was assessing the success rate and clinical efficacy of FMT at a clinic that introduced this procedure in Czechia in 2010 and still leads in the number of transplantations performed to date. Patients enrolled in the study received primary targeted antibiotic therapy, and after the CDI episode treatment, FMT administered as a secondary prophylaxis. After the procedure, patients were followed up. The treatment was defined as successful if colitis did not recur within 8 weeks. Logistic regression analysis was used for determining the odds ratios for the individual factor variants (patient age and sex, number of previous recurrences, severity of the treated CDI episodes, presence of chronic comorbidities, performance status, initial antibiotic treatment, mode of faecal-transplant application and use of fresh or frozen stool). In the 4-year interval involved (2015–2018), 172 patients were treated using faecal microbiota transplantation. The overall success rate was 76%. Subgroup analysis identified higher age, higher Charlson Comorbidity Index reflecting the presence and severity of long-term comorbidities and higher Eastern Cooperative Oncology Group (ECOG) performance scores as risk factors for treatment failure. In the period monitored, two serious adverse events were observed: Both were rectal-wall perforations occurring during the application of enemas of stool suspension. There was no lethality.

Recommendations and guidelines for the treatment of Clostridioides difficile infection in Taiwan.

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided.

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis

Aims: This study aimed to evaluate all-cause economic outcomes, healthcare resource utilization (HRU), and costs in patients with Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) using commercial claims from a large database representing various healthcare settings.Materials and methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus database was conducted for patients aged 18–64 years with CDI episodes requiring inpatient stay with CDI diagnosis code or an outpatient medical claim for CDI plus a CDI treatment. Index CDI episodes occurred between 1 January 2010 and 30 June 2017, including only those where patients were observable 6 months before and 12 months after the index episode. Each CDI episode was followed by a 14-d claim-free period. rCDI was defined as another CDI episode within an 8-week window following the claim-free period. HRU, all-cause direct medical costs and time to rCDI were calculated over 12 months and stratified by number of rCDI episodes.Results: A total of 46,571 patients with index CDI were included. Mean time from one CDI episode to the next was approximately 1 month. In the 12-month follow-up period, those with no recurrence had 1.4 inpatient visits per person and those with 3 or more recurrences had 5.8. Most patients with 3 or more recurrences had 2 or more hospital admissions. The mean annual, total all-cause direct medical costs per patient were $71,980 for those with no recurrence and $207,733 for those with 3 or more recurrences.Limitations: The study included individuals 18–64 years only. A stringent definition of rCDI was used, which may have underestimated the incidence of rCDI.Conclusions: CDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. Timing of recurrences can be predictable, providing a window of opportunity for interventions. Prevention of multiple rCDI appears essential to reduce healthcare costs.

Validation of the SHEA/IDSA severity criteria to predict poor outcomes among inpatients and outpatients with Clostridioides difficile infection

To determine whether the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) severity criteria adequately predicts poor outcomes. Retrospective validation study. Patients with CDI in the Veterans’ Affairs Health System from January 1, 2006, to December 31, 2016. For the 2010 criteria, patients with leukocytosis or a serum creatinine (SCr) value ≥1.5 times the baseline were classified as severe. For the 2018 criteria, patients with leukocytosis or a SCr value ≥1.5 mg/dL were classified as severe. Poor outcomes were defined as hospital or intensive care admission within 7 days of diagnosis, colectomy within 14 days, or 30-day all-cause mortality; they were modeled as a function of the 2010 and 2018 criteria separately using logistic regression. We analyzed data from 86,112 episodes of CDI. Severity was unclassifiable in a large proportion of episodes diagnosed in subacute care (2010, 58.8%; 2018, 49.2%). Sensitivity ranged from 0.48 for subacute care using 2010 criteria to 0.73 for acute care using 2018 criteria. Areas under the curve were poor and similar (0.60 for subacute care and 0.57 for acute care) for both versions, but negative predictive values were >0.80. Model performances across care settings and criteria versions were generally poor but had reasonably high negative predictive value. Many patients in the subacute-care setting, an increasing fraction of CDI cases, could not be classified. More work is needed to develop criteria to identify patients at risk of poor outcomes.

Outcome of Clostridioides difficile infections treated in a Swiss tertiary care hospital: an observational study.

Clostridioides difficile infection (CDI) is associated with high morbidity, recurrence rates and mortality. We assessed the local epidemiology, treatment outcomes and risk factors for recurrence and mortality. This was a retrospective study of all adult CDI episodes treated in our tertiary care hospital between 2014 and 2016. Patients were followed up for 60 days, with recurrence and death as endpoints. Antibiotic treatment as well as epidemiological, clinical and laboratory parameters were studied using logistic regression analysis. Risk factors for recurrent CDI (age &gt;70 years, haematological malignancy, chronic kidney disease, severe infection, continued antibiotics other than for CDI, proton pump inhibitor / antacid use) and indicators of severe CDI (temperature &ge;38.5&deg;C, leucocytes &gt;15 &times; 109/l, creatinine increase &ge;1.5 &times; baseline, albumin &lt;25 g/l) were analysed. We considered episodes with &ge;2 indicators as severe. We identified 210 CDI episodes (66 severe) in 191 patients with a median age of 71 years (interquartile range 59&ndash;79). Hypervirulent ribotype 027/NAP1/BI accounted for four episodes (2%). Overall, 176, 30 and 4 patients, respectively, received a first, second and third treatment. Metronidazole was used in 94% of the first episodes and in 73% and 50% of the first and second recurrences, respectively. The recurrence rate after the first metronidazole treatment was 20%. Recurrence rates were higher when &ge;2 risk factors were present (25 vs 10%, p = 0.03). The 60-day mortality was 17% (4% attributable to CDI) and increased with the presence of &ge;2 indicators of severe CDI. The high 60-day mortality suggests that CDI is a strong indicator of frailty. Metronidazole was associated with low recurrence rates at minimal costs in patients with uncomplicated CDI, but had relevant shortcomings in patients with severe CDI and/or a high risk of recurrence, suggesting that these vulnerable patients might better be treated with oral vancomycin and fidaxomicin, according to the latest guidelines. &nbsp.