Clostridioides Difficile Infection Severity Research Articles

Impact of colon cancer on outcomes in hospitalized patients with Clostridioides difficile infection: a national inpatient analysis

Background and aim Clostridioides difficile infection (CDI) burdens hospitalized patients, particularly those with comorbidities. Colon cancer may worsen CDI severity and outcomes. We aimed to assess CDI outcomes in hospitalized colon cancer patients. Methods A retrospective analysis of 2016 to 2020 National Inpatient Survey data identified adults with CDI, categorized by the presence of colon cancer. Hospitalization characteristics, comorbidities, and outcomes were compared between groups. Primary outcomes included in-hospital mortality, length of stay, and total hospital charges. The secondary outcomes were CDI complications. Multivariate logistic regression analysis was performed, with P values ≤0.05 indicating statistical significance. Results Among 1,436,860 CDI patients, 14,085 had colon cancer. Patients with colon cancer had a longer length of stay (10.77 vs 9.98 days; P < 0.001). After adjustment for confounders, colon cancer patients exhibited higher odds of acute peritonitis (adjusted odds ratio [aOR] 2.37; P = 0.009), bowel perforation (aOR 5.49; P < 0.001), paralytic ileus (aOR 2.12; P = 0.003), and colectomy (aOR 36.99; P < 0.001), but lower risks of mortality, sepsis, septic shock, acute kidney injury, cardiac arrest, and mechanical ventilation (all P < 0.001). Conclusion Colon cancer significantly impacts CDI outcomes in hospitalized patients, highlighting the need for improved management strategies to reduce morbidity and mortality.

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

ObjectivesRecurrent Clostridioides difficile infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus. MethodsWe 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). ResultsA 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. ConclusionSecondary 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.

The Strain and the Clinical Outcome of Clostridioides difficile Infection: A Meta-analysis.

The association between bacterial strains and clinical outcomes in Clostridioides difficile infection (CDI) has yielded conflicting results across studies. We conducted a systematic review and meta-analyses to assess the impact of these strains. Five electronic databases were used to identify studies reporting CDI severity, complications, recurrence, or mortality according to strain type from inception to June 2022. Random effect meta-analyses were conducted to assess outcome proportions and risk ratios (RRs). A total of 93 studies were included: 44 reported recurrences, 50 reported severity or complications, and 55 reported deaths. Pooled proportions of complications were statistically comparable between NAP1/BI/R027 and R001, R078, and R106. Pooled attributable mortality was 4.8% with a gradation in patients infected with R014/20 (1.7%), R001 (3.8%), R078 (5.3%), and R027 (10.2%). Higher 30-day all-cause mortality was observed in patients infected with R001, R002, R027, and R106 (range, 20%-25%).NAP1/BI/R027 was associated with several unfavorable outcomes: recurrence 30 days after the end of treatment (pooled RR, 1.98; 95% CI, 1.02-3.84); admission to intensive care, colectomy, or CDI-associated death (1.88; 1.09-3.25); and 30-day attributable mortality (1.96; 1.23-3.13). The association between harboring the binary toxin gene and 30-day all-cause mortality did not reach significance (RR, 1.6 [0.9-2.9]; 7 studies). Numerous studies were excluded due to discrepancies in the definition of the outcomes and the lack of reporting of important covariates. NAP1/BI/R027, the most frequently reported and assessed strain, was associated with unfavorable outcomes. However, there were not sufficient data to reach significant conclusions on other strains.

Comparative Effectiveness of Fidaxomicin vs Vancomycin in Populations With Immunocompromising Conditions for the Treatment of Clostridioides difficile Infection: A Single-Center Study.

Clostridioides difficile infection (CDI) is a leading cause of morbidity in immunocompromised hosts with increased risk of complications and recurrences. In this study, we examined the clinical effectiveness of fidaxomicin vs vancomycin in treating CDI in this patient population. This single-center retrospective study evaluated patients with CDI between 2011 and 2021. The primary outcome was a composite of clinical failure, relapse at 30 days, or CDI-related death. A multivariable cause-specific Cox proportional hazards model was used to test the relationship between treatment and the composite outcome, adjusting for confounders and treating death from other causes as a competing risk. This study analyzed 238 patients who were immunocompromised and treated for CDI with oral fidaxomicin (n = 38) or vancomycin (n = 200). There were 42 composite outcomes: 4 (10.5%) in the fidaxomicin arm and 38 (19.0%) in the vancomycin arm. After adjustment for sex, number of antecedent antibiotics, CDI severity and type of immunosuppression, fidaxomicin use significantly decreased the risk of the composite outcome as compared with vancomycin (10.5% vs 19.0%; hazard ratio, 0.28; 95% CI, .08-.93). Furthermore, fidaxomicin was associated with 70% reduction in the combined risk of 30- and 90-day relapse following adjustment (hazard ratio, 0.27; 95% CI, .08-.91). The findings of this study suggest that the use of fidaxomicin for treatment of CDI reduces poor outcomes in patients who are immunocompromised.

Factors Associated With Fecal Microbiota Transplant Failure in the Treatment of Recurrent Clostridioides difficile Infection: A Single-Center Retrospective Study.

Background Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI.Studies to date of predictors of FMT failure have primarily included inpatients. In this study, we aimed to describe FMT failure rates within one year of FMT and evaluate factors associated with FMT failure. Methodology We conducted an exploratory retrospective study of consecutive patients who underwent outpatient FMT at a single tertiary care center in Western Massachusetts from December 2014 through September 2018.We collected patient data including demographics, CDI-related factors, and FMT-related factors. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. difficile toxin or polymerase chain reaction. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Results A total of 92 patients were included with a mean age of 64 years. CDI severity was mild or moderate in 73% and severe or fulminant in 27%. The most common FMT indication was recurrent CDI in 76% of patients. FMT failure occurred in 25 of 92 (27%) patients, with half occurring within 11 days. Factors associated with FMT failure were active malignancy (RR = 2.56), prior hospitalizations (RR = 2.42), and receipt of non-CDI antibiotics within six months of FMT (RR = 2.80). We did not observe strong associations for risk of FMT failure with age ≥65, sex, use of proton pump inhibitors or H2 receptor agonists, history of colectomy, immunosuppression, history of malignancy, diabetes, appendectomy, CDI severity, or probiotic use. Conclusions Active malignancy, prior CDI hospitalizations, and non-CDI antibiotics within six months before FMT were associated with FMT failure in the outpatient setting. Knowledge of the above factors may help inform shared decision-making with patients at risk for FMT failure.

A retrospective study investigating the management, risk factors, and outcomes of patients diagnosed with Clostridioides difficile infection

AbstractBackgroundThe rate of clostridioides difficile infection (CDI) in Australia has increased by more than 8% between 2016–2018. This can be attributed to multiple factors including an ageing population, widespread antibiotic and proton‐pump‐inhibitor usage.AimThe aim of this study was to investigate the management, risk factors and outcomes for CDI to identify strategies to reduce its incidence.MethodA single‐centre retrospective audit was completed using medical records for patients admitted to a 250‐bed regional Queensland hospital with CDI in 2020–2021. Data surrounding CDI management for each patient was analysed against the Therapeutic Guidelines. This study was approved by The Prince Charles Hospital Human Research Ethics Committee (Reference No: LNR/HREC/QPCH/81287).ResultsThere were 72 cases with CDI during the study timeframe. Recent antibiotic prescription, proton‐pump‐inhibitor (PPI) use and antibiotic allergy labels were common. Thirty‐five per cent of cases were treated appropriately. Eight per cent died, and nine per cent had relapsed CDI within 12 weeks of diagnosis. Common gaps found in the results included inappropriate selection of antibiotics based on the severity of disease and lack of documentation surrounding CDI cases left untreated.ConclusionThere are multiple opportunities for pharmacists to improve the care of patients with CDI which range from promoting guideline adherence, influencing prescriber antibiotic selection based on disease severity, prompting review of PPIs upon CDI diagnosis and prompting provider follow‐up of CDI laboratory results pending at the point of patient discharge. The results of this study have prompted antimicrobial stewardship service review of all CDI admissions at the study site and indicates the need for a larger multiple‐site study to raise awareness of CDI risk factors and severity criteria.

ANTIDEPRESSANT MEDICATIONS ARE ASSOCIATED WITH INCREASED RISK OF HOSPITAL-ACQUIRED CLOSTRIDIOIDES DIFFICILE INFECTION: A POPULATION-BASED STUDY.

•The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

Prevention and treatment of C. difficile in cancer patients.

We provide an update on the recent literature on Clostridioides difficile infection (CDI) in cancer patients. Distinguishing between colonization and infection remains challenging in cancer patients. Many patients with negative toxin analysis are still treated for CDI, and some meet criteria for severe cases. The incidence of CDI is high in cancer patients, especially those with haematological malignancies. Disruption of the gut microbiome due to antibiotic consumption, chemotherapy and radiotherapy is the primary factor contributing to CDI development. The severity of CDI in cancer patients is often unclear due to the absence of well-defined severity criteria. Certain microbiome species predominance and specific ribotypes have been associated with worse outcomes. Whole genome sequencing could be helpful for differentiating recurrence from reinfection and exploring potential nosocomial transmission. While certain new drugs such as fidaxomicin or bezlotoxumab show promise, the optimal treatment and prevention strategies for CDI in cancer patients remain uncertain. Faecal microbiota transplantation (FMT) holds potential for reducing CDI recurrence rates. Further studies are needed to provide robust recommendations for diagnosis, grading severity, and therapeutic management of CDI in cancer patients. Recurrences are particularly concerning due to subsequent exposition to CDI risk factors.

A Systematic Review and Meta-Analysis: A Prior Appendectomy Does Not Increase the Risk of Severe Clostridioides difficile Infection or Recurrence.

There is conflicting evidence regarding the association betweenaprior appendectomy and severity of Clostridioides difficile infection. The aim of this study was to perform a systematic review and meta-analysis to evaluate this association. Comprehensive review of multiple databases was performed up to May 2022. The primary outcome assessed was the rate of severe Clostridioides difficile infection in patients with a prior appendectomy compared to patients with an appendix. The secondary outcomes assessed were recurrence, mortality, and colectomy rates associated with Clostridioides difficile infection in patients with a prior appendectomy compared to patients with an appendix. Eight studies with 666 patients with a prior appendectomy and 3580 patients without an appendectomy were included. The odds ratio of severe Clostridioides difficile infection in patients who underwent prior appendectomy was 1.03 (95% CI 0.6-1.78, p = 0.92). The odds ratio of recurrence in patients who underwent prior appendectomy was 1.29 (95% CI 0.82-2.02, p = 0.28). The odds ratio of colectomy due to Clostridioides difficile infection in patients who underwent prior appendectomy was 2.16 (95% CI 1.27-3.67, p = 0.004). The odds ratio of mortality due to Clostridioides difficile infection in patients with a prior appendectomy was 0.92 (95% CI 0.62-1.37, p = 0.68). Patients with appendectomy are not at increased risk for developing severe Clostridioides difficile infection or recurrence. Further prospective studies are needed to establish these associations.

Clostridioides difficile PCR Tcdb Cycle Threshold predicts toxin EIA positivity but not severity of infection

BackgroundDiagnosis of Clostridioides difficile Infection (CDI) entails compatible clinical presentation and laboratory findings. We evaluated real-time polymerase chain reaction (qPCR) cycle threshold (CT) as a predictor for disease severity and TcdB enzyme immunoassay (EIA) results. MethodsInpatients or emergency department patients who tested positive for tcdB gene by PCR were evaluated. Patients’ stools underwent testing for GDH and TcdA/B by EIA. Medical health records were reviewed for demographic, clinical presentation, laboratory, treatment and outcome data. Severity of CDI was calculated using various severity score indexes. ResultsThe median CT of cases was 32.05 ± 5.45. The optimal cut-off for predicting toxin EIA positivity and severe CDI based on chart review was 32.6 and 29.8, respectively, with the area under the receiver operator characteristics curve (AUC) of 0.74 and 0.60 respectively. ConclusionCT value was an acceptable predictor for EIA toxin but less so for clinical severity. Our study potentially supports a diagnostic algorithm including CT value to reduce the number of EIA toxin assays performed.

Community-associated Clostridioides difficile infection in a general hospital from Argentina

Toxin-producing Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea. However, it is now recognized as a cause of diarrhea in the community. This single-center study aimed to determine the epidemiological origin of CDI cases between January 2014 and December 2019 and to compare demographic characteristics, comorbidities, risk factors, severity, and mortality of community CDI with healthcare facility-associated CDI. There were 52 CDI cases from the community (34.4%). Community patients were significantly younger (53 yo vs. 65 yo), less comorbid (Charlson Index 1.65 vs. 3.98), and less severe (only one case). The main risk factor was the use of antibiotics in the previous 90 days (65%). However, we did not find any known risk factor in 7 patients.

Community versus health care-associated Clostridioides difficile infection: A comparison between clinical characteristics and outcomes in hospitalized patients

Clostridioides difficile infection (CDI) can be divided according to its acquisition site, health care (HC) or community (CA) associated CDI. Studies showed severe disease, higher recurrence, and mortality among HC-CDI patients, while others reported the opposite. We aimed to compare the outcomes according to the CDI acquisition site. The study analyzed medical records and laboratory computerized system data to identify patients (≥18 years old) who were hospitalized with the first CDI from January 2013 to March 2021. Patients were divided into HC-CDI and CA-CDI groups. The primary outcome was 30-day mortality. Other outcomes: CDI severity, colectomy, intensive care unit (ICU) admission, length of hospitalization, 30 and 90-day recurrence, and 90 days all-cause mortality. Of 867 patients, 375 were defined as CA-CDI and 492 as HC-CDI. CA-CDI patients had more underlying malignancy (26% vs 21% P=.04) and inflammatory bowel disease (7% vs 1%, P<.001). The 30 days mortality was similar (10% CA-CDI and 12% HC-CDI, P=.5), and the acquisition site was not found to be a risk factor. There was no difference in severity nor in complications, but the recurrence rate was higher among those with CA-CDI (4% vs 2%, P=.055). There were no differences between the CA-CDI and HC-CDI groups regarding rates, in-hospital complications, short-term mortality,and 90-day recurrence rates. However, the CA-CDI patients had a higher recurrence rate at 30 days.

Frailty level at discharge predicts mortality in older patients with Clostridioides difficile more accurately than age or disease severity

Key summary pointsAimTo calculate mortality rates in older patients with Clostridioides difficile infection (CDI) and compare multidimensional frailty level, CDI severity and age as predictors of mortality.FindingsOlder patients with their first CDI had a high 90-day mortality of 28%. Multidimensional frailty assessment at discharge outperformed CDI severity and age in predicting 90-day mortality among older patients with CDI.MessageCompared with age and CDI severity, the multidimensional frailty assessment is the best predictor of 90-day mortality in older patients with CDI.

Fecal microbiota transplantation as potential first-line treatment for patients with Clostridioides difficile infection and prior appendectomy.

Clostridioides difficile infection (CDI) is a global health problem. The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures, but there are still contradictions. In a retrospective study entitled "Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes" published in World J Gastrointest Surg 2021, the author found that prior appendectomy affects the severity of CDI. Appendectomy may be a risk factor for increasing the severity of CDI. Therefore, it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.

Fecal Microbiota Transplantation for Fulminant Clostridioides Difficile Infection: A Combined Medical and Surgical Case Series.

Urgent abdominal colectomy is indicated for patients with fulminant Clostridioides difficile infection (CDI) when other medical therapies fail, yet mortality remains high. Fecal microbiota transplant is a less invasive alternative approach for patients with fulminant CDI. We report the 30-day complications of patients with fulminant CDI who underwent either abdominal colectomy, fecal microbiota transplantation (FMT), or FMT followed by abdominal colectomy (FMT-CO). Methods: We performed a single-center, retrospective case review of combined medical and surgical patients with CDI at a large academic medical center between 2008 and 2016. Cohorts were identified as patients with fulminant CDI who underwent total abdominal colectomy alone (CO), FMT alone (FMT), or FMT-CO. We analyzed patient demographics, history, comorbidities, clinical and laboratory variables, CDI severity scores, and mortality outcomes at 30 days. Results: We identified 5,150 patients with CDI at our center during the review period; 16 patients met the criteria for fulminant CDI and were included in this study, with four patients in the CO cohort, eight patients in the FMT cohort, and four patients in the FMT-CO cohort. Demographics and CDI severity scores were similar for all three groups, although the selected comorbidity profiles differed significantly among the three cohorts. The 30-day mortality rates for patients in the CO, FMT, and FMT-CO groups were 25%, 12.5%, and 25%, respectively. Conclusions: FMT is an alternative or adjunctive therapy to colectomy for patients with fulminant CDI that is not associated with increased mortality. Implementation of FMT protocols in clinical practice would be dependent on the availability of qualified transplant material and successful early identification of patients likely to benefit from FMT.

Clinical Usefulness of the "MN Criteria" - the Clostridioides difficile Infection Severity Scoring System - in the Japanese Setting.

Objective The severity of Clostridioides difficile infection (CDI) is an important prognostic factor. The "MN criteria," proposed in Japan in 2017, attempted to remedy the shortfalls in the reported guidelines proposed globally to determine CDI severity. We therefore assessed the accuracy of the MN criteria and validated the important factors associated with predicting CDI severity. Methods Sixty-six CDI cases were investigated retrospectively at a Japanese University Hospital from January 2015 to December 2018. The fulminant cases were screened out, and the non-fulminant cases were classified according to their severity stages using the nine variables included in the MN criteria. Clinical events, such as death within 28 days, colectomy, and admission to the intensive-care unit, were evaluated. First, the sensitivity and specificity of the MN criteria for predicting clinical events were determined. The relationships between clinical events and the explanatory variables were then evaluated through univariate and multivariate analyses. Results The screening of the fulminant cases and classification of the non-fulminant cases into mild/moderate and severe/super severe cases resulted in a sensitivity of 1.00 and a specificity of 0.89. Univariate and multivariate analyses revealed a significant association of the serum albumin level (Alb) as well as white blood cell count (WBC) with clinical events. Conclusion The findings provide evidence supporting the accuracy of the MN criteria in predicting CDI severity and show that the Alb and WBC are important variables in predicting CDI severity.

Risk Factors Associated with Severe Clostridioides difficile Infection in Patients with Cancer.

Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer. This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C.difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels. On univariate analysis, factors associated with severe CDI included the presence of toxinA/B in stools (odds ratio [OR] 2.14 [1.05-4.36] p = 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09-6.50] p = 0.03). Although alpha and beta diversity was similar between disease severity groups and toxinA/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseri were associated with protection from severe CDI (p < 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure. Use of metronidazole for non-CDI indications within 90days prior to diagnosis and presence of toxinA/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.

Correlation of Clinical Severity With Stool Microbiome Changes in Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is the world-leading cause of infectious nosocomial diarrhea and pseudomembranous colitis. Antibiotics are the first line of treatment against CDI despite the high likelihood of antibiotic failure and/or recurrence. More data are needed to correlate clinical variables with 16S rRNA microbiome profiles in CDI-infected patients. To determine the relationship(s) between a patient's clinical factors and the stool bacteriome of CDI-positive patients and CDI-negative patients with diarrheal symptoms. This study used stool samples and clinical data from 358 patients with nosocomial diarrhea, who were divided by their CDI diagnosis (CDI-negative: n = 180; CDI-positive; n = 178). The stool bacteriome was profiled by amplicon deep sequencing of the 16S rRNA gene, followed by correlating clinical data. The stool bacteriome was significantly different by severity assessment regardless of CDI status. Phyla and species varied significantly by CDI diagnosis. Severity, defined as a serum white blood cell count greater than 15 cells/μL and/or a creatinine level greater than 1.5 mg/dL, correlated significantly with dysbiosis of the stool bacteriome profile of CDI-positive patients compared to CDI-negative patients. Serum white blood cell count was significantly higher in patients with bacterial dysbiosis, and high levels of creatinine were associated with low bacteriome diversity. Clinical severity of CDI influences the stool microbiome of infected patients. To date, this study has the largest data set comparing 16S rRNA microbiome profiles and clinical variables between CDI-infected and noninfected individuals.

S223 Factors Related to Fecal Microbiota Transplant Failure in the Treatment of Recurrent C. difficile - A Single Center Retrospective Cohort Study

Introduction: Fecal Microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridioides difficile infection (CDI) with reported success rates of 80-90%. There are limited data on factors contributing FMT failure, particularly in the outpatient setting. Our objective was to describe FMT failure rates within one year and to evaluate factors associated with FMT failure. Methods: We conducted a retrospective cohort study of consecutive patients who had outpatient FMT at Baystate Medical Center, Springfield, MA from 12/14 through 9/18. We collected patient data including demographics, CDI related factors, comorbid conditions, medications and FMT route. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. diff toxin or PCR. IRB approval was obtained. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Due to low power, we present possible associations with p-values < 0.2. Results: 92 patients were included with a mean age of 64y. CDI severity (per IDSA guidelines) was mild/moderate in 73% and severe or fulminant in 27%. 69% of patients had been previously hospitalized for CDI and the most common FMT indication was recurrent CDI in 76%. FMT failure occurred in 25 of 92 (27%) of which half occurred within 21 days. Factors associated with FMT failure were immunosuppression (RR=2.90); current or previous malignancy (RR=2.50); prior hospitalizations (RR=2.42); and receipt of non-CDI antibiotics within 6 months of FMT (RR=2.80). None of the following factors were associated with risk of FMT failure: age, indication, CDI severity, history of colectomy, diabetes, prior radiation, history of appendectomy, probiotics prior to FMT, H2 antagonists or PPIs, ICU admission, inflammatory bowel disease, or route of FMT delivery (oral, NGT, colonoscopy). (Table) Conclusion: We have identified four factors associated with FMT failure for outpatients with recurrent CDI: immunosuppression, current or previous malignancy, prior CDI hospitalizations and non-CDI antibiotics within 6 months prior to FMT. Knowledge of the above factors may help inform treatment options for patients with recurrent or refractory CDI. Table 1. - Univariable analysis of associations between factors associated with FMT failure within one year Overall FMT FailureNo FMT FailureYes p- value Relative Risk N=92 N=67 N=25 (95% CI) Age at transplant (yrs) 63.9 65.1 60.7 0.319 0.92 (0.77 to 1.10) Male n=20 (21.7%) Female n=72 (78.3%) FMT Indication Recurrent CDI 70 (76.1%) 54 (77.1%) 16 (22.9%) 0.062 n/a Severe CDI 3 (3.3%) 3 (100.0%) 0 (0.0%) Fulminant Colitis 2 (2.2%) 2 (100.0%) 0 (0.0%) Recurrent and Severe CDI 17 (18.5%) 8 (47.1%) 9 (52.9%) CDI Severity Mild/Moderate 67 (72.8%) 51 (76.1%) 16 (23.9%) 0.415 Referent Severe 15 (16.3%) 10 (66.7%) 5 (33.3%) 1.40 (0.61 to 3.21) Fulminant Colitis 10 (10.9%) 6 (60.0%) 4 (40.0%) 1.67 (0.70 to 4.00) Prior Hospitalization Due to C. Diff No 29 (31.5%) 25 (86.2%) 4 (13.8%) 0.076 Referent Yes 63 (68.5%) 42 (66.7%) 21 (33.3%) 2.42 (0.91 to 6.40) Immunosuppression No 57 (62.0%) 48 (84.2%) 9 (15.8%) 0.003 Referent Yes 35 (38.0%) 19 (54.3%) 16 (45.7%) 2.90 (1.44 to 5.83) Current or Previous Malignancy No 70 (76.1%) 56 (80.0%) 14 (20.0%) Referent Yes 22 (23.9%) 11 (50.0%) 11 (50.0%) 0.012 2.50 (1.33 to 4.68) Antibiotics (6 mos. prior to cdiff; not treating c.diff.) No 32 (34.8%) 28 (87.5%) 4 (12.5%) 0.027 Referent Yes 60 (65.2%) 39 (65.0%) 21 (35.0%) 2.80 (1.05 to 7.46)

Systematic review of guidelines for the diagnosis and treatment of Clostridioides difficile infection

ObjectiveTo systematically assess the current related methodological quality of guidelines for the diagnosis and treatment of Clostridioides difficile infection (CDI), revealing the heterogeneity and reasons for guideline recommendations for the diagnosis and treatment of CDI.MethodsWe searched electronic databases systematically between 2017 and 2021 to find the latest guidelines for the diagnosis and treatment of CDI. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used for quality assessment of the included guidelines. The main recommendations for the diagnosis and treatment of CDI in the guidelines were extracted and evaluated for consistency, and the level of evidence supporting these recommendations was further extracted and analysed.ResultsFourteen guidelines for the diagnosis and treatment of CDI were finally included in this study. There were four guidelines, BSG and HIS, ASCRS, IDSA AND SHEA, and NICE, with an overall score of more than 60%, which is worthy of clinical recommendation. Further analysis of the consistency of the main recommendations for the diagnosis and treatment of CDI in the guidelines showed that the recommendations differed among guidelines. There are no unified classification criteria for the severity of CDI in current studies; some recommendations for the diagnosis and treatment of CDI do not provide evidence to support the recommendations, most recommendations cite low levels of evidence, and there is a lack of high-quality research evidence.ConclusionThe quality of guidelines for the diagnosis and treatment of CDI is uneven. Recommendations on the diagnosis and treatment of CDI have also varied in the guidelines for the past 5 years. Improvements of the aforementioned factors associated with causing heterogeneity would be a rational approach by guideline developers to further update guidelines for the diagnosis and treatment of CDI.