Complicated Clostridium Difficile Infection Research Articles

The prevalence, risk factors, and complications of Clostridium difficile infection in a tertiary care center, western region, Saudi Arabia

BackgroundClostridium difficile is an anaerobic gram-positive spore-forming bacillus that is most commonly associated with nosocomial diarrhea. This study aimed to analyze the prevalence and risk factors of Clostridium difficile infection (CDI) at a tertiary health care center, Western region, Saudi Arabia. We also aimed to examine the duration of exposure to each risk factor prior CDI development, and to categorize CDI as severe and non-severe depending on the white blood cell (WBC) count. Various complications of the infection were also analyzed. MethodsWe performed a retrospective chart review of all patients who had a positive nucleic acid amplification test (NAAT) for Clostridium difficile toxin genes between October 2018 and October 2020. ResultsThe prevalence of CDI among the included patients was 9.1% (237 of 2611 patients). The mean age (standard deviation) was 56.86 (21) years, and the infection was more prevalent among men (52.74%) than among women (47.26%). The most common risk factor associated with CDI was recent antibiotic use (74.68%), followed by recent acid suppressant use (67.50%), malignancy (46%), and previous gastrointestinal surgery (6.30%). The CDI recurrence rate was 13.90%. Piperacillin-tazobactam was the most frequently used broad-spectrum antibiotic, and was used in 38.8% of the patients, followed by meropenem. The most common malignancy type was lymphoma (22.94%, n = 25), followed by leukemia (n = 23). The most common type of surgery was subtotal colectomy (n = 6). Three patients underwent transverse colon resection, and two underwent ileocecal resection. Hypotension was the most frequently recorded complication (28.40%) in the study population. ConclusionThe prevalence rate of CDI among the study patients during the two-year study from October 2018 to October 2020 was 9.1%. Appropriate use of antibiotic and acid suppressants, and contact isolation measures can help in decreasing the number of CDI cases.

S1797 Successful Fecal Microbiota Transplant Delivered by Foley Catheter Through a Loop Ileostomy in a Patient With Severe Complicated Clostridium difficile Infection

S1797 Successful Fecal Microbiota Transplant Delivered by Foley Catheter Through a Loop Ileostomy in a Patient With Severe Complicated Clostridium difficile Infection

The Impact of Appendectomy in Clostridium difficile Infection and Length of Hospital Stay

IntroductionWe aim to investigate Clostridium difficile infection (CDI) recurrence, severity, complications, and length of hospital stay in patients with and without prior history of appendectomy who were admitted to the hospital with CDI.MethodWe analyzed retrospective data for 862 patients, 18 years and older, with C. difficile inpatients diagnosed between January 1, 2017 and December 31, 2018 and sorted into two groups, with or without prior appendicectomy, to look for outcomes such as recurrence, hospital stay, complications, and related death in each group and use statistical analysis for comparison.ResultThere were 862 patients admitted with CDI, of which 122 (14.2%) had a prior history of appendectomy and 740 (85.8%) did not. Patients with an appendectomy prior were older (median age of 75 vs. 69, p = 0.0033) and had a higher proportion of females (68.9% vs. 53.6%, p = 0.0017).C. difficile recurrence in prior appendicectomy group vs. no appendectomy group was 12.3% and 9.3%, respectively, but no statistical difference was noted (p = 0.28). Also, there was no statistical difference in complications like ileus, colectomy, and mortality related to CDI in both groups. However, patients with appendectomies had significantly shorter hospital stays during C. difficile admission compared to patients without appendectomies (median of six days vs. seven days, p = 0.0014).ConclusionOur study shows that there is no statistical difference in the recurrence, severity, and complications of CDI in the presence or absence of the appendix but remarkably noted that people with prior appendicectomy had a shorter hospital stay.

Severe complicated Clostridium difficile infection: A case report

Severe complicated Clostridium difficile infection: A case report

2413. Assessment of compliance with Clostridioides difficile prophylaxis guideline and its efficacy on secondary prophylaxis and reducing hospital-onset Clostridioides difficile infections.

BackgroundOne of the complications of Clostridium difficile infection (CDI) is the risk of recurrence, particularly in high-risk patients who are exposed to broad-spectrum antibiotics (BSA). Antimicrobial stewardship program at our institution developed Clostridium difficile prophylaxis (CDP) guidelines. Purpose of this study was to evaluate the compliance to this guideline and evaluate the efficacy of it preventing recurrent CDI.MethodsThis was an IRB approved retrospective study performed at a 607-bed community health system between 2014–2016. Patients were included if they were ≥18 years old and admitted for > 24 hours on BSA with history of CDI in last 6 months. CDI prophylaxis was provided with oral vancomycin 125 PO BID. Patients were excluded if they had active CDI receiving metronidazole or treatment doses of oral vancomycin. Patients were compared in two cohorts: Study group which was patients in CDP group which were matched to control group. The primary objective of the study was to evaluate the compliance of CDP guidelines and incidence of hospital-onset CDI (HO-CDI) between CDP group and control group. The secondary objective focused on all-cause inpatient mortality and 30-day readmission between two groups.ResultsThere were total of 72 patients reviewed and 47 patients met the inclusion criteria for CDP group which were matched with control group. Most common type of infection and BSA were pnuemonia (26%) and broad-spectrum cephalosporins (31%), respectively. CDP guidelines compliance was measured at 65%. The incidence of HO-CDI/10000 patient-days during the admission was lower in CDP group compared with control group (2.02 vs 5.4 per 10,000 PD, P = 0.03). No differences were seen in all-cause inpatient mortality and 30-day readmission between two groups. Forty-five percent of patients suffered from CDI < 3 months prior to admission. The most common dose of oral vancomycin was 125 mg PO BID.ConclusionPatients in CDP group had a lower incidence of developing HO-CDI compared with control group. Overall compliance with CDP guidelines was higher than expected. No difference was seen in all-cause inpatient mortality and 30-day readmission between two groups. Oral vancomycin 125 mg PO BID shows promising results as a secondary prophylaxis in patients receiving BSA.Disclosures All authors: No reported disclosures.

756 Novel Risk Factors and Outcomes in Inflammatory Bowel Disease Patients With Clostridium difficile Infection

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridium difficile infection (CDI). CDI in IBD is associated with increased in-hospital mortality, IBD treatment failure, re-hospitalization and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors (BMI, statin use, opioid use, and antidepressant use) on the risk and outcomes of CDI in patients with IBD. METHODS: CDI disease severity and other clinical outcomes, including colon surgery, CDI recurrence, CDI-related hospitalization, IBD exacerbations, and mortality were abstracted using the electronic medical record. Additionally, variables including BMI, statin use, opioid use, and antidepressant use at the time of CDI were abstracted from records for patients with IBD and CDI from 2008 and 2013. Statistical analysis comprised of descriptive statistics and univariate and multivariate logistic regression analyses. RESULTS: There were 137 patients with IBD and CDI included in this study: 70 with ulcerative colitis (51%), 63 with Crohn's disease (46%), and 4 with indeterminate colitis (3%). The median age was 46 years, and 55% were female. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe complicated CDI, compared to 22% of patients in the underweight/normal BMI (OR, 2.85, P = 0.02) and 19% in the obese category (OR, 3.95, P = 0.04). Statin use was associated with severe or severe complicated CDI when controlling for age and BMI (OR, 5.66, P = 0.01). On multivariate analysis controlling for age and CDI severity, there was no association between statin use and post-CDI IBD exacerbations. Opioid and antidepressant use were not associated with CDI disease severity or IBD exacerbations. BMI category, statin use, opioid use, and antidepressant use were not associated with colon surgery, CDI recurrence, CDI-related hospitalizations, or mortality at 1 year. CONCLUSION: An overweight BMI and statin use were associated with severe or severe complicated CDI. There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Further studies are needed to better understand how these results could impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of CDI.

Intensity of Therapy for Malignancy and Risk for Recurrent and Complicated Clostridium difficile Infection in Children.

Clostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.

Using Machine Learning and the Electronic Health Record to Predict Complicated Clostridium difficile Infection.

Background Clostridium (Clostridioides) difficile infection (CDI) is a health care–associated infection that can lead to serious complications. Potential complications include intensive care unit (ICU) admission, development of toxic megacolon, need for colectomy, and death. However, identifying the patients most likely to develop complicated CDI is challenging. To this end, we explored the utility of a machine learning (ML) approach for patient risk stratification for complications using electronic health record (EHR) data.MethodsWe considered adult patients diagnosed with CDI between October 2010 and January 2013 at the University of Michigan hospitals. Cases were labeled complicated if the infection resulted in ICU admission, colectomy, or 30-day mortality. Leveraging EHR data, we trained a model to predict subsequent complications on each of the 3 days after diagnosis. We compared our EHR-based model to one based on a small set of manually curated features. We evaluated model performance using a held-out data set in terms of the area under the receiver operating characteristic curve (AUROC).ResultsOf 1118 cases of CDI, 8% became complicated. On the day of diagnosis, the model achieved an AUROC of 0.69 (95% confidence interval [CI], 0.55–0.83). Using data extracted 2 days after CDI diagnosis, performance increased (AUROC, 0.90; 95% CI, 0.83–0.95), outperforming a model based on a curated set of features (AUROC, 0.84; 95% CI, 0.75–0.91).ConclusionsUsing EHR data, we can accurately stratify CDI cases according to their risk of developing complications. Such an approach could be used to guide future clinical studies investigating interventions that could prevent or mitigate complicated CDI.

P072 NOVEL RISK FACTORS AND OUTCOMES IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH CLOSTRIDIUM DIFFICILE INFECTION

Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridium difficile infection (CDI). CDI in IBD is associated with increased in-hospital mortality, IBD treatment failure, re-hospitalization and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited; however, a recent study demonstrated that corticosteroid escalation for IBD during CDI was a positive predictor of colon surgery within 1 year. We evaluated four potentially modifiable novel risk factors (BMI, statin use, opioid use, and antidepressant use) on the risk and outcomes of CDI in patients with IBD. CDI disease severity and other clinical outcomes, including colon surgery, CDI recurrence, CDI-related hospitalization, IBD exacerbations, and mortality were abstracted using the electronic medical record. Additionally, variables including BMI, statin use, opioid use, and antidepressant use at the time of CDI were abstracted from records for patients with IBD and CDI from 2008 and 2013. Statistical analysis comprised of descriptive statistics and univariate and multivariate logistic regression analyses. There were 137 patients with IBD and CDI included in this study: 70 with ulcerative colitis (51%), 63 with Crohn’s disease (46%), and 4 with indeterminate colitis (3%). The median age was 46 years, and 55% were female. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe complicated CDI, compared to 22% of patients in the underweight/normal BMI (OR, 2.85, p=0.02) and 19% in the obese category (OR, 3.95, p=0.04). Statin use was associated with severe or severe complicated CDI when controlling for age and BMI (OR, 5.66, p=0.01). On multivariate analysis controlling for age and CDI severity, there was no association between statin use and post-CDI IBD exacerbations. Opioid and antidepressant use were not associated with CDI disease severity or IBD exacerbations. BMI category, statin use, opioid use, and antidepressant use were not associated with colon surgery, CDI recurrence, CDI-related hospitalizations, or mortality at 1 year. An overweight BMI and statin use were associated with severe or severe complicated CDI. There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Further studies are needed to better understand how these results could impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of CDI.

2,4-Disubstituted 5-Nitroimidazoles Potent against Clostridium difficile.

Metronidazole is one of the first-line treatments for non-severe Clostridium difficile infections (CDI). However, resistance limits its use in cases of severe and complicated CDI. Structure-activity relationships previously described for the 5-nitroimidazole series have shown that functionalization at the 2- and 4-positions can impart better activity against parasites and anaerobic bacteria than metronidazole. Herein we report the synthesis of new 2,4-disubstituted 5-nitroimidazole compounds that show potent antibacterial activity against C. difficile. We used a vicarious nucleophilic substitution of hydrogen (VNS) reaction to introduce a phenylmethylsulfone at the 4-position and a unimolecular radical nucleophilic substitution (SRN 1) reaction to introduce an ethylenic function at the 2-position of the 5-nitroimidazole scaffold.

Comparison of Outcomes Between Total Abdominal and Partial Colectomy for the Management of Severe, Complicated Clostridium Difficile Infection

Patients with severe, complicated Clostridium difficile infection (CDI) may ultimately require a colectomy. Although associated with high morbidity and mortality, a total colectomy has been the mainstay of surgical treatment. However, small studies have suggested partial colectomy may provide equivalent outcomes. We compared the outcomes of partial and total colectomy for CDI in a nationwide database. We performed a retrospective study using the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). Patients with a primary diagnosis of Clostridium difficile colitis from 2007 to 2015, who underwent a total abdominal or partial colectomy, were analyzed. Postoperative mortality rate, complications, and length of stay were evaluated. Logistic regression controlling for patient and clinical factors evaluated the impact of type of operation performed. There were 733 colectomies for CDI, of which 151 (20.6%) were partial colectomies. Patients with a partial colectomy had a slightly higher 30-day mortality rate (37.1%) compared with total abdominal colectomy patients (34.7%, p= 0.58). However, logistic regression controlling for patient factors demonstrated no statistically significant difference for partial colectomy in 30-day mortality (odds ratio [OR] 1.21, 95% CI 0.76 to 1.96) or complication rate (OR 0.92, 95% CI 0.51 to 1.62) compared with total colectomy. There was no difference in days to surgery (4.6 partial vs 5.0 total, p= 0.70). Total abdominal colectomy trended toward a longer postoperative stay (18.0 vs 15.1 days for partial, p= 0.08). In a national database, a significant percentage of operations for CDI are partial colectomies. There were no significant differences found in mortality or complications between partial and total colectomy for severe complicated CDI.

Taming the Beast: The Safety and Efficacy of Fecal Microbiota Transplantation in Severe and Complicated Clostridium difficile Infection

Taming the Beast: The Safety and Efficacy of Fecal Microbiota Transplantation in Severe and Complicated Clostridium difficile Infection

Charlson Comorbidity Index (CCI): An Independent Predictor of Outcomes in Clostridium difficile Infection (CDI)

Introduction: Clostridium difficile infection (CDI) has emerged as a major healthcare-associated infection. The incidence of this infection, related hospitalizations and mortality rates seem to be increasing every year. Certain established risk factors and comorbid conditions are thought to have a prognostic impact on the outcomes of patients with CDI. We studied the significance of Charlson Comorbidity Index (CCI) as an independent tool to predict the outcomes in these patients. Methods: We conducted a retrospective observational study at our institution between July 1st, 2014 and June 30th, 2017. We included all individual admitted to our institution whose stool tested positive for Glutamate Dehydrogenase (GDH) and was confirmed by Nucleic Acid Amplification Test (NAAT). Demographic, clinical, laboratory and pharmacological data was abstracted from our EHR (Electronic Health Records). The data was analyzed using standard statistical methods and JMP14 software. We divided patients into two groups based on in-hospital mortality. Results: In our study we included a total of 314 individual who met the inclusion criteria. We observed no difference in the outcomes of the patients based on their gender. The mean age of patients who died was 64.5 years while the mean age of those who survived was 57.5 (p value = 0.016). Furthermore, the mean CCI of the patients who died was 7.37 while of those who survived was 4.4 (p value = 0.0001 ) (Table 1).We also compared the Charlson Comorbidity Index(CCI) in mild-moderate, severe and complicated CDI which corresponded with disease severity (6.20, 5.70 and 4.06 respectively (p value = Conclusion: Current CDI outcome prediction models are based on disease severity. Our study sheds light into a new area of CCI and mortality in individuals with CDI. We observed known risk factors like age, severity of disease correlated with mortality. However, we noticed higher CCI score in relation to mortality during hospitalization. As CCI is a quick and readily available tool, we hope this finding will help healthcare professionals to predict outcomes in patients with CDI to manage them more efficiently for better outcomes.2743 Figure 1 No Caption available.

Early results of fecal microbial transplantation protocol implementation at a community-based university hospital

Introduction:Clostridium difficile (CD) is a serious and increasingly prevalent healthcare-associated infection. The pathogenesis of CD infection (CDI) involves the acquisition of CD with a concurrent disruption of the native gut flora. Antibiotics are a major risk although other contributing factors have also been identified. Clinical management combines discontinuation of the offending antibiotic, initiation of CD-specific antibiotic therapy, probiotic agent use, fecal microbiota transplantation (FMT), and surgery as the “last resort” option. The aim of this study is to review short-term clinical results following the implementation of FMT protocol (FMTP) at our community-based university hospital.Methods:After obtaining Institutional Review Board and Infection Control Committee approvals, we implemented an institution-wide FMTP for patients diagnosed with CDI. Prospective tracking of all patients receiving FMT between July 1, 2015, and February 1, 2017, was conducted using REDCap™ electronic data capture system. According to the FMTP, indications for FMT included (a) three or more CDI recurrences, (b) two or more hospital admissions with severe CDI, or (c) first episode of complicated CDI (CCDI). Risk factors for initial infection and for treatment failure were assessed. Patients were followed for at least 3 months to monitor for cure/failure, relapse, and side effects. Frozen 250 mL FMT samples were acquired from OpenBiome (Somerville, MA, USA). After 4 h of thawing, the liquid suspension was applied using colonoscopy, beginning with terminal ileum and proceeding distally toward mid-transverse colon. Monitored clinical parameters included disease severity (Hines VA CDI Severity Score or HVCSS), concomitant medications, number of FMT treatments, non-FMT therapies, cure rates, and mortality. Descriptive statistics were utilized to outline the study results.Results:A total of 35 patients (mean age 58.5 years, 69% female) were analyzed, with FMT-attributable primary cure achieved in 30/35 (86%) cases. Within this subgroup, 2/30 (6.7%) patients recurred and were subsequently cured with long-term oral vancomycin. Among five primary FMT failures (14% total sample), 3 (60%) achieved medical cure with long-term oral vancomycin therapy and 2 (40%) required colectomy. For the seven patients who either failed FMT or recurred, long-term vancomycin therapy was curative in all but two cases. For patients with severe CDI (HVCSS ≥3), primary and overall cure rates were 6/10 (60%) and 8/10 (80%), respectively. Patients with CCDI (n = 4) had higher HVCSS (4 vs. 3) and a mortality of 25%. Characteristics of patients who failed initial FMT included older age (70 vs. 57 years), female sex (80% vs. 67%), severe CDI (80% vs. 13%), and active opioid use during the initial infection (60% vs. 37%) and at the time of FMT (60% vs. 27%). The most commonly reported side effect of FMT was loose stools.Conclusions:This pilot study supports the efficacy and safety of FMT administration for CDI in the setting of a community-based university hospital. Following FMTP implementation, primary (86%) and overall (94%) nonsurgical cure rates were similar to those reported in other studies. The potential role of opioids as a modulator of CDI warrants further clinical investigation.

Early Rescue from Acute Severe Clostridium Difficile: A Novel Treatment Strategy.

Severe Clostridium difficile infections (CDI) can lead to significant impediments to effective treatment. We developed a novel treatment protocol utilizing bedside gastrointestinal lavage (GIL) for the management of patients with severe, complicated CDI. We describe the development and early outcomes of non-operative bedside GIL in hospitalized patients with severe, complicated CDI following the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL) framework at the Idea stage. We compared our results with those of a cohort of patients managed with colectomy. We conducted a retrospective cohort study of hospitalized patients with severe, complicated CDI who failed conventional medical therapy and were referred for surgical consultation at two academic tertiary-care hospitals between January 2009 and January 2015. After surgical assessment, the attending surgeon decided to proceed either with bedside GIL or directly to colectomy. Bedside GIL involved nasojejunal tube insertion followed by flushing with 8 L of polyethylene glycol 3350/electrolyte solution over 48 h. Both patient groups received standard medical treatment with vancomycin 500 mg q 6 h enterally and metronidazole 500 mg intravenously three times daily for 14 d. The main outcomes of interest were the incidence of colectomy, complications, and mortality rate. Nineteen and seventeen patients underwent GIL and direct colectomy, respectively. There were no significant differences between the groups in terms of demographics, American Society of Anesthesiologists class, disease severity, need for intensive care unit admission, mechanical ventilation, vasopressor use, serum lactate concentration, or proportion presenting with hypotension, acute kidney injury, or a white blood cell count >16,000/mcL or <4,000/mcL (p > 0.1). The in-hospital mortality rate was 26% (5/19) and 41% (7/17) for the GIL and colectomy groups, respectively (p = 0.35). Only one patient in the GIL group failed the protocol, requiring colectomy. There were no significant differences in complications in the two groups. Bedside GIL appeared to be safe for the treatment of patients with severe, complicated CDI who had failed conventional medical therapy. It did not appear to increase the risk of morbidity or death compared with the traditional strategy of proceeding directly to colectomy.

Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia.

AIMTo evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) population.METHODSAfter IRB approval, all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified. Medical charts were reviewed for demographics, clinical information, development of CDI, complications of CDI, and mortality. Patients with CDI, defined as having a positive stool PCR done for clinical suspicion of CDI, were compared to those without CDI in order to identify predictors of disease. A t-test was used for comparison of continuous variables and chi-square or Fisher’s exact tests were used for categorical variables, as appropriate.RESULTSTwo hundred and twenty-three patients (60.1% male, mean age 61.3 years, 13% MDS, 87% AML) had 594 unique hospitalizations during the study period. Thirty-four patients (15.2%) were diagnosed with CDI. Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001), prior diagnosis of CDI (P < 0.0001), receipt of cytarabine-based chemotherapy (P = 0.015), total days of neutropenia (P = 0.014), and total days of hospitalization (P = 0.005). Gender (P = 0.10), age (P = 0.77), proton-pump inhibitor use (P = 0.73), receipt of antibiotics (P = 0.66), and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSIONCDI is common in the MDS/AML population. Factors significantly associated with CDI in this population include low albumin, prior CDI, use of cytarabine-based chemotherapy, and prolonged neutropenia. In this study, we have identified a subset of patients in which prophylaxis studies could be targeted.

Improved Success Rate of Fecal Microbiota Transplantation With Dual Method of Administration in 2 Patients With Antibiotic-Refractory Complicated Clostridium difficile Infection in ICU Setting

Fecal microbiota transplantation (FMT) is well recognized as a treatment modality with a 90% success in patients with recurrent Clostridium difficile infection (RCDI). More recently, colonic FMT has been applied to severe CDI patients by Fisher et al with a success rate of 42%. We present two cases of complicated CDI in the setting of septic shock treated with a session of combined enteral and colonic FMT resulting in dramatic clinical response. 71-year-old man with a history of Clostridium difficile infection (CDI) presented with a 9-day history of profuse watery diarrhea associated with altered mental status and hypotension was admitted to ICU. Lab data showed elevated WBC, lactate and BUN. Stool testing for Clostridium difficile toxin and antigen was positive. He was started on IV metronidazole and oral vancomycin as well as vasopressor and intravenous hydration. His diarrhea persisted, and he became febrile with rising WBC to 44,000. Due to abdominal distention and pain, surgery suggested colectomy. Gastroenterology was consulted for alternative therapy with FMT. Colonoscopy showed severe pan-pseudomembranous colitis (Figure 1.1 and 1.2). Fecal filtrate from the hospital's stool bank was administered. 40 mL of filtrate was delivered into the jejunum and 60 mL of fecal filtrate was infused into the ascending colon. Within 72-hours, the patient's WBC improved along with mental status and hypotension with resolution of diarrhea. 51-year-old-man with a history of compensated liver cirrhosis was transferred to our hospital for septic shock associated with CDI. He was refractory to metronidazole, oral and rectal vancomycin as well as fidaxomicin. The patient was not a surgical candidate for colectomy due to clinical instability. Colonoscopy showed severe colitis in the rectosigmoid junction (Figure 1.3). Fecal filtrate of 100 mL was infused into the jejunum and 200 mL into the ascending colon. Within 48-hours, patient had a decline in WBC and vasopressor requirement. Patient had remarkable improvement in diarrhea within 48-hours. FMT has been reported as an alternative to subtotal colectomy in complicated CDI patients with dramatic therapeutic response. However, the efficacy appears to be low in the ICU setting. Delivery of FMT by combined enteral and colonic routes may improve success rates as it did in our two cases. Additional studies are needed to examine the effect of FMT by dual method of administration in complicated CDI patients.Figure: Pseudomembranous colitis in the transverse colon.Figure: Pseudomembranous colitis in the descending colon.Figure: Ulcerative proctitis.

External validation of clinical scores to predict complications of Clostridium difficile infection

Background Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea. About one in 5 patients with CDI (median 18%) develop a complication (cCDI), including mortality. Many predictive scores have been published to identify patients at risk of cCDI but none is currently recommended for clinical use and few were validated. We conducted an external validation study of predictive tools for cCDI.MethodsPredictive tools were identified through a systematic review. We included those reporting at least an internal validation process. We performed the external validation on a multicenter prospective cohort of 1380 Canadian adults with confirmed CDI. Most cases were elderly (median age 71), had a healthcare facility-associated CDI (90%), and cCDI occurred in 8%. NAP1 strain was found in 52%. The performance of each scoring system was analyzed using individual outcomes. Modifications in predictors were made to match available data in the validation cohort.ResultsWe assessed 3 predictive scores and one predictive model. The performance (95% CI) of higher thresholds are shown in the Table. All scores had a low sensitivity and PPV, and moderate specificity and NPV. The model of Shivashankar 2013 (age, WBC> 15, narcotic use, antacids use, creatinine ratio > 1.5) predicted 25% probability of cCDI. All showed similar AUC (0.63–0.67).Study, outcome (%)Predictors (points)Sen %Spe %PPV %NPV %LR+Accuracy (%)Na 2015 (2–3 patients) ICU admission, megacolon, colectomy, attributable 30-day death (8%).Age ≥ 65 (1) WBC ≥ 20 (1) Creatinine ≥ 2 mg/dL (1)46 (36–55)87 (85–89)23 (17–29)95 (94–96)3.5 (3–4)84 (82–86)van der Wilden 2013 (≥ 6 patients) ICU, colectomy, attributable 30-day death (7%).Age >70 (2) WBC ≥20 or ≤2 (1) Cardiorespiratory failure (7) Abdominal pain (6)*61 (51–57)55 (52–58)9 (7–11)95 (93–97)1.35 (1.3–1.4)55 (53–58)Hensgens 2013 (≥ 4 patients) ICU, colectomy, all-cause 30-day death (15%).Age (50–84, ≥ 85) (1, 3) Diagnosis in ICU (3) Abdominal surgery (-3) MAP ≤65mmHg (2)* Diarrhea (2)26 (19–32)90 88–92)30 24–37)87 85–89)2.5 2–3)80 (78–82) *ModifiedConclusionThe predictive tools included in our study showed moderate performance in a validation cohort with a low rate of cCDI and high proportion of NAP1 strains. Further research is needed to develop an accurate predictive tool to guide clinicians in the management of CDI.Disclosures J. Powis, Merck: Grant Investigator, Research grant; GSK: Grant Investigator, Research grant; Roche: Grant Investigator, Research grant; Synthetic Biologicals: Investigator, Research grant

Derivation and Validation of a Clinical Prediction Rule for Complications of Clostridium difficile Infection Using a Multicenter Prospective Cohort

Background Clostridium difficileinfection (CDI) outbreaks were associated with increase in unfavorable outcomes. Identifying and predicting risk of developing complications (cCDI) early in the course of illness could improve clinical decision-making. We developed and validated a prediction rule for cCDI.MethodsAdult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and followed for 90 days. Data within 48h of CDI diagnosis were collected: demographics, underlying illnesses, past medical and drug history, clinical signs, blood tests, and strain ribotype. cCDI was defined as one or more of: colonic perforation, toxic megacolon, colectomy, need of vasopressors, ICU admission due to CDI, or if CDI contributed to 30-day death. Predictors’ selection was supported by experts’ opinion suggesting 17 clinical criteria. Cross-validation technique was used (2:1 ratio) and multivariable logistic regression for predictive modeling in the derivation subset. The optimal model was assessed by area under ROC curve (AUC) and prediction error (PE). A predictive score was built by assigning points proportional to adjusted risk estimates.ResultsAmong 1380 patients enrolled, 1050 were used for predictive modeling (median age 70 years and one-third infected by ribotype 027 strains). Cases were split into training (n = 700) and validation sets (n = 350). A cCDI occured in 8% and 6.6% respectively. The optimal model with a PE of 5% and an AUC of 0.84 in the validation set included WCC (< 4, 12–19.9, or ≥20 × 109/L), BUN≥11 mmol/L, serum albumin <25 g/L, heart rate > 90/minute, and respiratory rate >20/minute. A predictive score of min 0 and max 13 points was derived. A score ≥7 points was associated with 70% cases of cCDI, showed 68% sensitivity (95% CI, 55–80) in the derivation set and 70% (51–88) in the validation set, a specificity of 73% (69–76) and 76% (72–81) respectively, 17% PPV (9–25), and 97% NPV (95–99) in both sets.ConclusionUsing a large multicenter prospective cohort and robust modeling approach, we derived a predictive score that included easily available measures at the bedside. The score showed acceptable performance. Further validation is needed on cohorts with different characterstics (non-outbreak setting, higher rate of cCDI). Other approaches such as combination of biomarkers could be more predictive of cCDI.Disclosures J. Powis, Merck: Grant Investigator, Research grant; GSK: Grant Investigator, Research grant; Roche: Grant Investigator, Research grant; Synthetic Biologicals: Investigator, Research grant

Inpatient Fecal Microbiota Transplant Program Decreases Mortality and Colectomy in Severe and/or Complicated Clostridium difficile Infection

Introduction: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridium difficile infection (CDI). However, surgery still remains the standard of care for severe and severe-complicated CDI refractory to medical therapy despite the resultant high rates of post-surgical mortality at 19-57%. We aimed to measure the impact of a previously described and highly efficacious inpatient sequential FMT protocol on CDI-related mortality and colectomy rates. Methods: CDI associated hospitalizations were identified from electronic medical records before (2009-2012) and after FMT program implementation (2013-2016) at a single tertiary care referral center. Baseline characteristics and outcomes for CDI hospitalizations were retrospectively collected through detailed chart reviews and FMT database analysis. Severe and severe-complicated CDI was classified per ACG guidelines; a subgroup of severe and severe-complicated CDI patients with no response to vancomycin after ≥ 5 days on therapy were defined as refractory. The inpatient FMT program's impact on outcomes such as CDI-related 30-day mortality, CDI-related colectomy, length of stay, and 30-day readmission rates were analyzed using piecewise logistic regression. Results: Between 2009 and 2016, there were 2,826 CDI admissions; 429 met criteria for severe and severecomplicated CDI, among these 110 were refractory. After FMT program initiation, FMT was administered during 128 admissions leading to lower rates of CDI-related mortality and colectomy for patients with severe or severe-complicated CDI (Figure 1) and for those with refractory CDI (Figure 2). Overall, CDI-related mortality decreased from 10.2% to 4.5% (P=0.021) in severe and severe-complicated CDI, and from 43.2% to 12.1% (P<0.001) in refractory CDI admissions. CDI-related colectomy also decreased significantly: from 6.8% to 2.7% (P=0.042) in severe and severe-complicated CDI, and from 31.8% to 7.6% (P=0.001) in refractory CDI. While 30-day readmission rates did not differ after FMT program implementation, the median length of stay for all CDI-related hospitalizations decreased from 9 days (IQR: 5-18) to 8 days (IQR: 4-17) (P=0.01).FigureFigureConclusion: Implementation of an inpatient FMT program was associated with significantly decreased rates of CDI-related mortality and colectomy in severe and severe-complicated CDI as well as therapyrefractory CDI at an institutional level.