Clostridium Difficile Infection In Patients Research Articles

S0093 Clostridium difficile Infection in Patients With Chronic Pancreatitis: Comparison of Patient Characteristics and Outcomes

INTRODUCTION: Patients with Chronic pancreatitis (CP) have high rates of unplanned recurrent hospitalizations. Long-term hospital stay significantly increases risk of Clostridium difficile infection (CDI) which is among leading cause of gastrointestinal death. The aim of this study is to examine clinical characteristics and outcomes of CP patients with CDI. METHODS: Nationwide Inpatient Sample database was queried from October 2015 to December 2017 using ICD 10 to identify patients with CP and CDI (age ≥18 years). SAS 9.4 was used for analysis to determine baseline characteristics, Elixhauser comorbidities & outcomes among CP patients with CDI and non-CDI groups. Further, multivariate logistic regression analysis was performed to analyze adjusted mortality. RESULTS: Among 159,615 CP patients, 4,550 (2.85%) had concomitant CDI. Female gender was higher among CP with CDI patients (53.3%), while male in non-CDI group (57.6%, P < 0.0001). A majority of CP patients in non-CDI group were <65 years age (87.7%) as compared to CDI (78.4%, P < 0.0001). Medicare (42.1%) was main form of insurance in CDI while Medicaid (31.4%, P < 0.0001) in non-CDI patients. CP with CDI patients reported significantly higher prevalence of comorbidities including diabetes mellitus, liver diseases, renal failure, weight loss, fluid & electrolyte disorders, and coagulopathy. Complications such as dehydration and electrolyte disorders (63.1% vs 39.2%), septicemia (5.2% vs 1.2%), ascites (4.2% vs 2.3%), hypoalbuminemia (2.6% vs 0.9%) were significantly higher in CDI group. While, alcohol abuse (30.9% vs 37.8%, P < 0.0001) and acute pancreatitis (35.9% vs 82.9%, P < 0.0001) were higher in non-CDI group. Outcomes showed significantly higher in-hospital mortality (0.8% vs 0.2%, P < 0.0001; adjusted OR(95% CI): 1.49 (1.04–2.13), P = 0.02), longer median length of stay (5 vs 3 days, P < 0.0001) ,higher median hospitalization cost (8802 vs 5921, P < 0.0001) & lower disposition to home (68.8% vs 85.1%, P < 0.0001) in CP patients with CDI. CONCLUSION: CP patients with CDI has higher comorbidities than non-CDI group. Presence of CDI in CP patients leads to higher mortality rate, longer length of stay and higher hospitalization cost. Future studies should be targeted towards prevention of CDI in patients with CP.Table 1.: Patient-Level Characteristics of Chronic Pancreatitis with Clostridium Difficile Infection (CDI) versus Chronic Pancreatitis with Non-CDITable 2.: In-hospital Outcomes among Chronic Pancreatitis with Clostridium Difficile Infection (CDI) versus Chronic Pancreatitis with Non-CDI

Outcomes of Neutropenic Patients with Clostridium difficile Infection

Background: Data from Clostridium difficile infection (CDI) in neutropenic patients are still scarce. Objective: To assess outcomes of CDI in patients with and without neutropenia. Methods: The study included a retrospective cohort of adult patients at 3 academic hospitals between January 2013 and December 2017. The 2 study arms were neutropenic patients (neutrophil count &lt;500/mm3) and nonneutropenic patients with confirmed CDI episodes. The primary outcome evaluated the composite end point of all-cause in-hospital mortality, intensive care unit (ICU) admissions, and treatment failure at 7 days. The secondary outcome evaluated hospital length of stay. Results: Of 962 unique cases of CDI, 158 were neutropenic (59% men) and 804 were nonneutropenic (46% men). The median age was 57 years (IQR, 44–64) in the neutropenic group and 68 years (IQR, 56–79) in the nonneutropenic group. The median Charlson comorbidity score was 5 (IQR, 3–7.8) and 4 (IQR, 3–5) in the neutropenic and nonneutropenic groups, respectively. Regarding severity, 88.6% versus 48.9% were nonsevere, 8.2% versus 47% were severe, and 3.2% versus 4.1% were fulminant in the neutropenic and nonneutropenic groups, respectively. Also, 63% of patients (60.9% in nonneutropenic, 65.2% in neutropenic) were exposed to proton-pump inhibitors. A combination CDI treatment was required in 53.2% of neutropenic patients and 50.1% of nonneutropenic patients. The primary composite end point occurred in 27% of neutropenic patients versus 22% of nonneutropenic patients (P = .257), with an adjusted odds ratio of 1.30 (95% CI, 0.84–2.00). The median hospital length of stay after controlling for covariates was 21.3 days versus 14.2 days in the neutropenic and nonneutropenic groups, respectively (P &lt; .001). Complications (defined as hypotension requiring vasopressors, ileus, or bowel perforation) were seen in 6.0% of the nonneutropenic group and 4.4% of the neutropenic group (P = .574), with an adjusted odds ratio of 0.61 (95% CI, 0.28–1.45). Conclusions: Neutropenic patients were younger and their cases were less severe; however, they had lower incidences of all-cause in-hospital mortality, ICU admissions, and treatment failure. Hospital length of stay was significantly shorter in the neutropenic group than in the nonneutropenic group.Funding: NoneDisclosures: None

S0164 Clostridioides difficile Infection in COVID-19 Patients

INTRODUCTION: Gastrointestinal manifestations including diarrhea are prevalent among COVID-19 patients. Given the frequent use of broad-spectrum antibiotics, COVID-19 patients are also at substantial risk for hospital-acquired diarrheal illnesses. We aimed to evaluate the prevalence and outcomes of Clostridioides difficile infection (CDI) among hospitalized patients with COVID-19. METHODS: This was a retrospective cohort study of patients hospitalized with laboratory confirmed COVID-19 across 9 hospitals in Massachusetts in 3/11/2020–4/2/2020. All patients underwent stool testing for CDI with glutamate dehydrogenase (GDH) and ELISA immunoassay (EIA) for toxin. Inconclusive GDH/EIA with high clinical suspicion were confirmed with polymerase chain reaction (PCR). Positive CDI rate in COVID-19 patients was compared with local historical inpatient CDI testing data from 2019. Outcomes and mortality were also compared amongst COVID-19 patients with and without CDI. RESULTS: Of the 390 hospitalized patients with COVID-19, 97 (24.9%) were tested for CDI and included in the study. All patients received ≥2 antibiotics (median = 4, IQR 2–5.5). Compared to historical controls, COVID-19 patients did not have higher overall CDI positive rate (5.2% [n = 5] vs 9.8% [n = 280]; P = 0.16). Specifically, GDH/EIA positive rates were similar between both groups (5.2% vs 5.3%). There were no statistically significant differences in median antibiotic use, PPI use, laboratory data or need for ICU care between CDI vs non-CDI patients. However, all-cause mortality was significantly higher among CDI patients (80% vs 12.2%; P < 0.0001) Table 1. CONCLUSION: The prevalence of CDI was not higher among COVID-19 patients despite widespread use of broad-spectrum antibiotics. With strict isolation of COVID-19 patients in most hospitals, together with aggressive hand washing and donning/doffing protocols, it is possible that such rigorous measures resulted in the unintended benefit of reducing nosocomial CDI. However, albeit a limited sample size, development of CDI was associated with significantly worse outcomes and higher mortality. As such, early CDI testing should be implemented among patients with COVID-19 to ensure prompt diagnosis and management.Table 1.: (A) Clostridioides difficile infection stool testing of COVID-19 patients compared to all inpatient CDI tests in 2019. (B) Hospitalization course and outcomes of COVID-19 patients with and without CDI. * Stool PCR only performed with GDH/EIA indeterminant samples

S0829 Vitamin D Deficiency Associated With Clostridioides difficile Infection in Inflammatory Bowel Disease Admissions: Insights From the National Inpatient Sample Database

INTRODUCTION: Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality in inflammatory bowel disease (IBD) population. Well established risk factors for CDI include recent hospitalization, long term use of antibiotics, and chronic immunosuppression. Additionally, recent reports suggest that vitamin D-deficiency plays an important role in CDI susceptibility. This study aimed to evaluate the relationship between vitamin D deficiency and CDI in patients admitted with IBD exacerbation. METHODS: We queried the National Inpatient Sample database 2006–2014. We selected patients with a primary diagnosis of ulcerative colitis (UC), Crohn’s disease (CD), or IBD-related complications using the appropriate ICD-9 codes. We identified patients with the diagnosis of intestinal CDI. Categorical variables were compared using Chi-square. Predictors of Vitamin D deficiency and CDI were evaluated by multivariate logistic regression. RESULTS: A total of 1,000,218 weighted discharges with a primary diagnosis of UC, CD, or IBD-related complications were analyzed. 36.3% of the cases had UC, 64% had CD and 0.7% had undetermined IBD. Among all the cases 6.1% had a diagnosis of CDI. Patients with CDI were older (53.8 years vs 45.9 years, P < 0.001) and predominantly female (59.5% vs 40.5% P < 0.001). Older age, female gender (aOR: 1.18, P < 0,001), diagnosis of UC, vitamin D deficiency (aOR: 1.73, P < 0,001), long-term use of steroids (aOR: 1.2, P < 0,001), and antibiotics (aOR: 3.02, P < 0,001) were independent predictors of CDI among the IBD population. Patients with CD (aOR: 0.66, P < 0,001), long-term use of ASA (aOR: 0.93, P = 0.006) and non-steroidal anti-inflammatory drugs (aOR:0.52, P < 0,001) were less likely to have CDI during hospitalization. CONCLUSION: Vitamin D is involved in innate and acquired immunity and plays an important role on gut health. The deficiency of vitamin D in IBD patients has been associated with increased disease activity and poor outcomes. Only a few studies have examined an association between vitamin D levels and susceptibility to CDI in the IBD population. The proposed mechanism is decreased levels of cathelicidin, an antimicrobial peptide that inhibits the effect of C difficile toxin, which production is stimulated by vitamin D. Our study showed that vitamin D deficiency is a predictor of CDI in patients admitted with IBD exacerbation. Its main implication is the potential impact vitamin D supplementation can play in reducing the rates of CDI among the IBD population.Figure 1.: Percentages of the type of IBD among discharges for IBD exacerbation from 2006 to 2014.Table 1.: Summary of demographic characteristics of all cases with a primary discharge diagnosis of IBD: Nationwide Inpatient Database from 2006 to 2014Table 2.: Independent predictors of CDI in patients with a primary discharge diagnosis of IBD: multivariate logistic regression analysis in the Nationwide Inpatient Database in 2006–2014

Clostridium difficile Infection Prevention Bundle Implementation

Background: The optimal prevention of healthcare onset Clostridium difficile infection (CDI) has been a challenging one in an acute tertiary-care hospital with limited number of single rooms. Asymptomatic patients with CDI are nursed in open wards but tagged with a green sticker to alert staff of their status. This signal prompts cleaning staff to use 5,000 ppm sodium hypochlorite to clean environmental surfaces in the multibed room and to continue with modified contact precautions. Methods: We conducted a survey on infection prevention measures used in the management of CDI patients over 2 weeks among senior nurse managers, clinicians, and registered nurses in 38 inpatient wards. We categorized the survey results into 4 types of practices: established practices, nonestablished practices (easy implementation), nonestablished practices (lack of resources), and nonestablished practices (staff resistance). We then identified barriers to determine reasons for resistance to nonestablished practices before the implementation of the CDI bundle in May 2019. The bundle comprised the following components: contact precautions, antimicrobial stewardship, isolation of CDI patient with diarrhea in single room, environment, and equipment hygiene. Following the survey, we enhanced the signage for CDI patients to be more obvious. Monthly, we monitored the incidence of HO-Clostridium difficile to assess effectiveness of implementation measures. Results: Nonestablished practices (easy implementation) included uncertainty of diarrhea definition and the recommended environmental hygiene disinfectant, lack of understanding of the importance of complying to personal protective equipment (PPE), and inconsistency in conveying CDI status. Among nonestablished practices (lack of resources), shortage of isolation beds for CDI patients with diarrhea and unavailability of electronic alert system for CDI patients within the institution are the major issues faced by clinical staff. Unavailability of CDI indicator stickers, contact precaution posters, and sporicidal wipes were noted in 6 medical and surgical wards. Nonestablished practices (staff resistance) were related to the time taken to don full PPE and reluctance to arrange for an isolation bed due to increased workload and unavailability of isolation beds. A shift was noted in the control chart for HO-Clostridium difficile after the implementation of the CDI bundle in May 2019. Conclusions: The categorization of practices into established and nonestablished practices can help to identify barriers that may interfere with successful implementation of an infection prevention bundle.Funding: NoneDisclosures: None

Effect of Testing Methods on Incidence of Clostridioides difficle Infection Rates in Veterans’ Affairs Medical Centers

Background: Healthcare-associated Clostridioides difficile infection (CDI) rates have been decreasing in Department of Veterans’ Affairs (VA) acute-care medical facilities since the CDI Prevention Initiative began in 2012. Assessment of rates, however, is complicated by changing surveillance definitions and diagnostics. Over the past 2 years, the VA has adopted the less stringent surveillance definitions of the NHSN for hospital-onset healthcare-facility–associated (HO-HCFA) CDI (onset on or after day 4 of hospitalization) than was originally used (&gt;48 hours after admission). New diagnostic testing methods have been developed, but variabilities in the reliability of testing methods for the diagnosis of CDI in patients have been detected, thus not yielding a gold standard test. As a result, some facilities use nucleic acid amplification testing (NAAT) for CDI diagnosis and reporting whereas others use a 2-step process of NAAT followed by a toxin enzyme immunoassay (EIA) test, with the latter determining positivity for reporting (as allowed by the NHSN). We reviewed CDI rates at facilities performing one-step and two-step testing to determine whether the testing protocol may be influencing CDI rate reporting. Methods: Data on HO-HCFA CDI rates entered monthly in fiscal year (FY) 2018 (October 2017 through September 2018) and FY2019 (October 2018 through September 2019) by each acute-care facility into the VA Inpatient Evaluation Center (IPEC) database were analyzed. HO-HCFA CDI rates in facilities that used NAAT in FY2018 and switched to in the 2-step NAAT plus EIA in FY2019 were compared to rates in facilities used NAAT alone for both FY2018 and FY2019. Statistical regression analysis was performed. Results: From FY 2018 through FY2019, 70 facilities performed NAAT for the entire 2-year period. Overall, 7 facilities performed NAAT for FY 2018 and then switched to NAAT + EIA in FY2019. We detected no significant decrease in HO-HCFA CDI rates in FY 2018 when both groups were using NAAT (P = 0.21) (Fig. 1). However, in FY2019, there was a significant decrease in HO-HCFA CDI rates for those facilities that performed the 2-step testing versus those facilities that continued to use strictly NAAT alone (P &lt; .0001). Conclusions: HO-HCFA CDI rates decreased for those VA acute-care facilities that switched to 2-step testing, and this finding highlights implications for assessing rates over time. Given the variable reliability of the toxin test, individual patient consideration for therapeutic decisions is reasonable.Funding: NoneDisclosures: None

S3224 Comparison of Patient Characteristics and Outcomes of Clostridium difficile Infection in Patients With Ulcerative Colitis

S3224 Comparison of Patient Characteristics and Outcomes of Clostridium difficile Infection in Patients With Ulcerative Colitis

S0665 Clostridium difficile Infection in Patients With Ulcerative Colitis Treated With Tofacitinib in the Ulcerative Colitis Program: An Update as of May 2019

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Patients (pts) with UC are susceptible to C. difficile infection (CDI) (1). In the tofacitinib UC clinical program, previous analyses showed CDI rates among tofacitinib-treated pts to be similar or numerically lower than placebo (PBO)-treated pts and pts treated with immunomodulators and TNFi in a generally comparable claims-based observational cohort (2). Here, we present an updated analysis of CDI in the tofacitinib UC clinical program. METHODS: CDI events were evaluated from 4 randomized, PBO-controlled studies (Phase [P]2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951]; 1 maintenance P3 study [NCT01458574]) and an ongoing, open-label, long-term extension (OLE) study (NCT01470612). 3 cohorts were analyzed: Induction (P2/P3 induction studies), Maintenance (P3 maintenance study) and Overall (pts receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3 or OLE studies; analyzed by pts receiving ≥ 1 dose of tofacitinib and predominant dose [PD; 5 or 10 mg BID based on average daily dose <15 mg or ≥ 15 mg, respectively]; data as of May 2019, database not locked). Proportions and incidence rates (unique pts with events per 100 pt-yrs [PY] of exposure) of CDI were evaluated. All pts underwent CDI screening; a positive test excluded pts from program entry. RESULTS: The Overall Cohort comprised 1,157 pts who received ≥ 1 dose of tofacitinib 5 or 10 mg BID, representing 2,581 PY of tofacitinib exposure and up to 6.8 yrs of treatment. CDI occurred in 3 pts in the Induction Cohort (PBO, n = 1; tofacitinib 10 mg BID, n = 2), 3 pts in the Maintenance Cohort (PBO, n = 3; CDI occurred 68, 81 and 98 days following initiation of PBO) and 9 pts in the Overall Cohort (PD tofacitinib 10 mg BID, n = 9; Table 1). Overall Cohort pts with CDI were mild (n = 4) or moderate (n = 5) in severity; 6 pts continued study treatment without interruption, 1 temporarily discontinued and 2 permanently discontinued. CDI resolved with treatment in 8 pts and CDI was still present in 1 pt at the time of study discontinuation. Two events were reported as serious AEs due to hospitalization. CONCLUSION: In the tofacitinib UC program, CDI rates among pts receiving tofacitinib have remained stable since the previous data cut (2) and are comparable to those reported for other advanced therapies (3).Table 1

S0152 Successful Bacterial Engraftment Identified by Next Generation Sequencing Following Fecal Microbiota Transplantation for Clostridioides difficile Infection

INTRODUCTION: Fecal Microbiota Transplantation (FMT) has become a standard therapy for toxigenic Clostridioides difficile infection (CDI). In this study we sought to investigate the utility of next generation sequencing (NGS) to characterize the extent of bacterial engraftment following FMT in CDI patients. FMT efficacy was elucidated utilizing metagenomic analyses to identify microbiota similarities among the cohort with that of the healthy Donor’s. METHODS: NGS was performed on fecal samples from study participants (n = 7). Patient stools were collected both prior to and after FMT. From the stool specimens, DNA was extracted, prepared, and sequenced utilizing shotgun methodology on Illumina’s NextSeq 550 System. Metagenomic analyses were performed to characterize the intestinal microbiota of the study participants. RESULTS: Principal Component Analysis (Figure 1) of the microbiota from study participants was executed to investigate the variance among them. PC1 and PC2 captured 52% and 34% of the variation respectively, and clearly highlighted the shift in the patients’ gut flora compared to their microbiota prior to engraftment. The relative abundances (Figure 2) of the bacterial taxa in the samples elucidated the compositional resemblance of Patients 1 and 2 after their FMT with that of their Donor. The pre-FMT relative abundance of Firmicutes in Patient 1 and Patient 2 were 51% and 15%, whereas after FMT they matched closely with the Donor (73%) at 63% and 60%. The 16% in Patient 3 was suggestive of a failed engraftment, as it was not close to that of the Donor. Similarly, Lachnospiraceae in the Donor (15%) matched with the post-FMT of Patient 1 (19%) and Patient 2 (27%), whereas it did not with Patient 3 (0.36%). The Bray-Curtis Distance Matrix (Figure 3) was utilized to profile the overall microbiota from the study participants. The ordination matrix identified the similarity of Patient 1 and 2 post-FMT with that of the Donor (dark blue squares), clustering in distinct coordinates. It also captured that Patient 3 was the most dissimilar among the post-FMT cohort. CONCLUSION: NGS provides a unique opportunity to assess the microbiomes of patients both prior to, and after FMT; and for the evaluation of the bacterial engraftment. Metagenomic characterization of the gut flora, along with monitored care and patient tracking, collectively elucidate the potential of NGS to provide clinical insight and guide outcomes.Figure 1.: Principal Component Analysis (PCA) of the microbiota from the Donor, pre-FMT patients, and post-FMT patients. The samples circled in red highlight the similarity of Patient 1 and 2 following their FMTs with that of their Donor.Figure 2.: Relative abundances (%) of bacteria in stool samples of Donor, post-FMT and pre-FMT samples at the Phylum and Family level.Figure 3.: Bray-Curtis Distance Matrix of the microbiota from Donor, pre-FMT and post-FMT patients. The samples boxed in red highlight the similarity of Patient 1 and 2 following their FMTs with that of their Donor.

S0153 Relapsing Clostridium difficile Infection: Resolution With Combined Patient Choice Fecal Microbiota Transplantation, Vancomycin Taper, and Vancomycin Suppression

INTRODUCTION: Clostridium difficile infection (CDI) results in approximately a half a million cases and 15,000 deaths annually in the United States. Relapse rates vary between 20-50% and account for frequent readmissions and morbidity. Application of treatment modalities for relapsing cases resulting in complete resolution is reported here. METHODS: An observational analytical cohort study was done from June 2014 to December 2018 by offering options to patients for treatment of their CDI relapse. Each chose between Fecal Microbiota Transplantation (FMT; N = 52), Vancomycin po 6-week taper (VTa; N = 4), or Vancomycin 125 mg po daily 6-month suppression (VSu; N = 18). The FMT was given either as a liquid NG instillation (FMT-L) twice 12-24 hours apart (N = 47) or 20 capsules (FMT-C) given over 90 minutes (N = 5). Patients were followed for at least 8 weeks after treatment with readmissions tracked for 6 months in all cases. Fisher’s Exact Test was used for statistical significance. RESULTS: No patient was readmitted to the hospital for CDI associated problems during the term of this study. More men choose po Vancomycin with more women choosing FMT (VTa/VSu Female 38%: Male 62% and FMT Female 80%: Male 20%; P < 0.01). Overall initial response rate was 90%. Resolution of CDI was highest among the FMT-L (95.7 %; N = 45/47; P = 1) and the VSu (94%; N-17/18; P = 1). The VTa group had 75% resolution (N = 3/4; nsd). The FMT-C arm showed a 40% success rate (N = 2/5; nsd). Treatment failures (N = 7) chose re-treatment with 6 cases repeating VTa having one relapse responding to FMT-L. One relapse in the VSu group responded to a 6 months daily Vancomycin suppressive course. The only statistically significant difference was in male to female ratios. Cost of therapy was highest for FMT-L $2326, FMT-C $1870, VSu $965, and VTa $700 average per course. CONCLUSION: This report integrates options in treatment that follows the relapsing CDI patient to complete resolution. This eliminated hospital readmission and further morbidity. Allowing the patient freedom of treatment option was well received. Of the treatment arms, FMT-L and VSu were equivalent in outcomes, followed by VTa and FMT-C. FMT-L as 2 instillations provides higher response rates than previously reported. This was a small sample size, however primary study endpoints of no hospitalizations and complete resolution were attained.

Microbiota in Clostridioides difficile-Associated Diarrhea: Comparison in Recurrent and Non-Recurrent Infections.

Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea, especially in hospitalized elderly patients, representing a global public health concern. Clinical presentations vary from mild diarrhea to severe pseudomembranous colitis that may progress to toxic megacolon or intestinal perforation. Antibiotic therapy is recognized as a risk factor and exacerbates dysbiosis of the intestinal microbiota, whose role in CDI is increasingly acknowledged. A clinically challenging complication is the development of recurrent disease (rCDI). In this study, using amplicon metagenomics, we compared the fecal microbiota of CDI and rCDI patients (sampled at initial and recurrent episode) and of non-infected controls. We also investigated whether CDI severity relates to specific microbiota compositions. rCDI patients showed a significantly decreased bacterial diversity as compared to controls (p < 0.01). The taxonomic composition presented significant shifts: both CDI and rCDI patients displayed significantly increased frequencies of Firmicutes, Peptostreptococcaceae, Clostridium XI, Clostridium XVIII, and Enterococcaceae. Porphyromonadaceae and, within it, Parabacteroides displayed opposite behaviors in CDI and rCDI, appearing discriminant between the two. Finally, the second episode of rCDI was characterized by significant shifts of unclassified Clostridiales, Escherichia/Shigella and Veillonella. No peculiar taxa composition correlated with the severity of infection, likely reflecting the role of host-related factors in determining severity.

Environmental Cleaning and Decontamination to Prevent Clostridioides difficile Infection in Health Care Settings: A Systematic Review.

ObjectiveThe aim of this systematic review was to examine the most effective and feasible methods for environmental cleaning and decontamination to prevent Clostridioides difficile infection (CDI) in health care settings.MethodsA systematic search of the databases CINAHL and MEDLINE was conducted from 2008 to 2018 for English language articles with search terms including “Clostridium difficile,” and related medical subject headings, in combination with terms like “disinfection,” “decontamination,” and “no-touch decontamination.”ResultsTwelve studies and 2 systematic reviews were selected for inclusion in this review. The studies were primarily in hospitals (10/12) and used a before-after approach. The studied interventions included cleaning and decontamination with a chlorine-based agent (i.e., bleach; 2 studies), standard cleaning plus the use of hydrogen peroxide decontamination (3 studies), and standard bleach cleaning plus the use of ultraviolet light decontamination (6 studies), and there was 1 study about launderable bed covers. The interventions ranged in frequency, duration, and the area selected for cleaning and decontamination (e.g., all patient rooms versus only CDI patients’ rooms). Studies showed significant reductions in CDI associated with use of bleach (versus quaternary ammonium compound) and hydrogen peroxide decontamination after standard bleach cleaning (versus bleach cleaning alone). Four of 6 studies found significant reductions in CDI after the implementation of ultraviolet light decontamination after standard bleach cleaning.ConclusionsThe studied practices for environmental cleaning and decontamination were associated with significant decreases in facility-level CDI rates in most of the reviewed studies; however, study quality was low. Implementation challenges are worthy of further examination.

Management of Clostridioides difficile infection in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a common diarrheal illness with gastrointestinal and extraintestinal manifestations and complications. The most common infectious complication associated with IBD is Clostridioides difficile infection (CDI). Active IBD predisposes to CDI due to alterations in the gut microbiome. C. difficile is a toxin producing bacterium leading to worsening of underlying IBD, increasing the risk of IBD treatment failure and an increased risk of hospitalization and surgery. Since the symptoms of CDI overlap with those of an IBD flare; it is prudent to recognize that the diagnosis of CDI is challenging and diagnostic tests (nucleic-acid and toxin-based assays) should be interpreted in context of symptoms and test performance. First line treatments for management of CDI in IBD include vancomycin or fidaxomicin. Recurrence prevention strategies should be implemented to mitigate recurrent CDI risk. One needs to monitor IBD disease progression and manage immunosuppression. The risk of recurrent CDI after a primary infection is higher in IBD compared to non-IBD patients. Microbiota restoration therapies are effective to prevent recurrent CDI in IBD patients. This review summarizes the epidemiology, pathophysiology, diagnostic testing, outcomes and management of both CDI and IBD, in CDI complicating IBD.

What is the current state of patient education after Clostridioides difficile infection?

In a survey of hospitals and of patients with Clostridioides difficile infection (CDI), we found that most facilities had educational materials or protocols for education of CDI patients. However, approximately half of CDI patients did not recall receiving education during their admission, and knowledge deficits regarding CDI prevention were common.

Intestinal Microbiota in Elderly Inpatients with Clostridioides difficile Infection.

PurposeThe incidence of Clostridioides difficile infection (CDI) has been reported as 10-fold higher among the elderly population than in young adults. The aim of this study was to compare the targeted bacteria population in the fecal microbiota in two groups of hospitalized elderly, categorized according to CDI and non-CDI.Patient and MethodsIn this case–control study, 84 fecal samples of the 28 patients with CDI and 56 non-CDI patients (>65 years) were studied. C. difficile isolates were characterized by anaerobic culture and multiplex PCR. Quantitative PCR was used to analyze the bacterial elements.ResultsCDI group differed significantly for a prolonged hospital stay, previous surgery, residence in nursing home and exposure to a range of antibiotics including quinolone, clindamycin and cephalosporin. CDI group had significantly fewer members of Bacteroides spp., Clostridium cluster IV, Bifidobacterium spp., Faecalibacterium prausnitzii, and Prevotella spp. in their fecal microbiota than the control group (P < 0.05). The abundances of Akkermansia muciniphila, Lactobacillus spp., Escherichia coli and Klebsiella spp. were higher in group CDI compared with the control group (P < 0.05).ConclusionCDI status is associated with the abundance of some bacterial populations. In this study, an increase in Akkermansia muciniphila, Lactobacillus spp., and Enterobacteriaceae genus was highlighted in CDI patients. A reduction in butyrate-producing bacteria was found in CDI patients. The differences in the composition of fecal microbiota can help to understand how antimicrobial agents impact on gut homeostasis and lead to loss of colonization resistance to C. difficile.

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

Diagnostic and therapy of severe Clostridioides difficile infections in the ICU.

The purpose of the review is to provide all the recent data focusing on the diagnostic and treatment of Clostridioides difficile infection in patients admitted in the ICU. In the ICU, diagnosis remains complicated with a large number of alternative diagnosis. The treatment classically relies on vancomycin but fidaxomicin and fecal microbiota transplantation are now potential solutions in selected indications. Data on ICU-related CDI remain limited and conflicting. To date, there is no unique and simple way to obtain a diagnosis for CDI, the combination of clinical signs and a two-step testing algorithm remains the recommended gold-standard. Two molecules can be proposed for first line treatment: vancomycin and fidaxomicin. Although metronidazole may still be discussed as a treatment option for mild CDI in low-risk patients, its use for ICU-patients does not seem reasonable. Several reports suggest that fecal microbiota transplantation could be discussed, as it is well tolerated and associated with a high rate of clinical cure. CDI is a dynamic and active area of research with new diagnostic techniques, molecules, and management concepts likely changing our approach to this old disease in the near future.

Modeling the potential impact of administering vaccines against Clostridioides difficile infection to individuals in healthcare facilities

BackgroundA vaccine against Clostridioides difficile infection (CDI) is in development. While the vaccine has potential to both directly protect those vaccinated and mitigate transmission by reducing environmental contamination, the impact of the vaccine on C. difficile colonization remains unclear. Consequently, the transmission-reduction effect of the vaccine depends on the contribution of symptomatic CDI to overall transmission of C. difficile. MethodsWe designed a simulation model of CDI among patients in a network of 10 hospitals and nursing homes and calibrated the model using estimates of transmissibility from whole genome sequencing studies that estimated the fraction of CDI attributable to transmission from other CDI patients. We assumed the vaccine reduced the rate of progression to CDI among carriers by 25–95% after completion of a 3-dose vaccine course administered to randomly chosen patients at facility discharge. We simulated the administration of this vaccination campaign and tallied effects over 5 years. ResultsWe estimated 30 times higher infectivity of CDI patients compared to other carriers. Simulations of the vaccination campaign produced an average reduction of 3–16 CDI cases per 1000 vaccinated patients, with 2–11 of those cases prevented among those vaccinated and 1–5 prevented among unvaccinated patients. ConclusionsOur findings demonstrate potential for a vaccine against CDI to reduce transmissions in healthcare facilities, even with no direct effect on carriage susceptibility. The vaccine’s population impact will increase if received by individuals at risk for CDI onset in high-transmission settings.

Risk factors and intestinal microbiota: Clostridioides difficile infection in patients receiving enteral nutrition at Intensive Care Units

BackgroundClostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. In the present study, we assessed the risk factors and intestinal microbiome of patients to better understand the occurrence and development of CDI.MethodsPatients were screened for C. difficile every week after starting EN, and their clinical records were collected for risk factor identification. Fecal samples were analyzed using 16S rRNA sequencing to evaluate the intestinal microbiota.ResultsOverall incidence of CDI was 10.7% (18/168 patients). History of cerebral infarction was significantly associated with CDI occurrence (OR, 9.759; 95% CI, 2.140–44.498), and treatment with metronidazole was identified to be protective (OR, 0.287; 95% CI, 0.091–0.902). Patients with EN had lower bacterial richness and diversity, accompanied by a remarkable decrease in the abundance of Bacteroides, Prevotella_9, Ruminococcaceae, and Lachnospiraceae. Of these patients, acquisition of C. difficile resulted in a transient increase in microbial diversity, along with consistent alterations in the proportion of some bacterial taxa, especially Ruminococcaceae and Lachnospiraceae. Upon initiation of EN, patients who were positive for C. difficile later showed an enhanced load of Bacteroides, which was negatively correlated with the abundance of C. difficile when CDI developed.ConclusionICU patients receiving EN have a high prevalence of CDI and a fragile intestinal microbial environment. History of cerebral infarction and prior treatment with metronidazole are considered as vital risk and protective factors, respectively. We propose that the emergence of CDI could cause a protective alteration of the intestinal microbiota. Additionally, Bacteroides loads seem to be closely related to the occurrence and development of CDI.

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis

Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P= .003), had pseudomembranes (22.2% vs 0; P= .018), and underwent FMT as inpatients (45.5% vs 19%; P= .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P= .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P= .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.