Clostridium Difficile Colonization Research Articles

72 Effect of In-feed fecal microbiota transplant on growth performance and gut microbiota dynamics of piglet subjected to post-weaning stress

Abstract Weaning is one of the most stressful events for piglets, due to diet change from sow milk to grain-based feed. This diet change causes turnover of the gut microbial which can allow proliferation of pathogens leading to diarrhea. Antibiotics are administered to treat or prevent post-weaning diarrhea (PWD). Increased occurrence of antimicrobial resistance has increased incentives to develop viable antibiotic alternatives. PWD is most often caused by enterotoxigenic Escherichia coli. Similarly, in humans, severe diarrhea can be caused by Clostridium difficile colonization. Use of fecal microbiota transplants (FMT) has been shown to resolve C. difficile-induced diarrhea in 80 to 90% of human cases which may suggest FMT as a potential therapeutic option for post weaning diarrhea. We previously have shown that in feed fecal microbiota transplant (FMT) improved body weight (BW) gain in newly weaned piglets but it is not clear if this benefit will be replicated in piglets subjected to weaning stress. We hypothesize that FMT (in-feed) will increase colonization efficiency, improve growth performance and reduce diarrhea incidence compared with control in piglets subjected to post weaning stress. The objective of this study was to determine the effect of In-feed FMT of diarrhea index, growth performance and gut microbiota dynamics. Piglets (n = 240) subjected to physiological and transport weaning stress were allotted to 5 treatments: In-feed FMT (FMT1), doubles dose of In-feed FMT1 (FMT2), Oral gavage (FMT3), Antibiotic (positive control), and no supplementation (negative control). The donor material was screened for enterotoxigenic E. coli (F18 and F4). FMT was carried out for 14 d. Diarrhea index was observed for the first 14 d and animal BW, and fecal microbiota was collected by rectal swab on d 0, 3, 5, 7, 14, 21, 28 and 32 for analysis of microbiota composition. DNA was extracted from fecal samples and 16S rRNA gene libraries (V4 region) were prepared for bacterial community analysis. Data were analyzed with one-way ANOVA in R. Only positive control had significantly decrease in diarrhea index and significant increase BW gain on d 14, 21, and 28 (P < 0.05) but there was no effect of FMT (P > 0.05). In conclusion, antibiotics but not FMT was efficient in alleviating the negative performance effect in piglets subjected to post-weaning stress.

691. Association between Clostridioides difficile Colonization, Rectal Swab NAAT Positivity, and Environmental Contamination

Abstract Background Clostridioides difficile (CD) colonization is common among hospitalized patients. Screening for toxigenic CD (TCD) colonization with rectal swab nucleic acid amplification tests (NAAT) may identify people at risk for CDI and help prevent onward TCD transmission, especially in immunocompromised patients with long hospitalizations. The study objective was to test whether rectal swab NAAT could detect TCD colonized patients and whether NAAT results identify patients that contribute to environmental contamination. Methods This was a prospective cohort study on two BMT/Leukemia units. Stool specimens, rectal swabs, and environmental swabs (bedrail, room sink, keyboard) were collected from patients at admission and weekly and cultured semi-quantitatively for TCD. NAAT (Cepheid) was performed on rectal swabs (eSwabs; Copan Diagnostics). The relationship between stool TCD concentration, NAAT Ct, and a positive environmental culture was evaluated using univariate logistic regression. Bleach was used for daily and terminal discharge cleaning of all rooms. Toxigenicity was determined by detection of tcdA or tcdB by whole genome sequencing (WGS). Results From January 2019 - July 2019, 659 stool specimens and 495 rectal swabs were collected from 384 patients. Specimens from 554 patient-days were cultured and 126 (23%) were positive. Of those, 88 (70%) were TCD. 21 of 987 (2%) environmental swabs were TCD positive; 18 (86%) were from bedrails. Among 61 unique patient calendar days with paired rectal swab NAAT and stool culture results (paired samples), overall sensitivity of rectal swab NAAT to detect toxigenic CD colonization compared to culture was 44%, with 4/16 (25%) of people colonized with > 0 - < 10,000 CFU/g of TCD and 7/9 (78%) with ≥ 10,000 CFU/g TCD (Figure 1). There was no relationship between stool culture or rectal swab NAAT result and risk of a positive environmental swab (Figure 2). Figure 1. Toxigenic C. difficile semi-quantitative culture and rectal swab NAAT on paired patient-day of specimen collection (N=61 patient-days) Figure 2. Toxigenic C. difficile semi-quantitative stool and rectal swab NAAT results and environmental contamination by paired patient-day of specimen collection Conclusion Rectal swab NAAT may not be sufficiently sensitive to screen for TCD colonization that contributes to environmental contamination. Disclosures Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support

Clostridioides difficile Infections among Pediatric Patients Hospitalized at an Oncology Department of a Tertiary Hospital in Poland.

Background and Objectives: Gastrointestinal tract infections caused by Clostridioides difficile bacteria are diagnosed in pediatric patients with increasing frequency. Children treated at pediatric units are a group of patients at high risk of this infection; therefore, appropriate differential diagnostics and an individual approach to every case are of particular importance. The goal of the study was to assess the clinical parameters of patients with a confirmed CD infection and colonization. Materials and Methods: Every positive case was subjected to a retrospective analysis based on medical history and an infection notification note. Results: Positive results were obtained for 30 patients, among whom the results of 18 patients were considered to justify the diagnosis of an infection. In the remaining patients, treatment was not initiated in only three cases. Cases were detected where treatment was initiated despite the lack of sufficient clinical evidence. Conclusions: This study demonstrates that there are many factors that result in a high risk of the occurrence of CDI in oncology patients, such as antibiotic therapy, multiple hospitalizations, and myelosuppression.

Interventional Antibiotic Treatment Replacing Antibiotic Prophylaxis during Allogeneic Hematopoietic Stem Cell Transplantation Is Safe and Feasible: A Single-Center Analysis

Background: Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of infection-related mortality during the pre-engraftment period. Systemic antibiotic prophylaxis (SAP) is widely used during the period of neutropenia but is associated with disruption of the intestinal microbiome, an increased risk of Clostridium difficile infection (CDI) and colonization with multi-drug resistant (MDR) bacteria. Aims: We retrospectively assessed the safety and efficacy of a change in our center policy from SAP to an exclusively interventional antibiotic treatment (IAT) in adult patients undergoing allogeneic HSCT. Outcome measures were overall survival (OS) and non-relapse mortality (NRM) at 3 years, antibiotic administration, incidence of blood-stream infections (BSI) and incidence and severity of acute and chronic graft-versus-host disease (GVHD). Methods: Cefotaxime was used as standard of care prophylaxis during neutropenia after HSCT prior to January 2018. After a 12 months transition time during which both strategies were employed in parallel, SAP was replaced by an IAT strategy with meropenem being administered immediately by nursing staff in case of neutropenic fever or any other signs of infection, and subsequently deescalated to piperacillin/tazobactam (pip/taz) when appropriate. We compared 67 consecutive patients undergoing HSCT in 2017, all of whom received antibiotic prophylaxis (SAP cohort) with all patients in 2019 comprising the IAT cohort (n=68). Use of antibiotics is reported as number of daily doses per 100 care days (DDD/100CD) until discharge after HSCT. Results: Patient characteristics are summarized in table 1. Median age was 56 years, 82% of patients were grafted with peripheral blood stem cells (PBSC) for acute leukemia (74%) from a matched unrelated or related donor (MUD, 61%; MRD 17%). Patient characteristics were well balanced between the SAP and IAT cohorts, except those patients transplanted in 2019 were more likely to have an HCT-CI ≥ 3 (56% vs 36%, p=0.025) and receive reduced-intensity conditioning (62% vs 40%, p=0.025). In the SAP and IAT cohort, neutropenic fever was observed in 46% and 62% of patients (p=0.085). However, the cumulative incidence (CI) of BSI by day +100 post-HSCT was significantly higher in the IAT vs SAP cohort (40% vs 13%, p<0.001), which did not result in more patients admitted to the intensive care unit (13% vs 6%, p=ns) and did not translate into a higher CI of NRM at 3 years (10% vs 9%, p=ns). With a median follow-up of 1052 days, 3-year OS was 70% and 69% for the SAP and IAT cohort, resp. (p=ns, figure 1). CI of acute GVHD grade II-IV or chronic GVHD of any grade at 3 years was 34% (p=ns) and 45% (p=ns), resp., resulting in identical survival free of acute GVHD grade III-IV, chronic GVHD requiring systemic immunosuppressive therapy and relapse-free survival (GRFS) of 36% (p=ns) in both groups. We observed a tendency to a higher CI of severe chronic GVHD in the SAP cohort (27% vs 13%, p=0.08). There was no significant difference between the two cohorts in terms of newly detected colonization with MDR bacteria during conditioning and after HSCT (VRE 17%; ESBL 5%; 3/4 MRGN 5%; MRSA 0%) and the incidence of CDI was likewise equal in both cohorts (13%, p=ns). Compared to SAP, IAT resulted in significantly fewer days of antibiotic therapy (24 vs 18, p<0.001) and accordingly less administration of cefotaxime (12.8 vs 3.8 DDD/100CD), teicoplanin (26.2 vs 6.3 DDD/100CD), vancomycin (11.5 vs 8.3 DDD/100CD) and meropenem (23.1 vs 16.7 DDD/100CD). Solely use of pip/taz increased (14.3 vs 23.6 DDD/100CD), while the amount of imipenem remained unchanged (7.6 versus 7.8 DDD/100CD). Thus, we observed a significant 40% reduction of the median antibiotic consumption (p=0.0312) in 2019. In the multivariate analysis, only age > 60 years and a high or very high disease risk index were identified as negative prognostic factor for OS. Conclusion/Summary: Our single center experience in conducting HSCT without antibiotic prophylaxis but with strict guidelines for prompt antibiotic intervention demonstrated no disadvantage in OS and NRM, despite a higher CI of BSI. IAT resulted in considerably less consumption of cefotaxime, but also carbapenem and glycopeptide antibiotics. We conclude that the proposed procedure of IAT replacing SAP is safe and feasible. Larger patient numbers are needed to confirm a possible benefit of IAT on GVHD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improving Stewardship of Clostridioides difficile Testing with EMR and Provider Phone Calls.

IntroductionModern laboratory techniques cannot differentiate between Clostridium difficile colonization and infection; therefore, testing must be indicated clinically. To reduce hospital-onset of C. difficile infections (HO-CDI), Ascension Via Christi Hospitals (AVCH) in Wichita intervened in three stages by introducing: 1) a C. diflcile testing algorithm; 2) an electronic medical record (EMR)-based decision support system to enforce said algorithm; and 3) phone calls from the infection prevention department to providers to discontinue tests not collected within 24 hours of the order. The goal of this study was to determine if these interventions improved the HO-CDI rate.MethodsAt AVCH, the three study periods were compared: baseline with algorithm training only, the EMR intervention, and the EMR intervention with additional phone calls (EMR with phone calls). Data were abstracted from the hospital EMR.ResultsA total of 311 charts were reviewed. Adherence to the algorithm increased from 34% at baseline to 52% after the EMR intervention (p = 0.010). During the EMR with phone calls period, more tests were discontinued (87%; n = 39) compared to baseline (54%; n = 15) and EMR (54%; n = 15; p = 0.003). The HO-CDI rate ranged from 8.5 cases per 10,000 patient-days at baseline, to 7.9 during EMR, to 4.0 during EMR with phone calls (p = 0.007).ConclusionsThe EMR and EMR with phone call interventions were associated with a significant decrease in the HO-CDI rate and an increase in provider adherence to the algorithm.

754. A Two-step Testing Algorithm for Hospital-onset Clostridioides difficile Infection (CDI) Reduces Prescribing of C. difficile (CD) Therapy but Its Ability to Guide Treatment Decisions Remains Unclear

BackgroundDetermining true CDI versus CD colonization through CD testing is a continuing challenge. A previously introduced decision support tool at UVA Health significantly reduced inappropriate testing without adverse outcomes. More recently, our methodology changed from nucleic acid amplification test (NAAT) alone to an initial NAAT followed by ELISA for toxin to improve specificity. The purpose of this analysis was to assess provider interpretation of test results, using targeted CD therapy as a surrogate.MethodsThis single-center, retrospective study evaluated all patients with a positive NAAT (Cepheid Xpert® C. difficile) on day 4 or later of hospitalization following 2-step algorithm implementation from Feb 2020 through Feb 2021. Toxin negative (TOX-) test results (C. DIFF QUIK CHEK COMPLETE®) were accompanied by a comment that discordance may represent colonization or CDI and to consider ID consult. The proportion of toxin positive (TOX+) versus TOX- patients receiving ≥ 1 dose of CD therapy served as the primary outcome with partial courses considered < 10 days. Clinical outcomes were also compared.ResultsNinety patients with NAAT+ results were included, of whom 58 (64%) were TOX-. Thirty-two (100%) TOX+ (median days of therapy [IQR] = 14 [11-17]) versus 51 (88%) TOX- patients (median days of therapy [IQR] = 11 [7-14]) received CD therapy (p=0.04). Treatment decisions were guided by ID physicians for 32 (63%) TOX- patients; ID recommendations to discontinue CD therapy were followed in 2 out of 9 (22%) cases. TOX- patients received partial therapy due to patient death (n=5), presumptive colonization (n=3), and provider error (n=1). Of TOX- patients receiving partial or no treatment, there were no CDI-related adverse outcomes during the admission. CDI-related colectomy occurred in 2 (6%) and 1 (2%) TOX+ and TOX- patients, respectively. Five in-hospital deaths with CDI as a contributing factor occurred in the TOX+ group. ConclusionAdoption of a 2-step NAAT plus toxin testing algorithm for hospital-onset CDI reduced the frequency with which TOX- patients received CD therapy but the vast majority were still treated. Most providers considered a positive NAAT indicative of CDI, regardless of TOX status. Disclosures All Authors: No reported disclosures

71. Diagnostic Stewardship of Clostridioides difficile Testing

Background C. difficile (CD) testing is frequently ordered inappropriately. Highly sensitive polymerase chain reaction (PCR) tests can detect CD colonization leading to misdiagnosis. Providers often overlook other causes of diarrhea, notably laxatives. To improve diagnostic stewardship, our hospital introduced an electronic medical record (EMR)-based order set (OS). MethodsIn a 926-bed, teaching hospital, we conducted a 3-step intervention to improve CD diagnostic stewardship. (1) A retrospective analysis of CD orders before and after OS implementation was done to assess its impact on inappropriate orders. The OS included two questions: (a) Did patient have ≥ 3 loose bowel movements in past 24 hours? and (b) No laxatives in past 24 hours? An appropriate order was defined if “yes” to both questions. It was still appropriate if “no” to either question but ≥ 2 unexplained following features: fever > 100.4 F, abdominal pain, megacolon, ileus or leukocytosis > 11,000 cells/mm3 in prior day. (2) After implementation of OS, house staff compliance with OS was surveyed via email. (3) Rationale for inappropriate orders was discussed with providers.ResultsOf 238 patients in retrospective analysis, 44% were ≥ 65 years and 37% had other potential causes of diarrhea. Common clinical features were leukocytosis (40%) and fever (31%). There was no significant difference in inappropriate testing: pre-OS 27/99 (27%) vs post-OS 44/139 (32%) (p=0.47). Of 43 house officers who participated in the survey, 75% indicated they over rode the OS. When asked to provide rationale of inappropriate CD testing, providers acknowledged inappropriate ordering but did not want to miss a CD diagnosis and frequently overlooked other causes of diarrhea.ConclusionAppropriate CD testing relies on providers’ appreciation of a clinical picture consistent with CD infection, confirmation of clinically significant diarrhea, and consideration of other causes of diarrhea. Providers order inappropriate tests, not due to lack of knowledge, but likely fear of missing diagnosis and overlooking other causes of diarrhea.Disclosures All Authors: No reported disclosures

Clostridium difficile Colonization Before and After Hospitalization in Children.

Background:Beginning in the early 2000s, Clostridium difficile infection has become a major health problem in the United States, Canada, and in most European countries and has not only increased in incidence but also the severity. There are 2 conditions for the development of C. difficile infection: disruption of the normal gastrointestinal flora, and exogenous ingestion of the microorganism. We aimed to study C. difficile colonization in hospitalized children. We identified 2 issues: (1) the relationship between risks before hospital admission and colonization on the first day of hospitalization and (2) the effect of the factors that patients are exposed to during hospitalization on the colonization status at discharge.Methods:Patients aged between 2 and 18 years who were hospitalized with various diagnoses were included in this study. C. difficile toxin A/B was investigated in the stool samples taken on the admission and discharge days.Results:One hundred six patients were included in the study, of whom 24.5% and 48.1% of hemato-oncology patients were positive for C. difficile toxin A/B. Antibiotic usage within 1 month preceding hospitalization and the presence of underlying disease impact the C. difficile colonization status on the first day of hospitalization.Conclusion:Toxigenic C. difficile colonization prevalence is high in hospitalized children, especially in the hemato-oncology patient group.

Epidemiology and risk factors for hospital acquired Clostridium difficile infection and colonization in emergency intensive care unit of a general hospital in Shanghai

To investigate the clinical features, risk factors and prognosis of Clostridium difficile infection/colonization (CDI/CDC) in emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, then provides theoretical basis for clinical treatment. A retrospective case-control study was conducted. The data of EICU patients admitted to Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2016 to June 2020 were collected. Taking the CDI/CDC patients as research objects [Clostridium difficile (CD) positive group] and the CD negative patients with the same gender and age difference less than 5 years who were admitted to the hospital during the same period as the control (CD negative group). Demographic information, risk factors, prognosis and stool samples were collected. Single factor analysis and binary Logistic regression were used to analyze the CD positive infection rate, risk factors, and hospital death of patients with different clinical characteristics. About 487 patients in EICU were included, 76 cases were taken into CD positive group, CD positive rate was 15.6%, including CDI 11 cases, CDC 65 cases. Among the CD positive group, all of the cases used proton pump inhibitor (PPI), and 75 cases used at least one antibiotic. Seventy-six CD negative patients with or without diarrhea (CD negative group) were included in this study. Among them, 75 patients used PPI and 74 patients used at least one antibiotic. Univariate analysis showed that acute physiology and chronic health evaluation II (APACHE II), duration of hospitalization, and carbapenem use were the risk factors for CDI/CDC. There were significant differences in the above indicators between CD positive group and CD negative group [APACHE II: 18.0 (12.2, 25.8) vs. 10.0 (7.0, 14.0), duration of hospitalization (days): 46.0 (30.5, 72.5) vs. 18.5 (9.2, 37.0), proportion of carbapenems: 81.6% (62/76) vs. 64.5% (49/76), all P < 0.05]. Binary Logistic analysis regression analysis showed that APACHE II score [odds ratio (OR) = 0.802, 95% confidence interval (95%CI) was 0.730-0.882, P < 0.01] and duration of hospitalization (OR = 0.960, 95%CI was 0.942-0.978, P < 0.01) were independent risk factors for CDI/CDC. There was no difference in overall mortality between the CD positive group and CD negative group [27.6% (21/76) vs. 38.2% (29/76), P = 0.167]. Critically ill patients in EICU routinely use PPI and antibiotics, and the use of antibiotics does not affect the CD positive rate. The independent risk factors of CDI/CDC are the APACHE II score and the duration of hospitalization, but fecal CD positive has no obvious influence on death.

Clinical manifestations of pseudomembranous colitis

Pseudomembranous colitis is a pathological condition in which there is damage to the mucous membrane of the large intestine with focal or diffuse fibrin depositions resulting from exposure to factors of the pathogenicity of Clostridium difficile. This disease has become quite widespread in recent years. The widespread and not always properly controlled prescription of antibiotics can lead to the development of a serious complication caused by this pathogen. The pathological condition develops against the background or after the end of the ongoing antibiotic therapy; its initial manifestation is antibiotic-associated diarrhea (AAD). Most often, this condition is diagnosed in postoperative patients against the background of a general decrease in immunity, as well as as a result of prolonged and uncontrolled intake of antibiotics. It has been proven that the frequency of Clostridium difficile colonization increases sharply during hospitalization, thus, this infection was referred to hospital ones. The main clinical manifestation of pseudomembranous colitis is diarrhea; stool can become more frequent, up to 5-7 times a day, while feces are scanty and not abundant. In addition to diarrhea, abdominal pain and flatulence may occur. The diagnosis is established on the basis of the fact of increased stool within two or more days for 8 weeks after taking antibiotics confirmed by the patient.

Factors Associated with Clostridioides (Clostridium) Difficile Infection and Colonization: Ongoing Prospective Cohort Study in a French University Hospital.

Introduction: Clostridioides (Clostridium) difficile can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. C. difficile, the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from C. difficile infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by C. difficile and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for C. difficile testing are obtained on admission, every 3–5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l’Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.

Clostridium difficile infection and its susceptibility factors in children with inflammatory bowel disease

OBJECTIVE To investigate the incidence rates of Clostridium difficile colonization and Clostridium difficile infection (CDI) in children with inflammatory bowel disease (IBD) and the susceptibility factors for CDI in children with IBD. METHODS A total of 62 children diagnosed with IBD were enrolled as the IBD group. Forty-two children who attended the hospital due to persistent or chronic diarrhea and were excluded from IBD were enrolled as the non-IBD group. The incidence rate of CDI was compared between the two groups. According to the presence or absence of CDI, the IBD group was subdivided into two groups:IBD+CDI (n=12) and non-CDI IBD (n=50), and the clinical data were collected from the two groups to analyze the susceptibility factors for CDI. RESULTS The IBD group had a significantly higher incidence rate of CDI[19% (12/62) vs 2% (1/42); P < 0.05] than the non-IBD group (P < 0.05). Compared with the non-CDI IBD group, the IBD+CDI group had a significantly longer disease course (P < 0.05), and a significantly higher proportion of children with fever, diarrhea, or abdominal pain (P < 0.05). The IBD+CDI group had significantly higher activity indices of pediatric Crohn's disease, C-reactive protein levels and erythrocyte sedimentation rate than the non-CDI IBD group (P < 0.05). The univariate analysis showed that compared with the non-CDI IBD group, the IBD+CDI group had a significantly higher proportion of children with moderate-to-severe disease, use of glucocorticoids, or treatment with broad-spectrum antibiotics for more than 14 days before diagnosis (P < 0.05). CONCLUSIONS The children with IBD have a higher incidence of CDI than those without IBD. Severe disease conditions and use of broad-spectrum antibiotics or glucocorticoids may be associated with an increased incidence of CDI in children with IBD.

Toxigenic Clostridium Difficile Colonization in Patients with Hematologic Malignancies Admitted to the Hospital for Chemotherapy or Hematopoietic Cell Transplantation

Background: Clostridium difficile (CD) is an important cause of infectious diarrhea in patients with hematologic malignancies (HM) admitted to the hospital for chemotherapy or hematopoietic cell transplantation (HM-HCT patients). These patients are at increased risk of developing Clostridium difficile infection (CDI) compared to non-oncology patients, and they are more likely to suffer adverse outcomes from the infection. Asymptomatic colonization of patients with CD is known to precede infection. However, the reported prevalence of asymptomatic colonization varies widely between studies. The primary objective of this study was to define the prevalence of toxigenic CD colonization in patients with hematologic malignancies who were admitted to the hospital for scheduled chemotherapy or hematopoietic cell transplantation (HCT). The secondary objective was to determine what microbiology tests are accurate in detecting CD colonization compared to the gold standard of toxigenic culture.Method: We performed a prospective cohort study of HM-HCT patients at our institution. Patients were included if they were age 18 years or older and scheduled for elective admission for chemotherapy or HCT (including both autologous and allogeneic HCT). Patients were excluded if they had diarrhea due to CDI in the past 30 days; if they had diarrhea of unknown etiology; if they were admitted on an unscheduled basis for treatment of acute illness; or if their anticipated length of stay was less than 72 hours. At the time of hospital admission for scheduled chemotherapy or HCT, a stool specimen was collected from each patient in a clean sterile collection vial. All samples were freshly collected and sent to the microbiology laboratory for processing. The stool samples were tested with six different methods: Simplexa™ C. difficile PCR Universal Direct Kit, Cepheid Xpert® PCR C.difficileCD/Epi (Xpert CD/Epi), C. diff Quik Chek Complete® GDH, C. diff Quik Chek Complete® Toxin A/B, LEUKO EZ VUE® ELISA test, and toxigenic culture. Toxigenic culture was used as the reference method. Baseline characteristics of those who tested positive versus negative were described using summary statistics, and univariable logistic regression analysis was used to identify risk factors for CD colonization. Sensitivity and specificity with 95% confidence interval for five tests were estimated.Results: A total of 114 patients were recruited for participation between April 2016 and November 2016. Thirteen patients either withdrew consent or did not provide a stool sample, so the final CD analysis included 101 patients. The demographic and clinical characteristics of the included patients are presented in Table 1. The prevalence of toxigenic CD colonization as determined by toxigenic culture was 13% (14/101, [95% CI: 8-22%]). The Cepheid Xpert PCR CD/Epi showed the highest sensitivity. The sensitivity and specificity of the different testing methods are shown in Table 2. The median (range) length of hospital stay was 13 (2-57) days. Among the 14 patients who tested positive by toxigenic culture, only 1 patient (7%) patient developed CDI during his hospitalization, and his stool tested positive by Cepheid Xpert PCR CD/Epi prior to the development of CDI. Univariable logistic regression analysis did not identify any risk factors for CD colonization including prior CDI, antibiotic use in the past 30 days, or treatment with proton pump inhibitors.Conclusions: Toxigenic CD colonization was high in our cohort of patients, but the majority of patients who were colonized with toxigenic CD did not develop CDI while hospitalized. There were no identifiable risk factors for CD colonization. The most sensitive test for identifying toxigenic CD colonization was the Cepheid Xpert PCR CD/Epi test. Our findings suggest that the Cepheid Xpert PCR CD/Epi test could be used to screen for toxigenic CD colonization in patients admitted for scheduled chemotherapy or HCT. However, the costs and benefits of such an approach warrant further investigation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Trends in Clostridioides difficile diagnosis before and after a change in testing algorithm

Clostridioides difficile (Clostridium difficile) (CD) infection remains a challenging diagnosis in hospitalized patients given the myriad of testing procedures and array of alternative causes for diarrhea. We identified 100 consecutive inpatients with positive CD testing in a single tertiary center before and after changing from nucleic acid amplification testing (NAAT) alone to a two-step algorithm involving Glutamate Dehydrogenase enzyme immunoassays (GDHEIA) followed by an enzyme immunoassay for CD toxins (EIA). Detailed clinical information was obtained retrospectively to assess for risk factors, clinical features, and treatment outcomes to correlate test results with clinical cases. We demonstrate that using a 2-step testing algorithm identifies patients with a consistent clinical illness for CD disease significantly more often than nucleic acid amplification testing alone without an increase in cases of severe CD disease. Our data suggest that NAAT alone results in an increase in unnecessary treatment of CD colonization.

Fulminant Clostridium Difficile colitis after ileostomy reversal: Case Report and Review of Literature

Introduction: Clostridium Difficile infection (CDI) following restoration of intestinal continuity is uncommon and may progress to fulminant colitis. Fulminant CDI is associated with significant morbidity and mortality. In an unwell patient without clear evidence of an anastomotic leak, surgeons should be aware of the possibility of CDI and institute appropriate management. Presentation of Case: We report the case of a 71- year-old man, who presented for an elective loop ileostomy reversal after an ultra-low anterior resection for a low rectal cancer eight months prior. The patient deteriorated clinically on post-operative day (POD) 4 and by POD 5 was in septic shock with multi-organ failure. A relook laparotomy confirmed no anastomotic leak and a flexible sigmoidoscopy revealed typical appearance of pseudomembranous colitis. The patient continued to deteriorate in the intensive care unit despite oral and rectal Vancomycin. An abdominal computed tomography (CT)1 on POD 9 demonstrated severe pancolitis and enteritis necessitating surgical intervention. He underwent an emergency subtotal colectomy with an end ileostomy after failing medical management. Discussion: Many factors have been shown to increase the incidence of Clostridium difficile colonization in the colon including recent hospitalization, antibiotic use, and length of defunctioning beyond six months. The presence of risk factors associated with an increase in CDI such as proton pump inhibitor use, steroid use or immunosuppression and advanced age may allow surgeons to predict high risk patients. Conclusion: Although rare, fulminant CDI following reversal of ileostomy is a potentially fatal condition. Surgeons should be aware of the risk factors predisposing patients to CDI particularly in a patient with an acute abdomen without clear evidence of an anastomotic leak.

Prevention of Clostridium difficile Infection and Associated Diarrhea: An Unsolved Problem

For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen.

S0179 Role of Oral Vancomycin Prophylaxis in Preventing Recurrent Clostridioides difficile Infection in Hospitalized Patients Requiring Antibiotics: A Randomized Controlled Trial

INTRODUCTION: Clostridioides Difficile Infection (CDI) is a common health-care associated infection causing significant morbidity and mortality. There has been a dramatic increase in the incidence and severity of CDI due to emergence of NAP1 strain, use of broad-spectrum antibiotics, PPIs, and prolonged hospitalization with 1-3 month recurrence rates of around 25%. There are currently no evidence-based guidelines describing the role of oral vancomycin prophylaxis (OVP) to prevent recurrent CDI, thus accounting for the wide variation in practice. We aimed to evaluate the efficacy of OVP in reducing recurrence of CDI in hospitalized patients receiving antibiotics with a prior history of CDI, via a single-center randomized controlled trial. METHODS: Study was commenced following IRB approval in March 2018. Primary objective was to evaluate the efficacy of OVP in reducing recurrence of CDI in in-patients with prior CDI and receiving antibiotics. Secondary goal was to determine the differences in rate of recurrent CDI stratified by various CD inducers, dose of OVP, NAP1 strain, concurrent PPI use, time interval from prior CDI and pre-existing risk factors. We randomized in-patients receiving antibiotics, with prior CDI, to one of three arms in a 1:1:1 ratio following inclusion and exclusion criteria. Group A, B and C received oral vancomycin 125 mg daily, 125 mg twice-daily and no oral vancomycin respectively. OVP was given until the completion of antibiotics for primary infection. Patients were evaluated 12 weeks following completion of OVP using a standardized questionnaire. RESULTS: 109 patients were randomized with zero rate of recurrence in all groups. Secondary objectives could not be determined due to null recurrence. Death due to causes unrelated to CDI was noted in 10.1% of the entire cohort, of which 5.1% occurred in treatment groups while 5% occurred in control group. Three or more episodes of diarrhea was reported by 18.2% patients during follow-up; 12.2% were among treatment groups. CONCLUSION: Our results indicate no difference in recurrence rates between treatment and control groups. Based on our data, lack of recurrent CDI in our facility could be related to the rigorous antibiotic stewardship program initiated prior to the commencement of this study, low incidence of NAP-1 strain in our study cohort, as well as a new immunoassay for toxin detection which distinguishes between CD colonization from active CDI.

A Spore‐Forming Probiotic Supplement Improves the Intestinal Immune Response and Protects the Intestinal Health During Recurrent Clostridioides difficile Colonization in Mice

Around 15%-30% of patients develop recurrent Clostridioides difficile infection (CDI) as conventional therapies disrupt protective gut microbiota. We tested if supplementation with a spore-forming probiotic would protect intestinal health in a mouse model of recurrent CD colonization. Methods: Female CF-1 mice were exposed to CD spores (4-log10 colony-forming units/10 μL) and then randomly assigned to receive either saline (CD-S) or probiotic (CD-PRO). Control mice received only saline (control). Following confirmation of initial CD colonization, mice were treated with vancomycin (10 days). After 5 days, mice recolonized with CD were treated again with vancomycin (10 days) and euthanized 5 days later. Fecal samples were collected at select time points for bacterial analysis. Following euthanasia, blood samples, cecum contents, and the intestine were collected for analysis. Probiotic supplementation mitigated the antibiotic-induced changes in cecum weight (P < .001). Probiotic-supplemented mice had increased messenger RNA expression of several immune parameters, accompanied by lower serum iron levels compared with CD-S mice (P < .05). Lower expressions of TNF α and calprotectin (P ≤ .05) were observed in CD-PRO mice compared with CD-S. The probiotics also supported the expression of intestinal tight junction proteins, which were diminished in the proximal colon of CD-S mice (P < .05). Mice supplemented with targeted spore-forming probiotics exhibited improved immune responses and nutrition immunity properties, which were linked with less inflammation and enhanced intestinal barrier proteins during recurrent CD colonization.

Some simple rules for estimating reproduction numbers in the presence of reservoir exposure or imported cases

For many diseases, the basic reproduction number (R0) is a threshold parameter for disease extinction or survival in isolated populations. However no human population is fully isolated from other human or animal populations. We use compartmental models to derive simple rules for the basic reproduction number in populations where an endemic disease is sustained by a combination of local transmission within the population and exposure from some other source: either a reservoir exposure or imported cases. We introduce the idea of a reservoir-driven or importation-driven disease: diseases that would become extinct in the population of interest without reservoir exposure or imported cases (since R0<1), but nevertheless may be sufficiently transmissible that many or most infections are acquired from humans in that population. We show that in the simplest case, R0<1 if and only if the proportion of infections acquired from the external source exceeds the disease prevalence and explore how population heterogeneity and the interactions of multiple strains affect this rule. We apply these rules in two case studies of Clostridium difficile infection and colonisation: C. difficile in the hospital setting accounting for imported cases, and C. difficile in the general human population accounting for exposure to animal reservoirs. We demonstrate that even the hospital-adapted, highly-transmissible NAP1/RT027 strain of C. difficile had a reproduction number <1 in a landmark study of hospitalised patients and therefore was sustained by colonised and infected admissions to the study hospital. We argue that C. difficile should be considered reservoir-driven if as little as 13.0% of transmission can be attributed to animal reservoirs.

Diarrhoeal events can trigger long-term Clostridium difficile colonization with recurrent blooms.

Although Clostridium difficile is widely considered an antibiotic- and hospital-associated pathogen, recent evidence indicates that this is an insufficient depiction of the risks and reservoirs. A common thread that links all major risk factors of infection is their association with gastrointestinal disturbances, but this relationship to C. difficile colonization has never been tested directly. Here, we show that disturbances caused by diarrhoeal events trigger susceptibility to C. difficile colonization. Using survey data of the human gut microbiome, we detected C. difficile colonization and blooms in people recovering from food poisoning and Vibrio cholerae infections. Carriers remained colonized for year-long time scales and experienced highly variable patterns of C. difficile abundance, where increased shedding over short periods of 1-2 d interrupted week-long periods in which C. difficile was undetectable. Given that short shedding events were often linked to gastrointestinal disturbances, our results help explain why C. difficile is frequently detected as a co-infecting pathogen in patients with diarrhoea. To directly test the impact of diarrhoea on susceptibility to colonization, we developed a mouse model of variable disturbance intensity, which allowed us to monitor colonization in the absence of disease. As mice exposed to avirulent C. difficile spores ingested increasing quantities of laxatives, more individuals experienced C. difficile blooms. Our results indicate that the likelihood of colonization is highest in the days immediately following acute disturbances, suggesting that this could be an important window during which transmission could be interrupted and the incidence of infection lowered.