bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Oral Vancomycin, Oral Metronidazole, or IV Metronidazole Prophylaxis at Reducing the Risk of Clostridium difficile Recurrence
Authors: O’Connell Matthew , Slish Judianne , Shelly Mark 
Published: October 2017

Abstract

Background
Secondary prophylaxis (SP) for Clostridium difficile infection (CDI) with oral vancomycin or oral/IV metronidazole when initiating antibiotics is common, though few studies are available to support this practice. The purpose of this study was to assess the efficacy of prophylaxis within a year of index CDI.

Methods
This retrospective chart review looks at subsequent courses of antibiotics and CDI in patients with initial positive CDI testing in 2013–16. A positive CDI test within 90 days of antibiotics was a recurrence. The use of antibiotics for SP was noted, along with other factors associated with CDI relapse. Non-parametric and exact tests were used for univariate analysis. These variables were included in a multivariate proportional hazards model.

Results
We found 597 antibiotic episodes in 230 patients. 130 episodes (21.8%) received SP. The difference of recurrence rates with and without antibiotics, 9.2 % vs 10.7%, was not statistically significant. No difference was seen when metronidazole was used, but vancomycin SP reduced the rate to 7.5% (6/80, P = 0.45). Probiotics were associated with a higher rate of recurrence (16.7 vs. 8.9%, P = 0.025). Proton pump inhibitors were also associated with a slightly higher rate of CDI recurrence (13.0% vs. 8.4%). The rate of relapse fell significantly with increasing time since the index case of CDI by logistic regression (P = 0.011). In multivariate regression, relapse was associated with shorter time from index CDI, shorter durations of antibiotics, and the use of probiotics.

Conclusion
This retrospective study does not support the routine use of metronidazole in subsequent antibiotic courses following CDI. The use of probiotics paradoxically increased the rate of CDI relapse in this study. The limitations of this retrospective study do not eliminate the possibility of utility of vancomycin as prophylaxis, but this requires further evaluation.

Disclosures
All authors: No reported disclosures.
Tetracyclines are Associated with a Reduced Risk of Clostridium difficile Infection: A Systematic Review and Meta-analysis
Authors: Tariq Raseen , Cho Janice , Kapoor Saloni , Orenstein Robert , Singh Siddharth , Pardi Darrell , Khanna Sahil 
Published: October 2017

Abstract

Background
Efforts towards antibiotic stewardship help reduce risk of Clostridium difficile infection (CDI) but there is a need to delineate antibiotic choices to reduce CDI risk. Tetracyclines may be associated with a low risk for CDI but the evidence is conflicting. We conducted a systematic review and meta-analysis to determine the relationship between tetracyclines use and CDI.

Methods
A systematic search of Medline, Embase, and Web of Science was performed from January 1978 up to December 2016 including studies assessing the association between tetracyclines and CDI; compared with other antibiotics; to assess the risk of CDI after exposure to tetracyclines vs. other antibiotics. Study quality was assessed using the Newcastle-Ottawa scale. Weighted summary estimates were calculated using generalized inverse variance with random-effects model using Review Manager version 5.3 (Cochran Inc).

Results
Six studies; 4 case control and 2 cohort studies reported the association of CDI with tetracyclines or other antibiotics prior to CDI including patients from 1993 to 2012. Meta-analysis of all studies using the random-effects model demonstrated that tetracyclines were associated with decreased risk of CDI compared with other antibiotics (OR, 0.62; 95% CI, 0.47–0.81; P = .0005). There was significant heterogeneity among the studies, with an I2 of 53% (Figure 1). No publication bias was seen.
Subgroup analysis of studies evaluating the risk of CDI with doxycycline only also demonstrated a decreased risk of CDI with doxycycline compared with other antibiotics (OR, 0.55; 95% CI, 0.40–0.75; P = 0.0002). A subgroup analysis based on CDI diagnosis definitions revealed a decreased risk of CDI with tetracyclines (OR, 0.59; 95% CI, 0.44–0.80; P = 0. 0006) in studies that used clinical definitions (presence of diarrhea with a positive stool test), but not among the studies that used ICD-9 codes for CDI diagnosis (OR, 0.95; 95% CI, 0.45–2.01; P = 0.90).

Conclusion
Tetracyclines are associated with a lower risk of developing CDI compared with other antibiotics. It is reasonable to use these over other antibiotics when appropriate (community acquired pneumonia, bronchitis, chlamydia, rickettsial or spirochetal infections) to reduce the risk of CDI.
Forest plot demonstrating decreased odds of CDI with tetracyclines use by a random-effects model

Disclosures
All authors: No reported disclosures.
Clinical and Economic Evaluation of commercialized Fecal Microbiota Transplant (cFMT) for Patients with Recurrent Clostridium difficile Infection (CDI) in a Large Community Hospital
Authors: Hassoun Ali , Edwards Jonathan , Boyett Brian 
Published: October 2017

Abstract

Background
Recurrent CDI is common despite antibiotic therapy. FMT is effective to reduce recurrent infections. We report our experience with Commercialized FMT (cFMT) products by providing ready-to-use capsules, for oral administration, or solution, for administration via colonoscopy.

Methods
The study was approved by IRB for adult patients with at least 3 episode of recurrent CDI despite antibiotic therapy, patients with severe infection were excluded. cFMT was administered in the hospital or at outpatient center. Each patient was evaluated 8 weeks post-transplant to assess for sustained clinical cure and side effects. The economic impact of cFMT was evaluated using historical data from EHR including: CDI rate, CDI readmission rate, rate of CDI-associated death, cost of CDI admissions, and rate of use of each antimicrobial regimen

Results
33 patients enrolled (solution/colonoscopy 20 and capsule 13). Mean age was 74 vs. 67 y, female 56% vs. 64%, recurrent episode 4 vs. 3.1, CDI severity score 1.4 vs. 1.2. 95% (19/20) of patients who received cFMT via colonoscopy experienced sustained clinical cure vs. 85% (11/13) of patients who received capsule. One patient experienced an adverse event from capsule with nausea and vomiting, which resolved without sequelae. 2 of the 3 patients that experienced treatment failure received cFMT from the same donor Due to recurrent episodes. The cost of cFMT was $635 for capsules and $485 for solution which was far less than recurrent CDI associated cost.

Conclusion
cFMT is a viable alternative to traditional FMT and was both clinically and economically beneficial in patients with recurrent CDI in a community hospital. Further studies needed to confirm above findings.

Disclosures
All authors: No reported disclosures.
Cost Effectiveness Analysis of Fecal Transplant Delivery Methods for Recurrent Clostridium difficile Infections in Outpatients
Authors: Walker Jeremey , Gundacker Nathan , Rodriguez Martin , Eaton Ellen 
Published: October 2017

Abstract

Background
Clostridium difficile infection (CDI) accounts for more than $1 billion annually in US health care costs. Recurrent CDI (RCDI, recurrence within 8 weeks of initial treatment) contributes substantially to this cost. The objective of the study was to compare the cost effectiveness of FMT delivered via colonoscopy vs. blind nasogastric tube (NGT) in outpatients. We hypothesized that FMT by NGT would be cost-effective given its low risk and simplicity.

Methods
A decision-analytic simulation model compared the cost effectiveness of FMT by colonoscopy vs. NGT from a third-party payer perspective. Our base case cure rates were derived from a cohort receiving outpatient RCDI treatment at our institution. Cure was defined as resolution of symptoms for ≥ 90 days. Procedural cost and consultation was defined by average reimbursement to a large southeastern medical center in 2016 USD based on current procedural terminology (CPT) codes, and cost of disease states were derived from published literature. Health utilities were defined by quality of life year (QALY) based on published literature. Incremental Cost Effectiveness ratio (ICER) was defined as the cost per additional QALY gained. We assumed a 90 day time horizon. One-way sensitivity analysis was performed on all variables using ranges defined by published literature. We used TreeAge Software (Williamstown, MA).

Results
In the base case, FMT by colonoscopy was dominant (more effective and less costly) than NGT, with cost of $1,568/QALY vs. $1,910/QALY respectively. Cure rates of FMT by colonoscopy vs. NGT (100% vs. 87%) had the largest impact on ICER based on one-way sensitivity analysis. Therefore, a subsequent two-way sensitivity analysis was conducted to compare cure rates of both delivery methods and found that NGT delivery is cost effective as cure rates approach colonoscopy delivery cure rates within 5 percentage points.

Conclusion
Contrary to our hypothesis, our decision model supports FMT by colonoscopy as the preferred delivery method in outpatients with RCDI relative to NGT delivery. Additional costs of colonoscopy delivery are off-set by the improved cure rate leading to lower overall costs. As cure rates from NGT delivery are optimized, NGT may become the preferred method for FMT delivery.

Disclosures
All authors: No reported disclosures.
Ribotypes Matter, Significance of Clostridium difficile Ribotypes in Cancer Patients with Diarrhea
Authors: Guevara Eduardo Yepez , Yalamanchili Harika , Chao Andrew , Garey Kevin , Bhatti Micah , Aitken Samuel L , Okhuysen Pablo C 
Published: October 2017

Abstract

Background
Cancer patients are at increased risk for Clostridium difficile infection (CDI) due to frequent health care contact, chemotherapy, use of antibiotics, and immunosuppression. Distinct ribotypes are associated with CDI adverse outcomes. Ribotypes 14-020 are the predominant ribotypes in many hospitals. We examined the contribution of C. difficile ribotypes to CDI severity, response to therapy and outcomes in this population.

Methods
Demographic and clinical data were collected from 90 cancer patients with a first episode or first recurrence of CDI identified by two-step PCR followed by EIA for A/B toxins. Fluorescent PCR ribotyping (FPCR) was performed on fecal isolates. We identified 27 distinct ribotypes between October 2016 and January 2017. Clinical outcomes were studied in three FPCR subgroups. Group I (GI, n = 27) included F014-020, group II (GII, n = 17) included virulent types 002, 027, 078–126, 244 and group III (GIII, n = 46) included the rest. Treatment failure was defined as no response after at least 3 days of a CDI treatment regimen. CDI severity was determined using Zar’s criteria, presence of bacteremia and ICU stay.

Results
The proportion of patients &gt;50 yrs. old, with health care onset CDI (31%), primary CDI (92.2%), and on active chemotherapy (70%) was similar across the three groups. At presentation, disease severity was similar in all groups; However, patients in GII were more likely to have detectable toxin A/B by EIA compared with GI and GIII (53% vs. 23%, P = 0.015) and higher treatment failure rates (56%) when compared with GI (15% P = 0.007) and GIII (16%, P = 0.004). Bacteremia was more common in GIII (28%) compared with GII (0%) P = 0.041 and GI 7% P = 0.007. Patients in GI experienced fewer complications when compared with those in GIII P = 0.025. No differences in sustained clinical response, recurrence, ICU stay or all cause 90-day mortality were found between the groups.

Conclusion
Cancer patients with CDI due to GII ribotypes are more likely to excrete fecal toxin A/B and fail conventional therapy. In contrast, patients in GI and GIII were more likely to respond to therapy. GI was associated with fewer complications. Of interest, GIII was associated with bacteremia. Evaluation of C. difficile ribotypes is clinically relevant in cancer patients with CDI.

Disclosures
All authors: No reported disclosures.
Successful Response to Microbiota-Based Drug RBX2660 in Patients with Recurrent Clostridium Difficile Infection is Associated with More Pronounced Alterations in Microbiome Profile
Authors: Khanna Sahil , Blount Ken , Jones Courtney , Shannon Bill , Carter Sharina 
Published: October 2017

Abstract

Background
Recurrent Clostridium difficile infections (rCDI) are associated with decreased diversity and altered intestinal microbiome compared with healthy patients. RBX2660, a standardized microbiota-based drug, is designed to restore microbiome diversity and composition in patients’. The effect of RBX2660 on rCDI patient microbiomes was evaluated by comparing pre- and post-treatment samples from PUNCH CD 2—a randomized, double-blind, placebo-controlled study.

Methods
rCDIsubjects were randomized to receive blinded treatments of 2 doses of RBX2660 (Group A), 2 doses of placebo (Group B), or 1 dose each of RBX2660 and placebo (Group C), by enema 7 days apart. Subjects submitted stool samples at baseline, day 7, 30, and 60 after treatment. Stool samples from responders to RBX2660 treatment per protocol defined as the absence of CDI for 8 weeks after treatment were compared with non-responders.
Relative taxonomic abundances at the class level were determined using 16s rRNA sequencing analysis for 94 stool samples from 45 patients in Groups A and C. Relative abundance data were grouped longitudinally using Bray-Curtis dissimilarity index. Analyses were performed based on the Dirichlet-Multinomial distribution to compare group mean relative taxonomic abundances; Simpson and Shannon diversity indices were compared among groups longitudinally.

Results
Baseline patient microbiomes were similar across response groups. RBX2660 treatment shifted the relative microbiome densities with taxa-specific increase in Bacteroidia, Clostridia, and decrease in Gamma-proteobacteria abundance. A larger shift from baseline microbiome was seen in responders to RBX2600 compared with non-responders (Figure 1). Microbiome changes in responders were durable to 60 days. RBX2660 treatment increased Shannon and Simpson diversity at 7 days post-treatment in responders but not in non-responders (P &lt; 0.05).

Conclusion
RBX2660 treatment shifts patient intestinal microbiomes with greater alterations seen in those with a successful clinical outcome.
Funded by Rebiotix Inc., Roseville, MN.

Disclosures
S. Khanna, Rebiotix, Inc.: Scientific Advisor, Consulting fee; K. Blount, Rebiotix, Inc.: Employee, Salary; C. Jones, Rebiotix, Inc.: Employee, Salary; B. Shannon, Rebiotix, Inc.: Research Contractor, Consulting fee; S. Carter, Rebiotix, Inc.: Research Contractor, Consulting fee
Initial Oral Vancomycin vs. Oral Vancomycin After Metronidazole for Severe Clostridium difficile Infection
Authors: Shah Sunish , Ereshefsky Benjamin , Pontiggia Laura , Cawley Michael 
Published: October 2017

Abstract

Background
Treatment of severe Clostridium difficile infection (CDI) with oral vancomycin (oVAN) is known to be superior to treatment with metronidazole. However, previous studies have not evaluated the impact on patients when oVAN therapy is delayed after diagnosis or suspicion of severe CDI.

Methods
This was a single-center, retrospective study of adult patients who were diagnosed with severe CDI as defined by a white blood cell (WBC) count greater than 15,000 cells/mm3. The primary outcome was in-hospital mortality between patients treated initially with oVAN vs. delayed oVAN after metronidazole. Secondary outcomes included clinical cure by day 10, post-infection length of hospitalization, the time to resolution of leukocytosis and renal function at the end of treatment. Leukocytosis was defined as a WBC greater than 12,000 cells/mm3. Patients were excluded if they received oVAN for a previous episode of CDI, were receiving treatment for a concurrent infection, were receiving high-dose steroids, or received metronidazole or oVAN within 5 days preceding CDI diagnosis.

Results
A total of 121 patients were included. Overall, 49% of patients were female and the median age was 67 years old. 101 patients comprised the initial oVAN group, while 20 patients comprised the delayed oVAN group. Baseline demographics did not differ significantly between groups other than the time to initiation of oVAN (0.33 vs. 3.18 days, P &lt; 0.001). There was no significant difference in in-hospital mortality for patients in the initial oVAN treatment group compared with those who had delayed oVAN therapy (5% vs. 15%, P = 0.13). Patients who received oVAN initially experienced a higher rate of clinical cure by day 10 (49.5% vs. 20%, P = 0.02), a shorter median post-infection length of hospitalization (7 days vs. 13 days, P &lt; 0.001), a shorter median time to resolution of leukocytosis (3.9 days vs. 10.4 days, P = 0.01), and were less likely to have an end of treatment serum creatinine greater than 1.5 times their baseline (8.7% vs. 29.4%, P = 0.03).

Conclusion
Patients who receive oVAN as their initial treatment for severe CDI have improved clinical outcomes compared with those initially treated with metronidazole.

Disclosures
All authors: No reported disclosures.
Clostridium difficile Infection in Hematopoietic Stem Cell Transplant Patients: A Single-center Experience
Authors: Majeed Aneela , Larriva Marti , Iftikhar Ahmad , Mushtaq Adeela , Hassan Nida , Hamadani Auon A , Khalid Nageena , Lim Melissa , Zangeneh Tirdad , Anwer Faiz 
Published: October 2017

Abstract

Background
C. difficile infection (CDI) is the most common cause of nosocomial infections in U.S. and leading cause of gastroenteritis associated death. Incidence of CDI in hematopoietic stem cell transplant (HSCT) patients has been reported between 5.7% to 24.7% during first year after HSCT. Literature review reveals many risk factors i.e., allogenic-HSCT, extremes of age, myeloablative conditioning, prior vancomycin resistance (VRE) colonization, pre-transplant C. difficile colonization, severe mucositis, graft vs. host disease (GVHD), duration and type of antibiotics used, immunosuppression, proton pump inhibitor use and NAP1 C. difficile strain.

Methods
To study incidence and different variables for CDI, we performed a retrospective review of medical records of adult patients who underwent HSCT between 2013 and 2016 at our center. REDCap database was used to record key variables related to each patient’s HSCT and CDI, keeping in mind HIPPA guidelines. Categorical data were summed up as percentages and counts and numeric data as means, medians, standard deviations and ranges.

Results
A total of 181 HSCT recipients were included. Incidence of CDI was 10% (18 Patients). Cohort’s most common underlying malignancy was multiple myeloma (35.4%). 70% had autologous HSCT and 30% had allogenic HSCT. Among allogenic transplants, 53% had matched unrelated donor. Peripheral blood was the most common stem cell source (93%). Most common myeloablative conditioning regimen was melphalan (70%). 27% patients were on PPIs. 4% had PEG/NG tube placed and 12% were on TPN. 10% had diabetes mellitus. 5 patients had previous episodes of CDI. 69% developed mucositis. 5% patients developed acute GVHD. 6% had VRE colonization while 66% had no documentation for VRE. Out of positive CDI cases, 17% were NAP1 positive. No episode of ileus or mega colon was documented. Most common treatment regimen were metronidazole 500 mg per orally every 8 hourly (65%) and vancomycin 125 mg per orally four times a day (58.8%).

Conclusion
This single-center study demonstrates that CDI has 10% incidence in patients undergoing HSCT. Risk factors include neutropenia, high dose chemotherapy, mucosal damage and provision of broad spectrum antibiotic prophylaxis. Data on CDI prophylaxis in these patients is emerging and randomized prospective trials are needed.

Disclosures
All authors: No reported disclosures.
Impact of Clostridium difficile Infection on Patients’ Quality of Life: a French Hospital Prospective Study
Authors: Barbut Frederic , Galperine Tatiana , Vanhems Philippe , Le Monnier Alban , Jeanbat Viviane , Duburcq Anne , Alami Sarah , Bensoussan Caroline , Fagnani Francis 
Published: October 2017

Abstract

Background
Few data are available on the impact of episodes of Clostridium difficile infection (CDI) on quality of life. The Cdiff32, a new specific health-related quality of life questionnaire recently validated, allows such a measurement (Garey et al. J Clin Gastroenterol 2016 Sep;50(8):631–7).

Methods
An observational prospective study was performed in 7 French acute-care facilities in 2016. All consecutive patients presenting with a bacteriologically-confirmed CDI during a hospital stay, regardless of reason for hospitalization, were enrolled. Two instruments were presented to patients at 7(±2) days after CDI diagnosis: the Cdiff32 and a generic questionnaire the EQ-5D-3L. The Cdiff32 comprises 32 self-administered questions about the impact of CDI in 3 broad domains (physical, mental and social). The physical domain differentiates general (6 questions) and specific physical complaints (8 questions). The mental domain comprises 14 questions about current and future anxiety. Four questions cover the impact on social relationships. Each item is scored from 0 (worst score) to 100 (best score) and they are aggregated by domain and globally. Clinical variables were collected to characterize the infection severity (ZAR score) and comorbidities. A regression analysis of the Cdiff32 scores with the EQ-5D-3L was performed.

Results
80 patients were enrolled and 3 were excluded because of missing data. The median age was 71 years and 45% were males. The global Cdiff32 score was 50.4 (SD: 17.1) with a large variability among patients (min 18.3, max 90.2). The highest impact of CDI was observed on the general physical complaints (41.6), as well as the level of current anxiety (41.6). The score relating to the social relationships was the highest (63.7). The severity of CDI (as defined by the Zar score) and the global Cdiff32 score were correlated essentially through the physical sub-score (P = 0.0154). Patients with recurrences had a lower mental score compared with patients with an initial episode (P = 0.0582). The regression analysis of global Cdiff32 score and EQ-5D-3L utility score showed a positive relationship (R2=0.317).

Conclusion
The Cdiff32 allowed to estimate the important impact on quality of life of CDI especially on the physical domain.

Disclosures
All authors: No reported disclosures.