Citations

Background and Aims: Clostridium difficile infection (CDI) has been associated with an increased mortality risk among patients with inflammatory bowel disease (IBD) in multiple observational studies. We performed a systematic review and meta-analysis to help clearly define the magnitude of risk in IBD patients with and without CDI, and to assess the risk in individual IBD subtypes. Methods: A systematic search of multiple electronic databases was conducted for observational studies reporting the risk of mortality in IBD, stratified by the presence of CDI. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. Results: Ten observational studies were identified (8 from North America and 2 from Europe) and included 40,700 IBD patients with CDI and 1,320,764 IBD controls without CDI. Overall, IBD patients with CDI had a higher risk of mortality compared with IBD patients without CDI [odds ratios (OR), 4.39; 95% confidence interval (CI), 3.56-5.42; I 2=93%]. The results were stable in high-quality studies and in hospitalized patients. When patients were stratified by IBD type, CDI was associated with increased mortality in patients with ulcerative colitis (7 studies) (OR, 4.39; 95% CI, 3.44-5.61; I 2), but not in patients with Crohn’s disease (4 studies) (OR, 2.21; 95% CI, 0.84-5.77; I 2). Individual studies were limited by an inability to control for IBD disease activity and therapeutic interventions. Conclusions: On the basis of 10 observational studies with at least moderate quality, CDI seems to increase mortality risk in IBD, particularly in ulcerative colitis. These findings are a cause for concern and suggest that CDI should be managed aggressively in patients with IBD.

AbstractBackground and AimAcute kidney injury (AKI) is used as a marker of severity in Clostridium difficile infection (CDI) patients. We estimated the true effect of AKI in inpatient mortality of CDI patients, as there are no large‐scale, population‐based, propensity‐matched studies evaluating AKI's effect in this patient cohort.MethodsA retrospective observational study utilizing the National Inpatient Sample from years 2003 to 2012, including all adults with CDI, excluding cases missing data on age, inpatient mortality or gender. Trends and CDI‐related complications as mortality predictors were assessed using survey‐weighted multivariable regression. We estimated AKI's independent effect by propensity‐matching, post‐stratifying by chronic kidney disease status, allowing for multiple comorbidity adjustment.ResultsA total of 2 859 599 patients with CDI were included, of which 896 122 (31.3%) had principal diagnosis of CDI. AKI prevalence was 22%. Mortality rate was 8.4%, while among AKI patients was higher (18.2%). In multivariable regression, AKI was associated with higher mortality (odds ratio [OR] = 3.16, 95% confidence interval [CI]: 3.02–3.30; P < 0.001), while after propensity matching, AKI increased mortality by 86% (OR = 1.86, 95% CI: 1.79–1.94; P < 0.001). CDI incidence increased by 1.8, together with the rate of AKI (12.6% in 2003 to 28.8% in 2012, P‐trend < 0.001). Despite increasing hospitalizations, mortality over the study period decreased to 7.2% (2012) from 9.0% (2003); P‐trend < 0.001.ConclusionHospital admissions of patients with CDI and concomitant AKI are increasing, but their inpatient mortality has improved over the study period. AKI is a significant contributor to mortality, independently of other comorbidities, complications, and hospital characteristics, emphasizing the need for early diagnosis and aggressive management in such patients.

69 Background: Due to improved survival, an increasing number of patients with advanced cancer are eligible for aggressive ICU care, including intubation. The American Society of Clinical Oncology recommends early integration of palliative care in patients with advanced cancer. We analyzed 10-year trends in the utilization of palliative care, and predictors of palliative care use in patients with metastatic cancer undergoing intubation using the National Hospital Discharge Survey database from 2001-2010. Methods: Diagnosis and procedure codes were utilized to identify adult patients with metastatic cancer who underwent intubation, and received palliative care. Demographics, diagnoses, length of stay (LOS), and discharge information were extracted. T-tests and χ^2 tests were used to compare medians and proportions respectively in patients that did or did not receive palliative care. Multivariate regression models with weighted analysis were conducted to study predictors of palliative care use. Results: Over the 10-year study period, 200,350 patients with metastatic cancer and intubation were identified, mean age 65.3 years, 46.2% male. Of these, 6690 (3.3%) received palliative care. There was a significant increase in the use of palliative care from 2001 (0%) to 2010 (17.4%), p for trend < 0.001. In multivariate analysis, patients who received palliative care were more likely to have age > 65 years, be white vs non-white, be hospitalized in 2009-2010 vs 2000-2001, and be admitted to hospitals in the Western part of the US. The overall inpatient mortality rate was 57.3%, discharge to a care facility (DTCF) rate was 15.2%, and mean LOS was 11.1 days. The LOS and DTCF rates were similar in patients with and without palliative care. Patients with palliative care had higher rates of inpatient mortality (adjusted OR 9.6, 95% CI 2.2- 42.0). Conclusions: There was a dramatic increase in the use of palliative care in intubated patients with metastatic cancer. Studies to address the racial and geographic discrepancies in palliative care use are warranted. The higher mortality in palliative care group suggests it is being used for the sickest patients. Early (vs end of life) palliative care may be more beneficial.

There has been an increasing interest in the association between human disease and altered gut microbiota, and therapeutics to modulate microbiota to treat disease. Healthy human gastrointestinal microbiota is highly diverse and rich, and harbors between 500 and 2,000 species. Diseases associated with dysbiotic microbiota include antibiotic‐associated diarrhea, Clostridium difficile infection, multidrug‐resistant organisms, inflammatory bowel disease, obesity, metabolic syndrome, diabetes mellitus, neuropsychiatric diseases, and systemic autoimmune diseases. Microbiota replacement therapies have shown immense promise in treatment of recurrent C. difficile infection and are being studied for other indications. Microbiota replacement therapies for indications other than C. difficile infection should be performed only in research settings. There is an immense need for standardized microbiota replacement therapies for C. difficile infection. Studies are needed to elucidate long‐term safety and adverse events from these therapies.

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

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.