Tariq, Raseen

Abstract Introduction: C. difficile infection (CDI) is a common nosocomial infection. Immune suppression is thought to be a major risk factor for CDI. Hematopoietic stem cell transplant (HSCT) recipients represent a major subgroup of immunologically vulnerable patients. It is unclear if these patients have novel risk factors for CDI development. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of CDI in HSCT recipients. Methods: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to June 2018. All studies that assessed risk factors associated with CDI development in HSCT recipients were eligible for inclusion. Data on clinical characteristics and risk factors associated with CDI development were collected. Study quality was assessed using the Newcastle-Ottawa scale. Meta-analyses were performed using random effects models and pooled odds ratios with 95% confidence interval (CI) for risk factors reported in ≥ 2 studies were calculated. Results: Overall, 17 studies, including 6328 HSCT patients were included. Of those 874 patients developed CDI. The rate of CDI development in these patients was 13.81% with a follow up ranging from 1- 36 months. A total of 34 different risk factors were studied, of which 20 were identified in ≥ 2 studies. Our analysis showed that cephalosporin use (Odds ratio [OR] 2.21, 95% confidence interval [CI] 1.26-3.87), cord blood transplant (OR 1.36, 95% CI 1.01-1.83), graft versus host disease (GVHD) (OR 1.63, 95% CI 1.07-2.48) & prior hospitalization within 90 days of HSCT (OR 1.85, 95% CI 1.21-2.83) were associated with statistically significant increased risk of CDI in HSCT patients (Figure 1). On the other hand, many characteristics of HSCT patients including age, diabetes, lung disease, fluoroquinolones, proton pump inhibitors, rituximab, mucositis, myeloablative therapy, melphalan use before BMT, total body irradiation, growth factor use during admission, neutropenia, autologous vs allogenic transplant and use of matched related donor were not associated with increased risk of CDI. Conclusion: HSCT recipients are at an increased risk of CDI compared to general population. In addition to the common risk factors like cephalosporin use and prior hospitalization, these patients have novel characteristics including presence of GVHD and cord blood transplant that puts them at a higher risk of CDI. HSCT patients with these risk factors may warrant a closer surveillance for early detection and treatment of CDI. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Graft versus Host disease (GVHD) is a major cause of mortality and morbidity in allogenic hematopoietic stem cell transplant recipients (HSCT). Gut microbiome dysbiosis secondary to conditioning regimens (which include antibiotics) in HSCT, appears to play a significant role in gut GVHD development through its interaction with the immune system. Fecal Microbiota Transplantation (FMT) has been explored for the treatment of gut GVHD owing to its ability to restore the gut microbiome. We performed a systemic review and meta-analysis to review the efficacy and safety of FMT for gut GVHD. METHODS: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 through May 2019. Articles included for meta-analysis were observational studies which included patients with steroid-dependent or resistant gut GVHD after HSCT who underwent one or more FMTs. The main outcomes were pooled proportions of patients achieving response defined as a decrease in gastrointestinal symptoms including stool volume and frequency or reduction of steroid or immunosuppressant dose. Partial response was defined as a decrease of gastrointestinal symptoms followed by recurrence of symptoms. RESULTS: Five studies (4 prospective single arm pilot studies and 1 retrospective case series) including 37 patients were included with follow up ranging from 1–13 months. Three studies used naso-duodenal route, one used oral capsules and one used colonoscopy for FMT. Median number of FMTs per study was 2 (range, 1–6). Unrelated donors were used in 4 studies. A total of 23/37 patients achieved complete response with a pooled proportion of 61.0% (95% confidence interval [CI] 46–76.0), with no heterogeneity (I 2 = 0%). Partial response was seen in 3 patients. Hence, the overall response rate was 74.0% (95% CI 49–93, I 2 53%). FMT was generally well tolerated. No treatment-related mortality was reported by any study. Serious adverse events were reported in 3 patients (hypoxia in one patient and bacteremia in two patients) but were not directly attributed to FMT. CONCLUSION: FMT is a promising modality for management of gut GVHD and appears to be safe as a salvage therapy based on the current limited data. Ongoing placebo-controlled prospective clinical trials will help to further establish its safety and efficacy.

e18244 Background: Clostridioides difficile infection (CDI) has higher incidence in cancer patients. To characterize the extent of CDI burden among hematologic cancer patients, we used the National Hospital Discharge Survey (NHDS) to report the incidence and outcomes of CDI. Methods: NHDS data from 2001-2010 were analyzed using diagnosis codes to identify patients with hematologic cancers and CDI. Demographics and discharge information were compared amongst hematologic cancer patients with and without CDI. Logistic regression models were runto estimate the impact of CDI on hematologic cancer patient outcomes, using STATA 12.0. Results: During the years 2001-2010, about 3.7 million patients (weighted data) were discharged with hematologic cancer. Among them, the incidence of CDI was 2.3%. Hematologic cancer patients with CDI were younger (mean age 66 vs 68 years), more likely to be men (66% vs 64.5%), to be of white race (68.1% vs 67.7%) and to have emergent admissions (73% vs 69%), all p values < 0.001. CDI incidence in these patients showed a steeper increase than non-cancer patients, with highest incidence in 2008-2009. Hematologic cancer patients with CDI had a longer mean Length of stay (16.9 vs 7.1 days; adjusted odds ratio (aOR) 9.5, 95% CI 9.4-9.6), all cause hospital mortality (11.3% vs 6.3%; aOR 1.92, 95% CI 1.88-1.97) and discharge to a care facility (28.4% vs 18.8%; aOR 2.06, 95% CI 2.02-2.10) compared to non-CDI cancer patients. Conclusions: CDI incidence is higher in patients with hematologic malignancy. They also have worse outcomes including overall mortality, longer hospitalizations and discharge to healthcare facility. These patients warrant closer screening and prompt treatment of CDI as they are at greater risk of unfavorable outcomes. [Table: see text]

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.

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.

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.