Probiotics in hospitalized adult patients: a systematic review of economic evaluations.

PURPOSE: Probiotics may prevent healthcare-associated infections, such as ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and other adverse outcomes. Despite their potential benefits, there are no summative data examining the cost-effectiveness of probiotics in hospitalized patients. This systematic review summarized studies evaluating the economic impact of using probiotics in hospitalized adult patients. METHODS: We searched MEDLINE, EMBASE, CENTRAL, ACP Journal Club, and other EBM reviews (inception to January 31, 2019) for health economics evaluations examining the use of probiotics in hospitalized adults. Independently and in duplicate, we extracted data study characteristics, risk of bias, effectiveness and total costs (medications, diagnostics/procedures, devices, personnel, hospital) associated with healthcare-associated infections (ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea and antibiotic-associated diarrhea). We used Grading of Recommendations Assessment, Development and Evaluation methods to assess certainty in the overall cost-effectiveness evidence. RESULTS: Of 721 citations identified, we included seven studies. For the clinical outcomes of interest, there was one randomized-controlled trial (RCT)-based health economic evaluation, and six model-based health economic evaluations. Probiotics showed favourable cost-effectiveness in six of seven (86%) economic evaluations. Three of the seven studies were manufacturer-supported, all which suggested cost-effectiveness. Certainty of cost-effectiveness evidence was very low because of risk of bias, imprecision, and inconsistency. CONCLUSION: Probiotics may be an economically attractive intervention for preventing ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and antibiotic-associated diarrhea in hospitalized adult patients. Nevertheless, certainty about their cost-effectiveness evidence is very low. Future RCTs examining probiotics should incorporate cost data to inform bedside practice, clinical guidelines, and healthcare policy. TRIAL REGISTRATION: PROSPERO CRD42019129929; Registered 25 April, 2019.

Fidaxomicin versus Vancomycin as a First-Line Treatment for Clostridium difficile-Associated Diarrhea in Specific Patient Populations: A Pharmacoeconomic Evaluation.

OBJECTIVES: The reduction in recurrent Clostridium difficile-associated diarrhea (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to lower overall CDAD costs. However, studies assessing the cost-effectiveness of fidaxomicin as first-line therapy from the U.S. hospital perspective are lacking. This study evaluated the costs associated with utilizing fidaxomicin or vancomycin as a first-line therapy for CDAD in specific patient populations from a U.S. hospital perspective. METHODS: A decision-analytic model was developed to estimate total costs (hospitalization and drug costs) associated with using fidaxomicin or vancomycin as first-line therapy for a first episode and up to two recurrences of CDAD in five patient populations: general population, elderly, patients receiving concomitant antibiotics, and patients with renal impairment or cancer. RESULTS: The total cost of CDAD treatment using fidaxomicin first line in the general population was $14,442 per patient versus $14,179 per patient with vancomycin first line. In subgroup analyses, fidaxomicin use resulted in total hospital cost savings of $616 per patient in patients with cancer and $312 in patients with concomitant antibiotic use; vancomycin use was associated with total hospital cost savings of $243 per patient in the elderly and $371 in patients with renal impairment. CONCLUSIONS: Fidaxomicin as first-line CDAD therapy is associated with similar total costs as compounded vancomycin oral solution in the general population. In elderly and renally impaired patients, slight increases in hospital cost were observed with fidaxomicin therapy, and in patients with cancer or concomitant antibiotic use, hospital cost savings were observed.

Impact of end stage kidney disease on costs and outcomes of Clostridium difficile infection.

OBJECTIVES: To assess the impact of end stage kidney disease (ESKD) on the outcomes of Clostridium difficile infection (CDI), including complications of infection, length of hospital stay, overall mortality, and healthcare burden. METHODS: The National Inpatient Sample (NIS) database created by the Agency of Healthcare Research and Quality (AHRQ) was used, covering the years 2009 through 2013. Manufacturer-provided sampling weights were used to produce national estimates. RESULTS: All-cause unadjusted in-hospital mortality was significantly higher for patients with CDI and ESKD than for patients without ESKD (11.6% vs. 7.7%, p<0.001). The in-hospital mortality remained higher even after adjusting for age, sex, race, and Charlson index group using multivariate logistic regression (odds ratio 1.47, confidence interval 1.41-1.53). The median length of stay was found to be longer by 2days in the ESKD group (9 vs. 7 days, p<0.001). The average cost of hospitalization for patients with CDI and ESKD was also significantly higher compared to the non-ESKD group (USD $35 588 vs. $23 505, in terms of the 2013 value of the USD, p<0.001). CONCLUSIONS: The presence of end stage kidney disease in hospitalized patients with Clostridium difficile infection is associated with higher mortality, a longer length of stay, and a higher cost of hospitalization.

Disproportionate rise in Clostridium difficile-associated hospitalizations among US youth with inflammatory bowel disease, 1997-2011.

OBJECTIVES: Our aim was to characterize the temporal changes in burden that Clostridium difficile infection (CDI) added to the hospital care of children and young adults with inflammatory bowel disease (IBD) in the United States. METHODS: Retrospective analysis of annual, nationally representative samples of children and young adults with IBD. RESULTS: There was a 5-fold increase in IBD hospitalizations with CDI from 1997 to 2011 (P for trend <0.01). During the same period, IBD hospitalizations without CDI increased 2-fold (P for trend <0.01). Mean length of stay for IBD hospitalizations with CDI was consistently longer than that for hospitalizations without CDI and did not significantly change over time (P for trend = 0.47). CDI-related total hospital days in the United States rose from 1702 to 10,194 days per million individuals per year from 1997 to 2011 (P for trend <0.01). Children and young adults hospitalized with CDI had a significantly lower odds of colectomy (0.31) compared with those without CDI. Total charges for CDI-related hospitalizations among children and young adults in the United States rose from $8.7 million in 1997 to $68.2 million in 2011. CONCLUSIONS: A widening gap in burden has opened between IBD hospitalizations with and without CDI during the last decade and a half. CDI-related hospitalizations are associated with disproportionately longer lengths of stay, more hospital days, and more charges than hospitalizations without CDI over time. Further work within health systems, hospitals, and practices can help us better understand this enlarging gap to improve clinical care for this vulnerable population.

Infection-related hospitalizations are associated with increased mortality in patients with inflammatory bowel diseases.

INTRODUCTION: Serious infections are an important side effect of immunosuppressive therapy used to treat Crohn's disease (CD) and ulcerative colitis (UC). There have been no nationally representative studies examining the spectrum of infection related hospitalizations in patients with IBD. METHODS: Our study consisted of all adult CD and UC related hospitalizations from the Nationwide Inpatient Sample 2007, a national hospitalization database in the United States. We then identified all infection-related hospitalizations through codes for either the specific infections or disease processes (sepsis, pneumonia, etc.). Predictors of infections as well as the excess morbidity associated with infections were determined using multivariate regression models. RESULTS: There were an estimated 67,221 hospitalizations related to infections in IBD patients, comprising 27.5% of all IBD hospitalizations. On multivariate analysis, infections were independently associated with age, co-morbidity, malnutrition, TPN, and bowel surgery. Infection-related hospitalizations had a four-fold greater mortality (OR 4.4, 95% CI 3.7-5.2). However, this varied by type of infection with the strongest effect seen for sepsis (OR 15.3, 95% CI 12.4-18.6), pneumonia (OR 3.6, 95% CI 2.9-4.5) and C. difficile (OR 3.2, 95% CI 2.6-4.0), and weaker effects for urinary infections (OR 1.4, 95%CI 1.1-1.7). Infections were also associated with an estimated 2.3 days excess hospital stay (95% CI 2.2-2.5) and $12,482 in hospitalization charges. CONCLUSION: Infections account for significant morbidity and mortality in patients with IBD and disproportionately impact older IBD patients with greater co-morbidity. Pneumonia, sepsis and C difficile infection are associated with the greatest excess mortality risk.