BACKGROUND Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy,but patients currently or recently treated with antibiotics were frequently excluded from studie...BACKGROUND Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy,but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy.Due to overlapping spectrums of activity,combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary.A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease.It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs.AIM To determine the clinical,safety,and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients.METHODS This was a single-center,quasi-experimental,pre-post study based on a pilot pharmacist-driven protocol.Patients in the protocol group were prospectively identified via the medical intensive care unit(ICU)(MICU)protocol to have rifaximin withheld during broad-spectrum antibiotic treatment.These were compared to a historical cohort who received combination therapy with broadspectrum antibiotics and rifaximin.All data were collected retrospectively.The primary outcome was days alive and free of delirium and coma(DAFD)to 14 d.Safety outcomes included MICU length of stay,48-h change in vasopressor dose,and ICU mortality.Secondary outcomes characterized rifaximin cost savings and protocol adherence.Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors.RESULTS Each group included 32 patients.The median number of delirium-and coma-free days was similar in the control and protocol groups[3 interquartile range(IQR 0,8)vs 2(IQR 0,9.5),P=0.93].In multivariable analysis,group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d.The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy[6 d control(IQR 3,9.5)vs 1 d protocol(IQR 0,1);P<0.001].Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements.Overall adherence to the protocol was 91.4%.The median estimated total cost of rifaximin therapy per patient was reduced from$758.40(IQR$379.20,$1200.80)to$126.40(IQR$0,$126.40),P<0.01.CONCLUSION The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.展开更多
BACKGROUND Patients with liver disease are concomitantly at increased risk of venous thromboembolism(VTE) and bleeding events due to changes in the balance of pro-and anti-hemostatic substances. As such, recommendatio...BACKGROUND Patients with liver disease are concomitantly at increased risk of venous thromboembolism(VTE) and bleeding events due to changes in the balance of pro-and anti-hemostatic substances. As such, recommendations for the use of pharmacological VTE prophylaxis are lacking. Recent studies have found no difference in rates of VTE in those receiving and not receiving pharmacological VTE prophylaxis, though most studies have been small. Thus, our study sought to establish if pharmacological VTE prophylaxis is effective and safe in patients with liver disease.AIM To determine if there is net clinical benefit to providing pharmacological VTE prophylaxis to cirrhotic patients.METHODS In this retrospective study, 1806 patients were propensity matched to assess if pharmacological VTE prophylaxis is effective and safe in patients with cirrhosis.Patients were divided and evaluated based on receipt of pharmacological VTE prophylaxis.RESULTS The composite primary outcome of VTE or major bleeding was more common in the no prophylaxis group than the prophylaxis group(8.7% vs 5.1%, P = 0.002),though this outcome was driven by higher rates of major bleeding(6.9% vs 2.9%,P < 0.001) rather than VTE(1.9% vs 2.2%, P = 0.62). There was no difference inlength of stay or in-hospital mortality between groups. Pharmacological VTE prophylaxis was independently associated with lower rates of major bleeding(OR = 0.42, 95%CI: 0.25-0.68, P = 0.0005), but was not protective against VTE on multivariable analysis.CONCLUSION Pharmacological VTE prophylaxis was not associated with a significant reduction in the rate of VTE in patients with liver disease, though no increase in major bleeding events was observed.展开更多
BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on...BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver failure.AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial infections.METHODS From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial infections.We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts.Data was extracted through chart review.RESULTS All fungal infections were due to Candida species,and were most frequently blood isolates.Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,P<0.001).The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,P=0.02).Patients in the fungal cohort had increased use of vasopressors(96%vs 70%,P=0.04),mechanical ventilation(96%vs 65%,P<0.001),and dialysis due to acute kidney injury(78%vs 52%,P=0.014).On MILU admission,the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation(108 vs 91,P=0.003),Acute Physiology Score(86 vs 65,P=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,P=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,P=0.2).Patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical significance.CONCLUSION Mortality was worse among patients with fungal infections,likely attributable to severe ACLF development.Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.展开更多
文摘BACKGROUND Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy,but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy.Due to overlapping spectrums of activity,combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary.A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease.It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs.AIM To determine the clinical,safety,and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients.METHODS This was a single-center,quasi-experimental,pre-post study based on a pilot pharmacist-driven protocol.Patients in the protocol group were prospectively identified via the medical intensive care unit(ICU)(MICU)protocol to have rifaximin withheld during broad-spectrum antibiotic treatment.These were compared to a historical cohort who received combination therapy with broadspectrum antibiotics and rifaximin.All data were collected retrospectively.The primary outcome was days alive and free of delirium and coma(DAFD)to 14 d.Safety outcomes included MICU length of stay,48-h change in vasopressor dose,and ICU mortality.Secondary outcomes characterized rifaximin cost savings and protocol adherence.Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors.RESULTS Each group included 32 patients.The median number of delirium-and coma-free days was similar in the control and protocol groups[3 interquartile range(IQR 0,8)vs 2(IQR 0,9.5),P=0.93].In multivariable analysis,group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d.The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy[6 d control(IQR 3,9.5)vs 1 d protocol(IQR 0,1);P<0.001].Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements.Overall adherence to the protocol was 91.4%.The median estimated total cost of rifaximin therapy per patient was reduced from$758.40(IQR$379.20,$1200.80)to$126.40(IQR$0,$126.40),P<0.01.CONCLUSION The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.
文摘BACKGROUND Patients with liver disease are concomitantly at increased risk of venous thromboembolism(VTE) and bleeding events due to changes in the balance of pro-and anti-hemostatic substances. As such, recommendations for the use of pharmacological VTE prophylaxis are lacking. Recent studies have found no difference in rates of VTE in those receiving and not receiving pharmacological VTE prophylaxis, though most studies have been small. Thus, our study sought to establish if pharmacological VTE prophylaxis is effective and safe in patients with liver disease.AIM To determine if there is net clinical benefit to providing pharmacological VTE prophylaxis to cirrhotic patients.METHODS In this retrospective study, 1806 patients were propensity matched to assess if pharmacological VTE prophylaxis is effective and safe in patients with cirrhosis.Patients were divided and evaluated based on receipt of pharmacological VTE prophylaxis.RESULTS The composite primary outcome of VTE or major bleeding was more common in the no prophylaxis group than the prophylaxis group(8.7% vs 5.1%, P = 0.002),though this outcome was driven by higher rates of major bleeding(6.9% vs 2.9%,P < 0.001) rather than VTE(1.9% vs 2.2%, P = 0.62). There was no difference inlength of stay or in-hospital mortality between groups. Pharmacological VTE prophylaxis was independently associated with lower rates of major bleeding(OR = 0.42, 95%CI: 0.25-0.68, P = 0.0005), but was not protective against VTE on multivariable analysis.CONCLUSION Pharmacological VTE prophylaxis was not associated with a significant reduction in the rate of VTE in patients with liver disease, though no increase in major bleeding events was observed.
文摘BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver failure.AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial infections.METHODS From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial infections.We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts.Data was extracted through chart review.RESULTS All fungal infections were due to Candida species,and were most frequently blood isolates.Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,P<0.001).The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,P=0.02).Patients in the fungal cohort had increased use of vasopressors(96%vs 70%,P=0.04),mechanical ventilation(96%vs 65%,P<0.001),and dialysis due to acute kidney injury(78%vs 52%,P=0.014).On MILU admission,the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation(108 vs 91,P=0.003),Acute Physiology Score(86 vs 65,P=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,P=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,P=0.2).Patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical significance.CONCLUSION Mortality was worse among patients with fungal infections,likely attributable to severe ACLF development.Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.