Critically Ill Recipients of Weight-Based Fluconazole Meeting Drug-Induced Liver Injury Network Criteria

Background: Fluconazole-associated liver injury is estimated to occur in <10% of patients; however, effect of weight-based fluconazole dosing on liver injury is unknown. Furthermore, no studies have systematically applied the Drug-Induced Liver Injury Network (DILIN) Criteria to identify patients who may have drug-induced liver injury in an intensive care unit (ICU) setting. Objective: This study evaluated how often patients met DILIN criteria when receiving fluconazole daily doses of <6 mg/kg versus ⩾6 mg/kg. Methods: This dual-center, retrospective cohort study was performed in hospitalized critically ill fluconazole recipients. We compared liver function tests (LFTs) upon fluconazole initiation to peak LFTs within 2 weeks after discontinuation using DILIN criteria. The primary objective was to evaluate the number of patients meeting DILIN criteria when receiving fluconazole daily doses of <6 mg/kg versus ⩾6 mg/kg. Secondary objectives were to evaluate incidence of patients meeting DILIN criteria in patients with renal dysfunction, cirrhosis, septic shock, or those receiving a loading dose. Results: Of 248 patients included, 90% had a documented fungal infection or received empiric therapy for suspected invasive candidiasis. In patients receiving <6 mg/kg of fluconazole, 55% (110/199) met DILIN criteria versus 46.9% (23/49) in the ⩾6 mg/kg cohort (P = .20). Only 14.5% of patients meeting DILIN criteria also met the definition for hepatocellular damage. Weight-based fluconazole dose and creatinine clearance <50 mL/min were not independent risk factors for meeting DILIN criteria. However, 77.3% of patients with cirrhosis met DILIN criteria (OR 4.84 [95% confidence interval, CI, 2.61-9.28]) and 76.3% with septic shock met DILIN criteria (OR 4.56 [95% CI, 2.44-8.88]). Conclusion: Weight-based fluconazole dosing did not affect the number of critically ill recipients who met DILIN criteria. However, DILIN criteria may overestimate the incidence of fluconazole-associated liver injury in critically ill patients

Critically-Ill Recipients of Weight-Based Fluconazole Meeting Drug-Induced Liver Injury Network (DILIN) criteria.

Purpose: Fluconazole-associated liver injury is estimated to occur in <10% of patients; however, the effect of weight-based fluconazole dosing on liver injury has not been assessed. This study evaluated how often patients met Drug Induced Liver Injury Network (DILIN) criteria when receiving fluconazole daily doses of <6mg/kg versus ≥6mg/kg. Methods: This multi-center, retrospective cohort study was performed in critically-ill fluconazole recipients hospitalized from January 2009 to December 2012. It included patients who received ≥3 fluconazole doses with ≥1 dose administered in the intensive care unit. Patients were excluded if they were pregnant, presented with acetaminophen toxicity, received fluconazole within 1 week of liver transplantation, or missed >1 fluconazole dose during therapy. We compared liver function tests (LFTs) upon fluconazole initiation to peak LFTs within 2 weeks after fluconazole discontinuation using DILIN criteria. The Fisher’s exact test was used to detect differences in the primary outcome of patients meeting DILIN criteria by weight-based dosing as well as in subgroups of patients with kidney dysfunction, liver disease, septic shock, and those receiving a loading dose. Results: Two-hundred and forty-eight of 767 patients met inclusion criteria; 90% had a documented fungal infection or received empiric therapy for suspected invasive candidiasis. Of the 199 patients receiving <6 mg/kg of fluconazole, 55% met DILIN criteria versus 46.9% of the 49 patients in the ≥6 mg/kg cohort (p=0.20). Only 14.5% of patients meeting DILIN criteria also met the definition for hepatocellular damage. In analysis of subgroups, 77.3% of patients with cirrhosis and 76.3% with septic shock met DILIN criteria (p<0.001 for both compared to those without these conditions). Conclusions: Weight-based fluconazole dosing did not affect the number of critically-ill recipients who met DILIN criteria. However, DILIN criteria may overestimate the incidence of fluconazole-associated liver injury in critically-ill patients

Critically-Ill Recipients of Weight-Based Fluconazole Meeting Drug-Induced Liver Injury Network (DILIN) criteria.

Purpose: Fluconazole-associated liver injury is estimated to occur in <10% of patients; however, the effect of weight-based fluconazole dosing on liver injury has not been assessed. This study evaluated how often patients met Drug Induced Liver Injury Network (DILIN) criteria when receiving fluconazole daily doses of <6mg/kg versus ≥6mg/kg. Methods: This multi-center, retrospective cohort study was performed in critically-ill fluconazole recipients hospitalized from January 2009 to December 2012. It included patients who received ≥3 fluconazole doses with ≥1 dose administered in the intensive care unit. Patients were excluded if they were pregnant, presented with acetaminophen toxicity, received fluconazole within 1 week of liver transplantation, or missed >1 fluconazole dose during therapy. We compared liver function tests (LFTs) upon fluconazole initiation to peak LFTs within 2 weeks after fluconazole discontinuation using DILIN criteria. The Fisher’s exact test was used to detect differences in the primary outcome of patients meeting DILIN criteria by weight-based dosing as well as in subgroups of patients with kidney dysfunction, liver disease, septic shock, and those receiving a loading dose. Results: Two-hundred and forty-eight of 767 patients met inclusion criteria; 90% had a documented fungal infection or received empiric therapy for suspected invasive candidiasis. Of the 199 patients receiving <6 mg/kg of fluconazole, 55% met DILIN criteria versus 46.9% of the 49 patients in the ≥6 mg/kg cohort (p=0.20). Only 14.5% of patients meeting DILIN criteria also met the definition for hepatocellular damage. In analysis of subgroups, 77.3% of patients with cirrhosis and 76.3% with septic shock met DILIN criteria (p<0.001 for both compared to those without these conditions). Conclusions: Weight-based fluconazole dosing did not affect the number of critically-ill recipients who met DILIN criteria. However, DILIN criteria may overestimate the incidence of fluconazole-associated liver injury in critically-ill patients

An Objective Structured Clinical Examination to Assess Pharmacy Resident Performance

Objective: The objective was to utilize an Objective Structured Clinical Examination (OSCE) for assessment of pharmacy residents. Innovation: Post-graduate year 1 (PGY1) and post-graduate year 2 (PGY2) pharmacy residents completing multiple, local residency programs were invited to participate in an OSCE. A total of eight PGY1 residents and one PGY2 resident completed the OSCE. American Society of Health-System Pharmacists (ASHP) residency program goals were aligned for each case, which were originally developed for a fourth-year pharmacy student OSCE. Station design included outpatient and inpatient settings with patient and physician interactions. Median communication and clinical skills scores were evaluated. Critical Analysis: The OSCE allows for assessment of all residents on common scenarios. Pharmacy residents met competency requirements and demonstrated excellent communication skills. The OSCE was able to evaluate both physician-pharmacist communication and patient-pharmacist communication. Baseline performance related to the ASHP goals and objectives was not completed; however, the OSCE could highlight resident strengths and weaknesses in communication and clinical skills. The OSCE could simulate independent practice, may reduce bias, and could provide an evaluation of the resident by a patient. However, the OSCE incurs higher resource utilization, specifically monetary and time, than other assessment methods. Next Steps: The pilot study results provide a beginning for further study of OSCEs for pharmacy residents. Further study should include surveying the residency directors about use of the OSCE, a comparison of performance between the OSCE and preceptor evaluations of residents on ASHP goals and objectives, and an evaluation of OSCE implementation at different time points within the residency. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties &nbsp; Type:&nbsp;Not

Evaluation of prophylactic antibiotic regimens on recurrence and mortality in spontaneous bacterial peritonitis

Introduction and objectives: Limited data describe current SBP epidemiology and specific secondary SBP prophylactic regimens, leading to variable prescribing practices. This work aims to compare 90-day and one-year SBP recurrence and mortality based on secondary SBP antibiotic prophylaxis regimens. Materials and methods: We performed a retrospective cohort of patients >18 years with an SBP diagnosis from 2010 to 2015 at two academic institutions. Eligible patients had ascitic PMN counts ≥250 cells/mm3 or a positive ascitic culture. Patients were compared based on secondary SBP prophylaxis regimens (i.e., daily, intermittent, or no prophylaxis). Results: Of 791 patients with ascitic fluid samples, 86 patients were included. Antibiotic prophylaxis included daily (n = 34), intermittent (n = 36), or no prophylaxis (n = 16). Nearly half of SBP episodes had a positive ascitic fluid culture; 50% were gram-negative pathogens, and 50% were gram-positive pathogens. Daily and intermittent regimens had similar rates of recurrence at 90-days (19.4% vs. 14.7%, p = 0.60) and one-year (33.3% vs. 26.5%, p = 0.53). Similarly, mortality did not differ among daily and intermittent regimens at 90-days (32.4% vs. 30.6%, p = 0.87) or one-year (67.6% vs. 63.9%, p = 0.74). When comparing any prophylaxis vs. no prophylaxis, there were no differences in 90-day or one-year recurrence or mortality. Conclusions: In patients with a history of SBP, our data indicate similar outcomes with daily, intermittent, or no secondary antibiotic prophylaxis. With available data, including ours, demonstrating a changing epidemiology for SBP pathogens, further data is required to determine if traditional approaches to secondary SBP prophylaxis remain appropriate

Pharmacologic strategies for management of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is defined as a mean pulmonary artery pressure ≥ 25 mmHg at rest with a pulmonary wedge pressure 15 mmHg and a pulmonary vascular resistance \u3e 3 Wood units measured by right cardiac catheterization. Increased awareness of the progressive nature of the disease has led to earlier evaluation, identification, and therapy. Management of PAH includes non-pharmacologic therapy as well as background and targeted medical therapy. Background therapy may include diuretics, digoxin, oxygen, and anticoagulation for specific patients. Five classes of targeted medical therapy are currently available to manage PAH, including prostacyclin analogs, endothelin receptor antagonists, phosphodiesterase inhibitors, a soluble guanylate cyclase stimulator, and a prostacyclin IP receptor agonist. Recent evidence shows that initial combination therapy with some of these agents reduces the time to clinical failure and the incidence of PAH-related hospitalizations