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

Point/Counterpoint: Are Outstanding Leaders Born or Made?

The question of whether outstanding leaders are born or made has been debated for years. There are numerous examples of historical figures that came naturally to leadership, while others developed their leadership skills through tenacity and experience. To understand leadership, both nature (the genetic component) and nurture (the environmental influences) must be considered. This article represents the work of two Academic Leadership Fellows Program groups who debated each position at the 2016 American Association of Colleges of Pharmacy (AACP) Interim Meeting in Tampa, Fla., in February 2016