Joseph Merlyn, Brady Rebecca, Attridge Russell, Cota Jason, Horlen Cheryl, Lusk Kathleen, Attridge Rebecca L
Irma Lerma Rangel College of Pharmacy, Texas A&M University, Houston, TX, USA.
South Texas Veterans Health Care System, Audie L. Murphy VA Hospital, San Antonio, TX, USA.
Hosp Pharm. 2019 Dec;54(6):378-384. doi: 10.1177/0018578718802583. Epub 2018 Sep 29.
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. This study evaluated how often patients met DILIN criteria when receiving fluconazole daily doses of <6 mg/kg versus ⩾6 mg/kg. : 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. : 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 ( = .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]). : 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.
据估计，氟康唑相关肝损伤在不到10%的患者中发生；然而，基于体重的氟康唑给药对肝损伤的影响尚不清楚。此外，尚无研究系统应用药物性肝损伤网络（DILIN）标准来识别重症监护病房（ICU）环境中可能发生药物性肝损伤的患者。本研究评估了接受每日剂量<6 mg/kg与≥6 mg/kg氟康唑的患者符合DILIN标准的频率。：这项双中心回顾性队列研究在住院的重症氟康唑接受者中进行。我们使用DILIN标准比较了氟康唑开始使用时的肝功能测试（LFTs）与停药后2周内的LFTs峰值。主要目标是评估接受每日剂量<6 mg/kg与≥6 mg/kg氟康唑的患者中符合DILIN标准的人数。次要目标是评估肾功能不全、肝硬化、感染性休克患者或接受负荷剂量患者中符合DILIN标准的患者的发生率。：在纳入的248例患者中，90%有真菌感染记录或接受了疑似侵袭性念珠菌病的经验性治疗。在接受<6 mg/kg氟康唑的患者中，55%（110/199）符合DILIN标准，而在≥6 mg/kg队列中为46.9%（23/49）（P = 0.20）。仅14.5%符合DILIN标准的患者也符合肝细胞损伤的定义。基于体重的氟康唑剂量和肌酐清除率<50 mL/min不是符合DILIN标准的独立危险因素。然而，77.3%的肝硬化患者符合DILIN标准（比值比4.84 [95%置信区间，CI，2.61 - 9.28]），76.3%的感染性休克患者符合DILIN标准（比值比4.56 [95% CI，2.44 - 8.88]）。：基于体重的氟康唑给药并未影响符合DILIN标准的重症接受者的数量。然而，DILIN标准可能高估了重症患者中氟康唑相关肝损伤的发生率。
