VORICONAZOLE-INDUCED HEPATOTOXICITY USED FOR SCEDOSPORIUM AIRWAY COLONIZATION SUPPRESSION THERAPY IN A PATIENT WITH A HISTORY OF A DOUBLE LUNG TRANSPLANT

TOPIC: Transplantation TYPE: Medical Student/Resident Case Reports INTRODUCTION: Voriconazole-induced hepatoxicity is a well known dose-dependent adverse drug reaction. Its non-linear kinetics provides unique challenge to clinicians for therapeutic monitoring, in addition eliciting diagnosis. CASE PRESENTATION: A 30-year-old female with PMHx of cystic fibrosis s/p bilateral lung transplant 9/2019 Scedosporium plaques diagnosed via BAL 10/2019, IDDM2, history loculated pericardial effusion decortication, recurrent polymicrobial airway colonization, and severe malnutrition requiring PEG tube placement 11/2019 who presented the ED complaints nausea 4 days. She was found have mixed high-anion & normal anion gap metabolic acidosis compensatory incomplete respiratory alkalosis (serum bicarbonate 6 serum 23), transaminitis synthetic function (AST > 931, ALT 394, GGT 1233), RTA Type I positive urine pH < 5.5. CT A/P negative. Physical exam revealed no scleral icterus or jaundice, abdomen soft, flat, non-tender hypoactive bowel sounds.The patient then given IVF w/ NS IV antibiotics per sepsis protocol due SIRS criteria tachycardia leukocytosis. Sodium also initiated her acid-base disorder. The team contacted recommended obtaining Voriconazole levels, which were be 16 mcg/mL (ref range: 1.0 - 5.5 mcg/mL). temporarily held abnormal LFTs, Mycophenolate, Valganciclovir, Prednisone continued. Her subsequently resolved discontinuation Voriconazole, she discharged home days later close follow up team. DISCUSSION: patient's symptoms can explained by hepatotoxic effects suppressive anti-fungal therapy. on 600 mg oral twice daily, approximately dose specific indication (1). systemic therapy used prophylaxis pre-transplanst fungal colonization (2). Appropriate doses depend whether patients are calcineurin inhibitors, typically CYP450 taking into account that increased hepatic metabolism liver clearance (3). Our first 1/2013. However, steadily over time lack response, may attributed overall poor nutritional status as Voriconzaole has decreased bioavailability chronically malnourished CONCLUSIONS: It imperative consider toxic levels medications undergone transplant, including but not limited agents, other immunosuppressants. REFERENCE #1: Troke P, Aguirrebengoa K, Arteaga C, Ellis D, Heath CH, Lutsar I, Rovira M, Nguyen Q, Slavin Chen SC; Global Study Group. Treatment scedosporiosis voriconazole: clinical experience 107 patients. Antimicrob Agents Chemother. 2008 May;52(5):1743-50. doi: 10.1128/AAC.01388-07. Epub Jan 22. PMID: 18212110; PMCID: PMC2346616. #2: Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young Bennett JE. Practice Guidelines Diagnosis Management Aspergillosis: 2016 Update Infectious Diseases Society America. Clin Infect Dis. Aug 15;63(4):e1-e60. 10.1093/cid/ciw326. Jun 29. 27365388; PMC4967602. #3: M. Berge, G. V. Boussaud, H. Phamm et al., "Voriconazole pharmacokinetic variability patients," Transplant Disease, vol. 11, no. 3, pp. 211–219, 2009. DISCLOSURES: No relevant relationships Maie Abdullah, source=Web Response Kareem Ebeid, Zachary Jones,