Abstract: SA-PO257
One Drug, Different Mechanisms of Side Effects: Linezolid-Induced Thrombocytopenia and Type B Lactic Acidosis
Session Information
- Pharmacology: Kinetics, Genomics, Medication-Related Problems
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Manley, Brock, University of Virginia, Charlottesville, Virginia, United States
- Alghamdi, Ayman M., University of Virginia, Charlottesville, Virginia, United States
- Chopra, Tushar, University of Virginia, Charlottesville, Virginia, United States
Introduction
As the burden of antibiotic-resistant bacteria grows, we must understand the pathophysiology and management of rare side effects of Linezolid.
Case Description
73 yo male with a history of HTN, CKD 3 [baseline serum creatinine(Scr) of 1 mg/dl], and lumbar radiculopathy status post lumbar fusion complicated by infections from Enterobacter cloacae, vancomycin-resistant Enterococci, and methicillin-resistant Staphylococcus aureus (MRSA) treated with- ciprofloxacin 500 mg twice daily for 60 days before admission, 30 days of tedizolid 200 mg daily, and Linezolid 600 mg twice daily for 9 days, leading to this admission.
On admission, the patient had a Scr of 1.6 mg/dl, platelets of 93 K/UL, and lactate of 3.35 mmol/L. Lactate increased to 3.9 mmol/L on hospital day (HD) 1 and returned to normal limits by HD 2 mmol/L. He had a platelet nadir of 43 K/UL on HD 5, along with improvement in Scr to 1.1 mg/dl. Platelet count recovered to 570 K/UL 12 days after admission.
Discussion
Linezolid induced lactic acidosis and thrombocytopenia is diagnosed after excluding other conditions such as hypoxemia, anemia or low cardiac output. Approximately 30% of linezolid is eliminated via the renal route, with an elimination half-life of 5 to 7 hours with the therapeutic trough concentration being 2–8 μg/ml. In patients with impaired renal function, elimination half-life increases from 6.1 to 8.4 hours. Mitochondrial toxicity of linezolid causes severe lactic acidosis usually related to its toxic trough serum levels.
Two mechanisms of LIT have been proposed; decreased platelet production via bone marrow suppression, and immune-mediated platelet destruction. Pharmacokinetic modeling of the two mechanisms found that suppression of platelet formation was the significantly more prominent mechanism of LIT. Immune-mediated platelet destruction typically develops within 7-14 days and recovers rapidly, whilst bone marrow suppression-associated thrombocytopenia develops gradually over multiple weeks and recovers gradually. The latter was observed in this case; a gradual decline and recovery of platelet counts.
One has to consider reducing linezolid dose in patients with renal insufficiency on prolonged treatment to reduce toxicity amongst patients at low risk for treatment failure while being guided by therapeutic drug monitoring.