LVAD- Antibiotic and Warfarin Alert

Abstract

<h3>Introduction</h3> Three of the main causes of early and late morbidity and mortality in Ventricular Assist Device (VAD) recipients include infections, bleeding and thrombosis. Infections directly or indirectly associated to VAD are common and often requiring prolonged courses of intravenous antibiotics. Anti-vitamin K anticoagulants are known to interact with many drugs including antimicrobial agents. This case report highlights the risks of an important drug-drug interaction that has the potential to result in serious consequences. <h3>Case Report</h3> A 45-year-old male with LVAD (HeartWare) presented with an episode of significant hypotension (MAP 40mmHg) and was admitted to the Intensive Care Unit and initiated on vancomycin and Tazocin for empiric coverage of a suspected VAD-related infection. He was subsequently diagnosed with a methicilin sensitive Staphylococcus aureus (MSSA) bacteraemia. Vancomycin was changed to I-V flucloxacillin 8 g daily. No clear source of sepsis was demonstrated and a transoesophageal echocardiogram did not reveal vegetations. In the context of sepsis, the patient's INR initially increased to 3.7. Subsequently, his INR decreased despite dramatic increases in warfarin dosing up to 22mg. He was discharged home on IV flucloxacillin. 14 doses of low molecular weight heparin and an increase of 250% of warfarin (from 7mg to 17mg average) were necessary. It was only with close home monitoring that we were able to detect this significant interaction and prevent serious complications. <h3>Summary</h3> Flucloxacillin can reduce the anticoagulant effect of Vitamin K Antagonists. The literature about this interaction is scarce. One possible mechanism is induction of CYP3A4-mediated metabolism of R-warfarin by Flucloxacilin via Pregnane-X hormone receptor upregulation resulting in reduced warfarin concentrations and effects. This case report raises concerns about antibiotic therapy in VAD patients. It is important to be aware of this potentially serious interaction and close INR monitoring is recommended.