There is an increasing use of left ventricular assist devices (LVADs) as bridge to transplantation or permanent destination therapy in the heart failure patient population. Infection remains a common complication in LVADs, with Gram-positive skin flora as predominant pathogens implicated, including Staphylococcus aureus. While there is emerging evidence for synergistic antibiotic combinations with methicillin resistant Staphylococcus aureus, there remains a significant gap in the literature for persistent methicillin susceptible Staphylococcus aureus (MSSA) bacteremia. In this article, we describe the first successful treatment of persistent LVAD-related bacteremia with salvage oxacillin plus ertapenem. The salvage therapy described here must be balanced by the risks for toxicity, impact on resistance, microbiota disruption, drug shortages, and patient costs. This combination warrants further evaluation in the clinical setting to better establish its role in our expanding patient population.