Abstract

BackgroundTedizolid (TZD) is approved for acute bacterial skin and skin structure infections (ABSSSI), but often used for complicated infections to avoid linezolid (LZD) adverse events (AE), particularly when long-term treatment is indicated. This studied aimed to characterize the tolerability of TZD, including patients (pts) receiving prolonged treatment.MethodsRetrospective review of pts who received TZD > 72 hours. Thrombocytopenia was defined as a 50% decrease from baseline platelet count. Favorable clinical outcome was defined as completing therapy without an AE or hospital readmission within 30 days.Results86 pts accounting for 102 courses were included. Median age of pts was 57 years and 43% were immunocompromised. Median duration of TZD therapy was 8 days (range: 4 – 350) and 32% of courses were >14 days. Common indications were ABSSSI (n=42), bacteremia (n=15), intra-abdominal infection (n=11), and pneumonia (n=10). 47% and 5% of courses were associated with MRSA or VRE and M. abscessus, respectively. 44% of TZD courses were preceded by treatment failure or AE associated with alternative therapies. AEs attributed to LZD were documented in 13 patients: thrombocytopenia (n=11), lactic acidosis (n=1), or both (n=1). Serotonergic agents were administered during 76% of TZD courses; however, no patient developed serotonin syndrome. 8% of TZD courses were stopped prematurely due to AEs that included thrombocytopenia (n=3), gastrointestinal intolerance (n=2), confusion (n=1), eosinophilia (n=1) and thrombocytopenia with lactic acidosis (n=1). All cases of thrombocytopenia occurred in pts with baseline platelets < 100,000 cells/L. 79% of pts receiving > 14 days of TZD completed therapy successfully without AEs. Among pts who failed alternative therapies, 74% were able to tolerate TZD and completed therapy. Overall, 80% of courses were completed with a favorable outcome.Clinical Outcomes of Extended TZD Therapy ConclusionThe safety of prolonged TZD treatment is not well-described. In our experience, TZD was well-tolerated, including among pts who failed alternative therapy. No pt receiving concomitant serotonergic agents developed serotonin syndrome and thrombocytopenia occurred exclusively among pts with low baseline platelets. Treatment courses >14 days were not associated with an increase in the rate of AEs.Disclosures Rachel V. Marini, PharmD, Merck (Research Grant or Support) Ryan K. Shields, PharmD, MS, Allergan (Advisor or Review Panel member, Research Grant or Support)Entasis (Advisor or Review Panel member)Melinta (Research Grant or Support)Menarini (Consultant)Merck (Advisor or Review Panel member, Research Grant or Support)Shionogi (Advisor or Review Panel member, Research Grant or Support)Summit (Advisor or Review Panel member)Tetraphase (Research Grant or Support)Venatorx (Advisor or Review Panel member, Research Grant or Support)

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