2434. Review of Linezolid (LZD) Use and Onset of Toxicity in 4 Belgian Hospital Centers: A Retrospective Study

Abstract

BackgroundLZD is approved (FDA label and Belgian Summary of Product Characteristics [SmPC]) for the treatment of SSSTI and pneumonia caused by Gram-positive organisms (mainly MRSA and VRE) only. Yet IDSA recommendations for MRSA infections also position LZD for osteomyelitis and as an alternative for CNS infections and bacteremia (CID 2011;52:e18–55). LZD use is limited by adverse events, the incidence of which may vary according to the length and conditions of therapy. The aim of this study was to document LZD actual use and onset of adverse events in real life clinical practice. MethodsObservational, retrospective study in 4 Belgian hospital centers (about 4,000 beds) over 1 year (2016). Analysis of medical files (222 treatments) to collect information on (i) patient’s characteristics and treatment modalities and indications, (ii) occurrence, causality and severity of adverse drug reactions (ADR), and (iii) concomitant medications (increasing the risk of developing a serotonin syndrome [SS]). ResultsKey data are shown in the figure. 18% of prescriptions matched the indications approved in the United States and in Belgium and 47% those mentioned in the IDSA recommendations. 54% of the patients were infected by bacteria resistant to first choice drugs. Decreases in platelet counts (DPC) were observed in 30% of patients (compared with <1% thrombocytopenia in the Belgian SmPC or 25% DPC in 3% of patients in FDA label) and was observed in 15/39 cases (patients with in-Belgian label indications), 35/105 cases (patients with IDSA indications), 30/117 (other indications). Treatment duration > 10 days was the only significant risk factor for DPC (Kaplan Meyer; P < 0.005 [Mann–Whitney]). 7 cases of CNS ADR were reported. Although 41% of patients were prescribed at least 1 drug increasing SS risk, SS was actually observed in only 1 patient. ConclusionLZD is mainly used in off-Belgian label indications, some of which, however, are in the IDSA recommendations. The high incidence of ADR (40%) as well as the frequent use of co-medications putting patients at risk of SS highlight the importance of follow-up for LZD-treated patients. A prospective study is now needed to better assess the severity of these ADR and identify more associated risk factors. Disclosures All authors: No reported disclosures.