638. The Impact of <i>in vitro</i> Synergy Between Colistin and Meropenem on Clinical Outcomes in Invasive Carbapenem-resistant Gram-negative Infections: A Report from the OVERCOME Trial

Abstract Background Consensus guidelines caution against colistin (COL) monotherapy due to efficacy and resistance development concerns. The COL + meropenem (MEM) combination often displays in vitro synergy carbapenem-resistant (CR) Gram-negative bacilli (GNB). We recently completed a clinical trial comparing outcomes patients receiving vs. MEM. Herein we assess if, amongst MEM, differed as function of the presence (or absence) index pathogen. Methods OVERCOME was an international, multicenter, randomized, double-blind, placebo-controlled study placebo MEM for treatment pneumonia and/or bloodstream infection (BSI) CR GNB. Baseline isolates were susceptible (MIC ≤ 2 mg/L) underwent testing 24-hour time kill experiments (TKE). Synergy defined &amp;gt;2-log CFU/ml reduction with therapy compared most active single agent. Outcomes assessed included 28-day mortality, failure, ≥ 4 both overall cohort subgroup A. baumannii. Results Of 211 who received OVERCOME, 186 had baseline performed eligible this analysis. median age 70 years, 35% female, 48% white, 44% Asian. Sixty-eight percent intensive care unit (ICU) at onset. baumannii common pathogen (78%) (68%). demonstrated (76%). characteristics, clinical, microbiological similar infected which those where no (Table 1). In infections, associated decrease failure (53% 79%; p = 0.04). No significant impact on mortality or 2). Conclusion via TKE treated invasive infections Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Michael J. Rybak, MPH, PhD, Paratek Pharmaceuticals (Research Grant Support) Emmanuel Roilides, MD, FIDSA, FAAM, FESCMID, Sharp &amp; Dohme Corp. (Consultant, Grant/Research Matthew Sims, Astra Zeneca (Independent Contractor)Diasorin Molecular Contractor)Epigenomics Inc Contractor)Finch Contractor)Genentech Contractor)Janssen NV Contractor)Kinevant Sciences gmBH Contractor)Leonard-Meron Biosciences Contractor)Merck Co Contractor)OpGen Contractor)Prenosis Contractor)Regeneron Contractor)Seres Contractor)Shire Contractor)Summit Contractor)