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

open forum infectious diseases

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

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