2246. Improved Outcomes for Cancer Patients Treated With Ceftazidime–Avibactam vs. Polymyxin-Containing Regimens for Carbapenem-Resistant Enterobacteriaceae Bacteremia

Abstract Background Outcomes are improved with ceftazidime–avibactam (CZA) compared with polymyxin-based regimens (PBR) for carbapenemase-producing carbapenem-resistant Enterobacteriaceae. It is unclear whether this finding is true in non-carbapenemase (non-CP) producing CRE. The purpose of this study was to compare the efficacy and safety of CZA-based and PBR for CRE bacteremia in cancer patients with a high prevalence of non-CP CRE. Methods Adult cancer patients with first occurrence of CRE (i.e., meropenem non-susceptible) bacteremia treated with either CZA or PBR as directed therapy were included. Day 14 integrated benefit-risk outcomes based on desirability of outcome ranking (DOOR; (1) cured and discharged home, (2) cured and hospitalized, (3) cured and hospitalized with renal failure, (4) not cured, (5) dead) were used. DOOR is a recently developed statistical approach designed to unify important patient and clinician outcomes. Inverse probability of treatment weighted (IPTW) ordered logistic regression was used to model the odds of moving down ranked DOOR categories (i.e., having a worse outcome). The probability of a patient treated with CZA or a PBR having a worse DOOR category was also calculated. IPTW logistic regression was used to model the odds of 14-day mortality. Results 43 patients (CZA, n = 24; PBR, n = 19) with similar demographics and relative illness were included. Klebsiella pneumoniae (n = 21) and Escherichia coli (n = 16) were most common. 16/43 (37%) were CP CRE, 19/43 (44%) were non-CP CRE, and the remainder were unknown. The probability of a better DOOR for patients treated with CZA was 58% (95% CI 53% - 62%). Patients treated with CZA had an 81% reduction in IPTW-adjusted odds of a worse DOOR (OR 0.19, 95% CI 0.05 – 0.76; P = 0.02). 14-day mortality was 2/24 (8%) for patients receiving CZA vs. 5/19 (26%) for patients treated with PBR (IPTW-adjusted OR 0.12, 95% CI 0.02 – 0.82, P = 0.03). Conclusion These data suggest that CZA-based treatment, compared with PBR, has a superior integrated benefit-risk profile for the treatment of CRE bacteremia in cancer patients with a high burden of non-CP CRE. These findings build upon available data and suggest that CZA is preferred to PBR for CRE with heterogenous resistance mechanisms. Disclosures Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.