P-1354. Outcomes of Patients Treated With Cefiderocol For Infections Caused by β-Lactam–β-Lactamase Inhibitor Non-Susceptible Bacteria: Subgroup Analysis of the PROVE Study

Abstract Background In vitro datiderocol and newly developed β-lactam–β-lactamase inhibitors (BL–BLIs). The PROVE study enrolled patients with serious Gram-negative bacterial infections treated with cefiderocol. We compared patient characteristics, pathogens, and clinical outcomes by susceptibility status to BL–BLIs. Methods PROVE was an observational medical chart review study (November 2020–July 2024). Data from hospitalized patients with confirmed Gram-negative bacterial infections and known BL–BLI susceptibility who received cefiderocol for ≥72 hours were included. Susceptible bacteria were susceptible to all BL–BLIs tested (S); non-susceptible bacteria were resistant or intermediate to at least one BL–BLIs tested (NS): ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam. Baseline demographics, clinical characteristics, and clinical outcomes were assessed. Results Among 504 patients, those infected by NS (N=382) vs S (N=122) bacteria were older (median age 62.0 vs 56.0 years, respectively; Table 1). Proportionally, fewer patients with NS vs S bacteria had indicators of more severe disease at cefiderocol initiation (intensive care unit stay: 52.6% vs 67.2%; organ support: 39.8% vs 51.6%). Patients with S vs NS pathogens more frequently had respiratory tract infections (71.3% vs 49.2%; Table 1) and were more likely to have ≥2 risk factors for acquired CR Gram-negative bacteria (66.4% vs 58.9%; Table 2). Polymicrobial infections were more common in patients with S vs NS bacteria (45.1% vs 25.1%, respectively). Nearly all NS bacteria were carbapenem resistant. Clinical cure rates were similar in patients with NS and S bacteria (70.2% vs 70.5%, respectively). 30-day all-cause mortality was numerically lower for patients with S vs NS bacteria (18.9% vs 23.6%, respectively) (Table 2). Conclusion Clinical cure rates were similar in patients with BL–BLI-S and NS pathogens, but differences in baseline severity limit comparability. Further analyses are needed to clarify the role of cefiderocol in infections caused by NS pathogens. Disclosures Mathias W. Pletz, MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Maria Cruz Soriano Cuesta, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Mundipharma: Advisor/Consultant|Mundipharma: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Viatris: Advisor/Consultant|Viatris: Honoraria Stefano Verardi, MD, Shionogi BV: Employee Karan Gill, Master of Science, Shionogi BV: Employee Anne Santerre Henriksen, PHD, Shionogi BV: Advisor/Consultant Sean T. Nguyen, PharmD, Shionogi Inc: Employee