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

TL;DR

This study analyzed outcomes of patients treated with cefiderocol for infections caused by bacteria resistant to beta-lactam-beta-lactamase inhibitors.

Contribution

The study provides clinical data on cefiderocol's effectiveness against non-susceptible bacteria in real-world settings.

Findings

Clinical cure rates were similar for patients infected with susceptible and non-susceptible bacteria.

Patients infected with non-susceptible bacteria were older and had less severe disease indicators at treatment initiation.

30-day mortality was numerically higher in patients with non-susceptible bacteria, though differences in baseline severity limit direct comparison.

Abstract

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.

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.

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).

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.

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

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