# P-1353. Earlier Cefiderocol Use was Associated with Better Outcomes for Challenging Gram-Negative Bacterial Infections: US Results From the Global Observational PROVE Study

## TL;DR

Earlier use of cefiderocol in treating serious Gram-negative infections in the US was linked to better patient outcomes, especially when used before clinical decline.

## Contribution

This study provides new evidence that earlier administration of cefiderocol improves clinical outcomes in patients with challenging Gram-negative infections.

## Key findings

- Clinical cure rates were higher when cefiderocol was used empirically (73.7%) or for documented infections (72.3%) compared to salvage therapy (54.3%).
- Patients with respiratory tract infections had a 64.7% clinical cure rate and a 25.7% 30-day mortality rate.
- Cefiderocol was used in 33.1% of cases as combination therapy and for a median duration of 10 days.

## Abstract

The PROVE study enrolled 508 patients in the USA with serious Gram-negative bacterial infections treated with cefiderocol in routine clinical practice. The clinical outcomes of this subset of patients were assessed.

PROVE was an international, retrospective, observational medical chart review study (November 2020–July 2024). Data were analyzed from hospitalized US patients with confirmed Gram-negative bacterial infections, who received cefiderocol for the first time for ≥72 hours. Baseline demographics, clinical characteristics, cefiderocol use, clinical response, clinical cure, and all-cause mortality (ACM) were assessed.

Median (interquartile range [IQR]) age of patients was 58 (44–67) years and 61.2% were men (Table 1). The three most frequent concomitant conditions were diabetes mellitus (36.0%), chronic pulmonary disease (25.0%), and sepsis/septic shock (23.2%). Cefiderocol was given for a median (IQR) of 10 (7–16) days and as combination therapy in 33.1% of patients. At cefiderocol initiation, 57.3% of patients were in the intensive care unit and 47.6% were receiving organ support. Most patients (93.3%) had ≥1 risk factor for acquiring carbapenem-resistant (CR) Gram-negative bacteria. Respiratory tract infection (RTI) was the most common infection (n=272; 53.5%), followed by skin and skin structure infection (n=74; 14.6%) (Table 2). Overall rates of clinical cure, clinical response, and 30-day ACM were 70.1%, 77.8%, and 20.7%, respectively. Among patients with RTIs, clinical cure and 30-day ACM rates were 64.7% and 25.7%, respectively. Clinical cure rates were 73.7% (95% CI: 62.3–85.1%) when cefiderocol was used empirically and 72.3% (95% CI: 67.7–76.8%) when used for documented infections, whereas clinical cure rate was 54.3% (95% CI: 42.6–66.0%) when used as salvage therapy. Clinical cure rates for patients with Enterobacterales and Pseudomonas aeruginosa infections were 79.3% and 70.4%, with respective 30-day ACM rates of 17.2% and 20.4%.

US patients at risk for acquiring CR infections receiving cefiderocol as salvage therapy had a lower clinical cure rate than those treated empirically or for documented infections; thus, earlier cefiderocol treatment prior to clinical decline may be beneficial for such patients.

Cornelius J. Clancy, MD, Merck: Grant/Research Support|Shionogi: Advisor/Consultant Anne Lachiewicz, MD, MPH, Basilea: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support 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