Cefiderocol Treatment for Patients with Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa Infections in the Compassionate Use Program

• Published in: Antimicrobial agents and chemotherapy Vol. 67; no. 7; p. e0019423
• Main Authors: Satlin, Michael J, Simner, Patricia J, Slover, Christine M, Yamano, Yoshinori, Nagata, Tsutae D, Portsmouth, Simon
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 18.07.2023
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Carbapenems - pharmacology; Carbapenems - therapeutic use; Cefiderocol; Ceftazidime - pharmacology; Cephalosporins - pharmacology; Cephalosporins - therapeutic use; Clinical Therapeutics; Compassionate Use Trials; Drug Resistance, Multiple, Bacterial - genetics; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections - drug therapy; cefiderocol; clinical response; susceptibility breakpoint; carbapenem-resistant Pseudomonas aeruginosa; compassionate use
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.00194-23

Cefiderocol is an option for infections caused by multidrug-resistant Pseudomonas aeruginosa, but its activity against these isolates and its clinical effectiveness for isolates with MICs of >1 μg/mL is unclear. We investigated the activity of cefiderocol against P. aeruginosa isolates collected from patients treated with cefiderocol through the compassionate use program and assessed physician-reported clinical response and 28-day all-cause mortality by cefiderocol MIC values. P. aeruginosa isolates underwent susceptibility testing to cefiderocol and comparator agents by using reference broth microdilution. U.S. Food and Drug Administration (FDA; susceptible, ≤1 μg/mL) and Clinical and Laboratory Standards Institute (CLSI; susceptible, ≤4 μg/mL) cefiderocol breakpoints were applied. Additionally, molecular characterization of β-lactamase genes was performed. Clinical response and vital status were reported by treating physicians. Forty-six patients with P. aeruginosa infections were evaluated. Twenty-nine (63%) and 42 (91%) isolates were susceptible to cefiderocol using FDA and CLSI breakpoints, respectively. Thirty-seven (80%) and 32 (70%) isolates were not susceptible to ceftolozane-tazobactam and ceftazidime-avibactam, respectively. The clinical response rate was 69% (20/29) with a cefiderocol MIC of ≤1 μg/mL, 69% (9/13) with a cefiderocol MIC of 2 to 4 μg/mL, and 100% (4/4) with an MIC of ≥8 μg/mL, while day 28 all-cause mortality rates were 23% (6/26; MIC ≤ 1 μg/mL), 33% (4/12; MIC, 2 to 4 μg/mL), and 0% (0/4; MIC ≥8 μg/mL), respectively. Cefiderocol was active against most P. aeruginosa isolated from patients with limited or no alternative therapies. Patients with cefiderocol MICs of 2 to 4 μg/mL did not have significantly worse outcomes than those with MICs of ≤1 μg/mL.