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

Cefiderocol is an option for infections caused by multidrug-resistant Pseudomonas aeruginosa, but its in vitro activity against these isolates and its clinical effectiveness for isolates with MICs of >1 & mu;g/mL is unclear. We investigated the in vitro 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, & LE;1 & mu;g/mL) and Clinical and Laboratory Standards Institute (CLSI; susceptible, & LE;4 & mu;g/mL) cefiderocol breakpoints were applied. Additionally, molecular characterization of & beta;-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 & LE;1 & mu;g/mL, 69% (9/13) with a cefiderocol MIC of 2 to 4 & mu;g/mL, and 100% (4/4) with an MIC of & GE;8 & mu;g/mL, while day 28 all-cause mortality rates were 23% (6/26; MIC & LE; 1 & mu;g/mL), 33% (4/12; MIC, 2 to 4 & mu;g/mL), and 0% (0/4; MIC & GE;8 & mu;g/mL), respectively. Cefiderocol was active in vitro against most P. aeruginosa isolated from patients with limited or no alternative therapies. Patients with cefiderocol MICs of 2 to 4 & mu;g/mL did not have significantly worse outcomes than those with MICs of & LE;1 & mu;g/mL. Cefiderocol is an option for infections caused by multidrug-resistant Pseudomonas aeruginosa, but its in vitro activity against these isolates and its clinical effectiveness for isolates with MICs of >1 & mu;g/mL is unclear. We investigated the in vitro 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.

Automated summary

Cefiderocol is a potential treatment option for infections caused by multidrug-resistant Pseudomonas aeruginosa, especially for isolates with limited or no alternative therapies. However, its effectiveness for isolates with higher MIC values (>1 μg/mL) remains uncertain.