Treatment of carbapenem-resistant Pseudomonas aeruginosa infections: a case for cefiderocol

Introduction Carbapenem-resistant (CR) Pseudomonas aeruginosa infections constitute a serious clinical threat globally. Patients are often critically ill and/or immunocompromised. Antibiotic options are limited and are currently centered on beta-lactam-beta-lactamase inhibitor (BL-BLI) combinations and the siderophore cephalosporin cefiderocol. Areas covered This article reviews the mechanisms of P. aeruginosa resistance and their potential impact on the activity of current treatment options, along with evidence for the clinical efficacy of BL-BLI combinations in P. aeruginosa infections, some of which specifically target infections due to CR organisms. The preclinical and clinical evidence supporting cefiderocol as a treatment option for P. aeruginosa involving infections is also reviewed. Expert opinion Cefiderocol is active against most known P. aeruginosa mechanisms mediating carbapenem resistance. It is stable against different serine- and metallo-beta-lactamases, and, due to its iron channel-dependent uptake mechanism, is not impacted by porin channel loss. Furthermore, the periplasmic level of cefiderocol is not affected by upregulated efflux pumps. The potential for on-treatment resistance development currently appears to be low, although more clinical data are required. Information from surveillance programs, real-world compassionate use, and clinical studies demonstrate that cefiderocol is an important treatment option for CR P. aeruginosa infections.