Pharmacological and clinical profile of cefiderocol, a siderophore cephalosporin against gram-negative pathogens

Introduction: Increasing resistance of gram-negative bacteria poses a serious threat to global health. Thus, efficacious and safe antibiotics against resistant pathogens are urgently needed. Cefiderocol, a siderophore cephalosporin, addresses this unmet need. Areas covered: For this article, we screened all preclinical and clinical studies on cefiderocol published by January 2021 on PubMed. Also, regulatory documents, recent conference contributions, and selected data of antibiotic competitors are reviewed. We provide a comprehensive overview of the mode of action, in vitro and in vivo activity, pharmacokinetics/pharmacodynamics, and human pharmacokinetics. Last, we discuss the efficacy and safety data from the pivotal trials. Expert opinion: Cefiderocol was in vitro potent against virtually all gram-negative pathogens and resistance was rare. The target site pharmacokinetics (i.e. urinary and lung penetration) have been well described in humans and important PK/PD targets were reached. In the clinical trials, cefiderocol was non-inferior to carbapenems in the treatment of complicated urinary tract infections and nosocomial pneumonia. Against carbapenem-resistant gram-negative pathogens, cefiderocol was similar to the best available therapy, which was mainly based on the backbone agent colistin. Overall, a substantial body of evidence supports the clinical use of cefiderocol in patients with gram-negative infections and limited treatment options.

Automated summary

The increasing resistance of gram-negative bacteria necessitates effective antibiotics, and Cefiderocol, a siderophore cephalosporin, offers a promising solution in combating resistant pathogens. Comprehensive studies have shown its efficacy against various gram-negative pathogens with limited resistance, making it a viable treatment option for patients with gram-negative infections. In clinical trials, Cefiderocol demonstrated non-inferiority in treating complicated urinary tract infections and nosocomial pneumonia compared to carbapenems, and showed similarity in efficacy against carbapenem-resistant gram-negative pathogens when compared to the best available therapy.