Role of Cefiderocol in the Treatment of Carbapenem-Resistant Nonfermenting Gram-Negative Bacilli (Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia) Infections: An Expert Statement.

introductionInfections caused by nonfermenting gram-negative bacilli (NF-GNB), particularly Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, are associated with high morbidity and mortality, especially among critically ill or immunocompromised patients. The rise of multidrug resistance has rendered many first-line antibiotics ineffective, highlighting the need for novel agents such as cefiderocol, a siderophore cephalosporin with unique pharmacokinetics and broad in vitro activity against resistant gram-negative pathogens.

methodsA multidisciplinary panel of French experts in infectious diseases, microbiology, pharmacology, and intensive care reviewed the available evidence and clinical experience of cefiderocol. Using a structured consensus process, the group developed pragmatic, expert-based recommendations for its use against A. baumannii, S. maltophilia, and P. aeruginosa, considering clinical scenarios, resistance mechanisms, pharmacokinetic/pharmacodynamic (PK/PD) optimization, and practical implementation.

resultsCefiderocol demonstrates potent in vitro activity against NF-GNB, including colistin- and imipenem-resistant isolates. Clinical success, however, depends on optimized PK/PD exposure, particularly in high-inoculum infections or patients with augmented renal clearance. Cohort studies and meta-analyses suggest lower mortality and markedly reduced nephrotoxicity compared with colistin-based regimens in A. baumannii infections. For S. maltophilia, cefiderocol shows consistently low minimum inhibitory concentration (MIC) and serves as a reliable alternative to trimethoprim-sulfamethoxazole or fluoroquinolones. Against P. aeruginosa, it retains high in vitro activity and should be considered after failure of newer β-lactams, with caution in New Delhi metallo-β-lactamase (NDM)-producing isolates. Continuous infusion and early therapeutic drug monitoring are encouraged to maximize efficacy.

conclusionsCefiderocol is a valuable therapeutic option for severe NF-GNB infections when conventional agents fail. Its use should be guided by pathogen-specific MICs and PK/PD-based dosing. The expert panel underscores the importance of early microbiological diagnosis, susceptibility testing, and optimized administration to achieve maximal clinical benefit while preserving cefiderocol's role within antimicrobial stewardship.