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Introduction <p>Infections caused by nonfermenting gram-negative bacilli (NF-GNB), particularly <i>Acinetobacter baumannii</i>, <i>Stenotrophomonas maltophilia</i>, and <i>Pseudomonas aeruginosa</i>, 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.</p> Methods <p>A 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 <i>A. baumannii</i>, <i>S. maltophilia</i>, and <i>P. aeruginosa</i>, considering clinical scenarios, resistance mechanisms, pharmacokinetic/pharmacodynamic (PK/PD) optimization, and practical implementation.</p> Results <p>Cefiderocol 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 <i>A. baumannii</i> infections. For <i>S. maltophilia</i>, cefiderocol shows consistently low minimum inhibitory concentration (MIC) and serves as a reliable alternative to trimethoprim–sulfamethoxazole or fluoroquinolones. Against <i>P. aeruginosa</i>, 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.</p> Conclusions <p>Cefiderocol 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.</p>

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

  • 期刊论文

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  • 发表日期：

    2026年1月31日

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  • Alexandre Bleibtreu,
  • Youssef Bennis,
  • Aurélien Dinh,
  • Hervé Dupont,
  • Arnaud Friggeri,
  • Katy Jeannot,
  • Eric Kipnis,
  • Jean-Ralph Zahar

摘要

Introduction

Infections 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.

Methods

A 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.

Results

Cefiderocol 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.

Conclusions

Cefiderocol 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.