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Cefiderocol Treatment for Severe Infections due to Difficult-to-Treat-Resistant Non-Fermentative Gram-Negative
Paul-Henri Wicky1, Joséphine Poiraud2,3, Manuel Alves2
1Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat Hospital, Paris Cité University, F-75018 Paris, France.
Abstract:
Cefiderocol (FDC) is a siderophore cephalosporin now recognized as a new weapon in the treatment of difficult-to-treat-resistant (DTR) Gram-negative pathogens, including carbapenemase-producing enterobacterales and non-fermentative Gram-negative bacilli (GNB). This article reports our experience with an FDC-based regimen in the treatment of 16 extremely severe patients (invasive mechanical ventilation, 15/16; extracorporeal membrane oxygenation, 9/16; and renal replacement therapy, 8/16) infected with DTR GNB. Our case series provides detailed insight into the pharmacokinetic profile and the microbiological data in real-life conditions. In the narrative review, we discuss the interest of FDC in the treatment of non-fermentative GNB in critically ill patients. We reviewed the microbiological spectrum, resistance mechanisms, pharmacokinetics/pharmacodynamics, efficacy and safety profiles, and real-world evidence for FDC. On the basis of our experience and the available literature, we discuss the optimal FDC-based regimen, FDC dosage, and duration of therapy in critically ill patients with DTR non-fermentative GNB infections.
Insights
Cefiderocol (FDC) offers a new treatment option for difficult-to-treat-resistant Gram-negative infections in critically ill patients. This case series details FDC
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Pharmacology
Background:
- Difficult-to-treat-resistant (DTR) Gram-negative pathogens pose a significant challenge in critically ill patients.
- Siderophore cephalosporins, like cefiderocol (FDC), represent a novel therapeutic approach.
Purpose of the Study:
- To report clinical experience with an FDC-based regimen in severely ill patients with DTR Gram-negative bacilli (GNB) infections.
- To review the literature on FDC for treating non-fermentative GNB in the intensive care unit.
Main Methods:
- Retrospective case series of 16 critically ill patients treated with FDC.
- Narrative literature review focusing on FDC's microbiological spectrum, resistance, PK/PD, efficacy, safety, and real-world data.
Main Results:
- Detailed pharmacokinetic and microbiological data from real-world FDC use in severe DTR GNB infections.
- Review of FDC's utility in non-fermentative GNB, including resistance mechanisms and clinical outcomes.
Conclusions:
- FDC demonstrates potential as a crucial agent against DTR Gram-negative infections in critical care settings.
- Discussion on optimizing FDC dosage, regimen, and duration for DTR non-fermentative GNB infections in critically ill patients.
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