Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
Simone Mornese Pinna,
Silvia Corcione,
Amedeo De Nicolò,
Giorgia Montrucchio,
Silvia Scabini,
Davide Vita,
Ilaria De Benedetto,
Tommaso Lupia,
Jacopo Mula,
Giovanni Di Perri,
Antonio D’Avolio,
Francesco Giuseppe De Rosa
Affiliations
Simone Mornese Pinna
Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy
Silvia Corcione
Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy
Amedeo De Nicolò
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10126 Turin, Italy
Giorgia Montrucchio
Department of Anesthesia, Intensive Care and Emergency, Citta della Salute e della Scienza Hospital, University of Turin, 10124 Turin, Italy
Silvia Scabini
Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy
Davide Vita
Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy
Ilaria De Benedetto
Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy
Tommaso Lupia
ASL Asti, Cardinal Massaia Hospital, 14100 Asti, Italy
Jacopo Mula
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10126 Turin, Italy
Giovanni Di Perri
Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
Antonio D’Avolio
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10126 Turin, Italy
Francesco Giuseppe De Rosa
Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy
Background: Cefiderocol is a novel parenteral siderophore cephalosporin, demonstrating enhanced activity against multidrug-resistant (MDR) Gram-negative bacteria and difficult-to-treat Acinetobacter baumannii (DTR-AB). Plasma-free trough concentration (fCtrough) over the minimum inhibitory concentration (MIC) was reported as the best pharmacokinetic parameter to describe the microbiological efficacy of cefiderocol. Materials and methods: We retrospectively described the pharmacokinetic and pharmacodynamic profile of three critically ill patients admitted to the intensive care unit, receiving cefiderocol under compassionate use to treat severe DTR-AB infections while undergoing continuous venovenous haemofiltration. Cefiderocol was administrated at a dosage of 2 g every 8 h infused over 3 h. Therapeutic drug monitoring (TDM) was assessed at the steady state. Cthrough was evaluated by assuming a plasma protein binding of 58.0%. The fCmin/MIC was calculated assuming a cefiderocol MIC equal to the PK-PD breakpoint of susceptibility ≤ 2. The association between the PK/PD parameters and microbiological outcome was assessed. Results: fCtrough/MIC were >12 in 2 patients and 2.9 in the 1 who rapidly recovered from renal failure. Microbiological cure occurred in 3/3 of patients. None of the 3 patients died within 30 days. Conclusions: A cefiderocol dosage of 2 g q8 h in critically ill patients with AKI undergoing CVVH may bring about a very high plasma concentration, corresponding to essentially 100% free time over the MIC for DTR-AB.
