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Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
Simone Mornese Pinna1, Silvia Corcione1,2, Amedeo De Nicolò3
1Department of Medical Sciences, Infectious Diseases, University of Turin, 10126 Turin, Italy.
Abstract:
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.
Insights
Cefiderocol at 2g q8h achieved high plasma concentrations in critically ill patients with acute kidney injury undergoing continuous venovenous hemofiltration, leading to microbiological cure in all cases.
Area of Science:
- Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Cefiderocol is a novel siderophore cephalosporin effective against multidrug-resistant Gram-negative bacteria.
- It shows particular promise against difficult-to-treat Acinetobacter baumannii.
- Plasma-free trough concentration over minimum inhibitory concentration (fCtrough/MIC) is the key pharmacokinetic parameter for cefiderocol efficacy.
Purpose of the Study:
- To describe the pharmacokinetic and pharmacodynamic profile of cefiderocol in critically ill patients.
- To evaluate cefiderocol efficacy in severe infections caused by difficult-to-treat Acinetobacter baumannii (DTR-AB) in patients undergoing continuous venovenous hemofiltration (CVVH).
- To assess the association between pharmacokinetic/pharmacodynamic (PK/PD) parameters and microbiological outcomes.
Main Methods:
- Retrospective analysis of three critically ill patients receiving cefiderocol (2 g every 8 hours infused over 3 hours) for severe DTR-AB infections.
- Patients were undergoing continuous venovenous hemofiltration (CVVH).
- Therapeutic drug monitoring (TDM) was performed at steady state; fCtrough/MIC was calculated using a protein binding of 58.0% and MIC at the susceptibility breakpoint (≤2).
Main Results:
- fCtrough/MIC values exceeded 12 in two patients and were 2.9 in one patient who recovered from renal failure.
- All three patients (3/3) achieved microbiological cure.
- No 30-day mortality was observed in the study group.
Conclusions:
- A cefiderocol dosage of 2 g every 8 hours may achieve high plasma concentrations in critically ill patients with acute kidney injury (AKI) undergoing CVVH.
- This dosage regimen potentially ensures 100% of the dosing interval with free drug concentration above the MIC for DTR-AB.
- Cefiderocol appears to be a viable treatment option for severe DTR-AB infections in this challenging patient population.
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