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Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series

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 (fC(trough)) over the minimum inhibitory concent...

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Autores principales: Mornese Pinna, Simone, Corcione, Silvia, De Nicolò, Amedeo, Montrucchio, Giorgia, Scabini, Silvia, Vita, Davide, De Benedetto, Ilaria, Lupia, Tommaso, Mula, Jacopo, Di Perri, Giovanni, D’Avolio, Antonio, De Rosa, Francesco Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774561/
https://www.ncbi.nlm.nih.gov/pubmed/36551485
http://dx.doi.org/10.3390/antibiotics11121830
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author Mornese Pinna, Simone
Corcione, Silvia
De Nicolò, Amedeo
Montrucchio, Giorgia
Scabini, Silvia
Vita, Davide
De Benedetto, Ilaria
Lupia, Tommaso
Mula, Jacopo
Di Perri, Giovanni
D’Avolio, Antonio
De Rosa, Francesco Giuseppe
author_facet Mornese Pinna, Simone
Corcione, Silvia
De Nicolò, Amedeo
Montrucchio, Giorgia
Scabini, Silvia
Vita, Davide
De Benedetto, Ilaria
Lupia, Tommaso
Mula, Jacopo
Di Perri, Giovanni
D’Avolio, Antonio
De Rosa, Francesco Giuseppe
author_sort Mornese Pinna, Simone
collection PubMed
description 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 (fC(trough)) 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: fC(trough)/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.
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spelling pubmed-97745612022-12-23 Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series Mornese Pinna, Simone Corcione, Silvia De Nicolò, Amedeo Montrucchio, Giorgia Scabini, Silvia Vita, Davide De Benedetto, Ilaria Lupia, Tommaso Mula, Jacopo Di Perri, Giovanni D’Avolio, Antonio De Rosa, Francesco Giuseppe Antibiotics (Basel) Article 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 (fC(trough)) 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: fC(trough)/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. MDPI 2022-12-16 /pmc/articles/PMC9774561/ /pubmed/36551485 http://dx.doi.org/10.3390/antibiotics11121830 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mornese Pinna, Simone
Corcione, Silvia
De Nicolò, Amedeo
Montrucchio, Giorgia
Scabini, Silvia
Vita, Davide
De Benedetto, Ilaria
Lupia, Tommaso
Mula, Jacopo
Di Perri, Giovanni
D’Avolio, Antonio
De Rosa, Francesco Giuseppe
Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
title Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
title_full Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
title_fullStr Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
title_full_unstemmed Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
title_short Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series
title_sort pharmacokinetic of cefiderocol in critically ill patients receiving renal replacement therapy: a case series
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774561/
https://www.ncbi.nlm.nih.gov/pubmed/36551485
http://dx.doi.org/10.3390/antibiotics11121830
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