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Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR...

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Autores principales: Ehrentraut, Stefan Felix, Muenster, Stefan, Kreyer, Stefan, Theuerkauf, Nils Ulrich, Bode, Christian, Steinhagen, Folkert, Ehrentraut, Heidi, Schewe, Jens-Christian, Weber, Matthias, Putensen, Christian, Muders, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143967/
https://www.ncbi.nlm.nih.gov/pubmed/32183443
http://dx.doi.org/10.3390/microorganisms8030415
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author Ehrentraut, Stefan Felix
Muenster, Stefan
Kreyer, Stefan
Theuerkauf, Nils Ulrich
Bode, Christian
Steinhagen, Folkert
Ehrentraut, Heidi
Schewe, Jens-Christian
Weber, Matthias
Putensen, Christian
Muders, Thomas
author_facet Ehrentraut, Stefan Felix
Muenster, Stefan
Kreyer, Stefan
Theuerkauf, Nils Ulrich
Bode, Christian
Steinhagen, Folkert
Ehrentraut, Heidi
Schewe, Jens-Christian
Weber, Matthias
Putensen, Christian
Muders, Thomas
author_sort Ehrentraut, Stefan Felix
collection PubMed
description (1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.
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spelling pubmed-71439672020-04-13 Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks Ehrentraut, Stefan Felix Muenster, Stefan Kreyer, Stefan Theuerkauf, Nils Ulrich Bode, Christian Steinhagen, Folkert Ehrentraut, Heidi Schewe, Jens-Christian Weber, Matthias Putensen, Christian Muders, Thomas Microorganisms Article (1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients. MDPI 2020-03-15 /pmc/articles/PMC7143967/ /pubmed/32183443 http://dx.doi.org/10.3390/microorganisms8030415 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ehrentraut, Stefan Felix
Muenster, Stefan
Kreyer, Stefan
Theuerkauf, Nils Ulrich
Bode, Christian
Steinhagen, Folkert
Ehrentraut, Heidi
Schewe, Jens-Christian
Weber, Matthias
Putensen, Christian
Muders, Thomas
Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks
title Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks
title_full Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks
title_fullStr Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks
title_full_unstemmed Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks
title_short Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks
title_sort extensive therapeutic drug monitoring of colistin in critically ill patients reveals undetected risks
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143967/
https://www.ncbi.nlm.nih.gov/pubmed/32183443
http://dx.doi.org/10.3390/microorganisms8030415
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