Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU

Objective:To report the difficulty in achieving and maintaining target antibiotic exposure in critically ill patients with deepseeded infections. Case Summary: We present a case of a 36-year-old man who was admitted to the intensive care unit with diffuse central nervous system and peripheral methic...

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Main Authors:	Abdul Aziz, Mohd. Hafiz, McDonald, Craig, McWhinney, Brett, Ungerer , Jacobus P., Lipman, Jeffrey, Roberts, Jason A.
Format:	Article
Language:	English
Published:	Sage Publishing 2014
Subjects:	RM Therapeutics. Pharmacology RS Pharmacy and materia medica
Online Access:	http://irep.iium.edu.my/37917/ http://irep.iium.edu.my/37917/ http://irep.iium.edu.my/37917/1/Ann_Pharmacother-2014-Abdul-Aziz-1060028014540610.pdf

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recordtype	eprints
spelling	iium-379172018-06-19T06:45:28Z http://irep.iium.edu.my/37917/ Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU Abdul Aziz, Mohd. Hafiz McDonald, Craig McWhinney, Brett Ungerer , Jacobus P. Lipman, Jeffrey Roberts, Jason A. RM Therapeutics. Pharmacology RS Pharmacy and materia medica Objective:To report the difficulty in achieving and maintaining target antibiotic exposure in critically ill patients with deepseeded infections. Case Summary: We present a case of a 36-year-old man who was admitted to the intensive care unit with diffuse central nervous system and peripheral methicillin-sensitive Staphylococcus aureus infection (minimum inhibitory concentration; MIC, 1 μg/mL). Owing to the complicated nature of the infection, sequential concentrations of free flucloxacillin were measured in plasma and cerebrospinal fluid (CSF) and used to direct antibiotic dosing. Unsurprisingly, the trough plasma concentrations of flucloxacillin were below the MIC (0.2-0.4 μg/mL), and the corresponding CSF concentrations were undetectable (<0.1 μg/mL) with standard intermittent bolus dosing of 2 g every 4 hours. By administering flucloxacillin by continuous infusion (CI) and increasing the dose to 20 g daily, the plasma (2.2-5.7 μg/mL) and CSF (0.1 μg/mL) levels were increased, albeit lower than the predefined targets (plasma, 40 μg/mL; CSF, 4 μg/mL). Discussion: The presence of physiological changes associated with critical illness—namely, hypoalbuminemia and augmented renal clearance—may significantly alter antibiotic pharmacokinetics, and this phenomenon may lead to suboptimal antibiotic exposure if they are not accounted for. This case also highlights the value of applying CI in such patient groups and demonstrates the significance of monitoring plasma and CSF drug concentrations in optimizing antibiotic delivery. Conclusions: Future research should aim to evaluate the utility of such drug monitoring with regard to patient outcomes and cost-effectiveness. Sage Publishing 2014-06-20 Article PeerReviewed application/pdf en http://irep.iium.edu.my/37917/1/Ann_Pharmacother-2014-Abdul-Aziz-1060028014540610.pdf Abdul Aziz, Mohd. Hafiz and McDonald, Craig and McWhinney, Brett and Ungerer , Jacobus P. and Lipman, Jeffrey and Roberts, Jason A. (2014) Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU. Annals of Pharmacotherapy . pp. 1-5. ISSN 1542-6270 http://aop.sagepub.com/
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RM Therapeutics. Pharmacology RS Pharmacy and materia medica
spellingShingle	RM Therapeutics. Pharmacology RS Pharmacy and materia medica Abdul Aziz, Mohd. Hafiz McDonald, Craig McWhinney, Brett Ungerer , Jacobus P. Lipman, Jeffrey Roberts, Jason A. Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU
description	Objective:To report the difficulty in achieving and maintaining target antibiotic exposure in critically ill patients with deepseeded infections. Case Summary: We present a case of a 36-year-old man who was admitted to the intensive care unit with diffuse central nervous system and peripheral methicillin-sensitive Staphylococcus aureus infection (minimum inhibitory concentration; MIC, 1 μg/mL). Owing to the complicated nature of the infection, sequential concentrations of free flucloxacillin were measured in plasma and cerebrospinal fluid (CSF) and used to direct antibiotic dosing. Unsurprisingly, the trough plasma concentrations of flucloxacillin were below the MIC (0.2-0.4 μg/mL), and the corresponding CSF concentrations were undetectable (<0.1 μg/mL) with standard intermittent bolus dosing of 2 g every 4 hours. By administering flucloxacillin by continuous infusion (CI) and increasing the dose to 20 g daily, the plasma (2.2-5.7 μg/mL) and CSF (0.1 μg/mL) levels were increased, albeit lower than the predefined targets (plasma, 40 μg/mL; CSF, 4 μg/mL). Discussion: The presence of physiological changes associated with critical illness—namely, hypoalbuminemia and augmented renal clearance—may significantly alter antibiotic pharmacokinetics, and this phenomenon may lead to suboptimal antibiotic exposure if they are not accounted for. This case also highlights the value of applying CI in such patient groups and demonstrates the significance of monitoring plasma and CSF drug concentrations in optimizing antibiotic delivery. Conclusions: Future research should aim to evaluate the utility of such drug monitoring with regard to patient outcomes and cost-effectiveness.
format	Article
author	Abdul Aziz, Mohd. Hafiz McDonald, Craig McWhinney, Brett Ungerer , Jacobus P. Lipman, Jeffrey Roberts, Jason A.
author_facet	Abdul Aziz, Mohd. Hafiz McDonald, Craig McWhinney, Brett Ungerer , Jacobus P. Lipman, Jeffrey Roberts, Jason A.
author_sort	Abdul Aziz, Mohd. Hafiz
title	Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU
title_short	Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU
title_full	Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU
title_fullStr	Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU
title_full_unstemmed	Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU
title_sort	low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the icu
publisher	Sage Publishing
publishDate	2014
url	http://irep.iium.edu.my/37917/ http://irep.iium.edu.my/37917/ http://irep.iium.edu.my/37917/1/Ann_Pharmacother-2014-Abdul-Aziz-1060028014540610.pdf
first_indexed	2023-09-18T20:54:22Z
last_indexed	2023-09-18T20:54:22Z
_version_	1777410205487726592

Low flucloxacillin concentrations in a patient with central nervous system infection: the need for plasma and cerebrospinal fluid drug monitoring in the ICU

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