Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal

Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by in...

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Main Authors:	Osthoff, Michael, Siegemund, Martin, Balestra, Gianmarco, Abdul Aziz, Mohd. Hafiz, Roberts, Jason A.
Format:	Article
Language:	English English English
Published:	EMH Swiss Medical Publishers Ltd 2016
Subjects:	RM Therapeutics. Pharmacology RS Pharmacy and materia medica
Online Access:	http://irep.iium.edu.my/52327/ http://irep.iium.edu.my/52327/ http://irep.iium.edu.my/52327/ http://irep.iium.edu.my/52327/1/smw-2016-14368.pdf http://irep.iium.edu.my/52327/7/52327-Prolonged%20administration%20of%20%CE%B2-lactam%20antibiotics_SCOPUS.pdf http://irep.iium.edu.my/52327/8/52327-Prolonged%20administration%20of%20%CE%B2-lactam%20antibiotics_WOS.pdf

id	iium-52327
recordtype	eprints
spelling	iium-523272017-10-21T10:49:12Z http://irep.iium.edu.my/52327/ Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal Osthoff, Michael Siegemund, Martin Balestra, Gianmarco Abdul Aziz, Mohd. Hafiz Roberts, Jason A. RM Therapeutics. Pharmacology RS Pharmacy and materia medica Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates.The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for “prime time”, as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patientcentred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care. EMH Swiss Medical Publishers Ltd 2016-10-10 Article PeerReviewed application/pdf en http://irep.iium.edu.my/52327/1/smw-2016-14368.pdf application/pdf en http://irep.iium.edu.my/52327/7/52327-Prolonged%20administration%20of%20%CE%B2-lactam%20antibiotics_SCOPUS.pdf application/pdf en http://irep.iium.edu.my/52327/8/52327-Prolonged%20administration%20of%20%CE%B2-lactam%20antibiotics_WOS.pdf Osthoff, Michael and Siegemund, Martin and Balestra, Gianmarco and Abdul Aziz, Mohd. Hafiz and Roberts, Jason A. (2016) Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal. Swiss Medical Weekly, 146. w14368-1-w14368-13. ISSN 1424-3997 E-ISSN 1424-3997 file:///C:/Users/user/Downloads/smw-2016-14368.pdf :10.4414/smw.2016.14368
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	RM Therapeutics. Pharmacology RS Pharmacy and materia medica
spellingShingle	RM Therapeutics. Pharmacology RS Pharmacy and materia medica Osthoff, Michael Siegemund, Martin Balestra, Gianmarco Abdul Aziz, Mohd. Hafiz Roberts, Jason A. Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal
description	Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates.The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for “prime time”, as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patientcentred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care.
format	Article
author	Osthoff, Michael Siegemund, Martin Balestra, Gianmarco Abdul Aziz, Mohd. Hafiz Roberts, Jason A.
author_facet	Osthoff, Michael Siegemund, Martin Balestra, Gianmarco Abdul Aziz, Mohd. Hafiz Roberts, Jason A.
author_sort	Osthoff, Michael
title	Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal
title_short	Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal
title_full	Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal
title_fullStr	Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal
title_full_unstemmed	Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal
title_sort	prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal
publisher	EMH Swiss Medical Publishers Ltd
publishDate	2016
url	http://irep.iium.edu.my/52327/ http://irep.iium.edu.my/52327/ http://irep.iium.edu.my/52327/ http://irep.iium.edu.my/52327/1/smw-2016-14368.pdf http://irep.iium.edu.my/52327/7/52327-Prolonged%20administration%20of%20%CE%B2-lactam%20antibiotics_SCOPUS.pdf http://irep.iium.edu.my/52327/8/52327-Prolonged%20administration%20of%20%CE%B2-lactam%20antibiotics_WOS.pdf
first_indexed	2023-09-18T21:14:08Z
last_indexed	2023-09-18T21:14:08Z
_version_	1777411448491737088

Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal

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