dc.contributor.author | Dhaese, Sofie | |
dc.contributor.author | Heffernan, Aaron | |
dc.contributor.author | Liu, David | |
dc.contributor.author | Abdul-Aziz, Mohd Hafiz | |
dc.contributor.author | Stove, Veronique | |
dc.contributor.author | Tam, Vincent H | |
dc.contributor.author | Lipman, Jeffrey | |
dc.contributor.author | Roberts, Jason A | |
dc.contributor.author | De Waele, Jan J | |
dc.date.accessioned | 2020-08-04T04:22:03Z | |
dc.date.available | 2020-08-04T04:22:03Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0312-5963 | |
dc.identifier.doi | 10.1007/s40262-020-00919-6 | |
dc.identifier.uri | http://hdl.handle.net/10072/396153 | |
dc.description.abstract | Background: Administering β-lactam antibiotics via prolonged infusions for critically ill patients is mainly based on preclinical evidence. Preclinical data on this topic have not been systematically reviewed before.
Objectives: The aim of this study was to describe the pharmacokinetic/pharmacodynamic (PK/PD) indices and targets reported in preclinical models and to compare the bactericidal efficacy of intermittent and prolonged infusions of β-lactam antibiotics.
Methods: The MEDLINE and EMBASE databases were searched. To compare the bactericidal action of β-lactam antibiotics across different modes of infusion, the reported PK/PD outcomes, expressed as the percentage of time (T) that free (f) β-lactam antibiotic concentrations remain above the minimal inhibitory concentration (MIC) (%fT>MIC) or trough concentration (Cmin)/MIC of individual studies, were recomputed relative to the area under the curve of free drug to MIC ratio (fAUC24/MIC). A linear mixed-effects meta-regression was performed to evaluate the impact of the β-lactam class, initial inoculum, Gram stain, in vivo or in vitro experiment and mode of infusion on the reduction of bacterial cells (in colony-forming units/mL).
Results: Overall, 33 articles were included for review, 11 of which were eligible for meta-regression. For maximal bactericidal activity, intermittent experiments reported a PK/PD target of 40–70% fT>MIC, while continuous experiments reported a steady-state concentration to MIC ratio of 4–8. The adjusted effect of a prolonged as opposed to intermittent infusion on bacterial killing was small (coefficient 0.66, 95% confidence interval − 0.78 to 2.11).
Conclusions: Intermittent and prolonged infusions of β-lactam antibiotics require different PK/PD targets to obtain the same level of bacterial cell kill. The additional effect of a prolonged infusion for enhancing bacterial killing could not be demonstrated. | |
dc.description.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartofjournal | Clinical Pharmacokinetics | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearchcode | 3214 | |
dc.title | Prolonged Versus Intermittent Infusion of β-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Dhaese, S; Heffernan, A; Liu, D; Abdul-Aziz, MH; Stove, V; Tam, VH; Lipman, J; Roberts, JA; De Waele, JJ, Prolonged Versus Intermittent Infusion of β-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models, Clinical Pharmacokinetics, 2020 | |
dc.date.updated | 2020-08-04T03:51:46Z | |
gro.description.notepublic | This publication has been entered into Griffith Research Online as an Advanced Online Version. | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Heffernan, Aaron J. | |