Show simple item record

dc.contributor.authorDhaese, Sofie
dc.contributor.authorHeffernan, Aaron
dc.contributor.authorLiu, David
dc.contributor.authorAbdul-Aziz, Mohd Hafiz
dc.contributor.authorStove, Veronique
dc.contributor.authorTam, Vincent H
dc.contributor.authorLipman, Jeffrey
dc.contributor.authorRoberts, Jason A
dc.contributor.authorDe Waele, Jan J
dc.date.accessioned2020-08-04T04:22:03Z
dc.date.available2020-08-04T04:22:03Z
dc.date.issued2020
dc.identifier.issn0312-5963
dc.identifier.doi10.1007/s40262-020-00919-6
dc.identifier.urihttp://hdl.handle.net/10072/396153
dc.description.abstractBackground: 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.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.relation.ispartofjournalClinical Pharmacokinetics
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3214
dc.titleProlonged Versus Intermittent Infusion of β-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationDhaese, 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.updated2020-08-04T03:51:46Z
gro.description.notepublicThis publication has been entered into Griffith Research Online as an Advanced Online Version.
gro.hasfulltextNo Full Text
gro.griffith.authorHeffernan, Aaron J.


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record