Prolonged Versus Intermittent Infusion of β-Lactam Antibiotics : A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Clinical pharmacokinetics - 59(2020), 10 vom: 24. Okt., Seite 1237-1250 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dhaese, Sofie [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 21.09.2021 Date Revised 21.09.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1007/s40262-020-00919-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312863810 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Systematic Review | |
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| 650 | 7 | |a beta-Lactams |2 NLM | |
| 700 | 1 | |a Heffernan, Aaron |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, David |e verfasserin |4 aut | |
| 700 | 1 | |a Abdul-Aziz, Mohd Hafiz |e verfasserin |4 aut | |
| 700 | 1 | |a Stove, Veronique |e verfasserin |4 aut | |
| 700 | 1 | |a Tam, Vincent H |e verfasserin |4 aut | |
| 700 | 1 | |a Lipman, Jeffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Roberts, Jason A |e verfasserin |4 aut | |
| 700 | 1 | |a De Waele, Jan J |e verfasserin |4 aut | |
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