Prolonged Versus Intermittent Infusion of ß-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models.
Clin Pharmacokinet
; 59(10): 1237-1250, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32710435
ABSTRACT
BACKGROUND:
Administering ß-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 ß-lactam antibiotics.METHODS:
The MEDLINE and EMBASE databases were searched. To compare the bactericidal action of ß-lactam antibiotics across different modes of infusion, the reported PK/PD outcomes, expressed as the percentage of time (T) that free (f) ß-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 ß-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 ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Beta-Lactamas
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Clin Pharmacokinet
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Bélgica