PK/PD modeling of daptomycin against MRSA and MRSE and Monte Carlo simulation for bacteremia treatment.
Bacteremia
Daptomycin
Monte Carlo simulation
PK/PD modeling
Journal
Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]
ISSN: 1678-4405
Titre abrégé: Braz J Microbiol
Pays: Brazil
ID NLM: 101095924
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
22
12
2020
accepted:
11
07
2021
pubmed:
3
8
2021
medline:
16
12
2021
entrez:
2
8
2021
Statut:
ppublish
Résumé
The aim of this study was to investigate the effect of daptomycin against methicillin-resistant staphylococci (MRSA and MRSE) bacteremia using computer modeling. A pharmacokinetic/pharmacodynamic (PK/PD) modeling strategy to explain the data from an in vitro dynamic model employing time-kill curves for MRSA and MRSE was proposed. Bacterial killing was followed over time by determining viable counts and the resulting time-kill data was analyzed. Monte Carlo simulations were performed using pharmacokinetic parameters and pharmacodynamic data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (MIC) targets of daptomycin. Simulations were conducted to assess the reduction in the number of colony-forming units (CFU)/mL for 18 days of treatment with daptomycin at doses of 6, 8, and 10 mg/kg/24 h or 48 h with variations in creatinine clearance (CL Monte Carlo simulations showed that for MRSA there was a reduction > 2 log CFU/mL with doses ≥ 6 mg/kg/day in 75th percentile of the simulated population after 18 days of treatment with daptomycin, whereas for MRSE this reduction was observed in 95th percentile of the population. The presented in vitro PK/PD model and associated modeling approach were able to characterize the time-kill kinetics of MRSA and MRSE. Our study based on PTAs suggests that doses ≥ 6 mg/kg/day of daptomycin should be used to treat bacteremia caused by MRSA and MRSE in patients with CL
Identifiants
pubmed: 34337679
doi: 10.1007/s42770-021-00582-4
pii: 10.1007/s42770-021-00582-4
pmc: PMC8578253
doi:
Substances chimiques
Anti-Bacterial Agents
0
Daptomycin
NWQ5N31VKK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1967-1979Informations de copyright
© 2021. Sociedade Brasileira de Microbiologia.
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