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Time-kill curves of daptomycin and Monte Carlo simulation for the treatment of bacteraemia caused by Enterococcus faecium

  • Bruna Kochhann Menezes
  • Izabel Almeida Alves
  • Keli Jaqueline Staudt
  • Betina Montanari Beltrame
  • Letícia Venz
  • Lessandra Michelin
  • Bibiana Verlindo Araujo
  • Leandro TassoEmail author
Clinical Microbiology - Research Paper
  • 18 Downloads

Abstract

Objectives

The aim of this study was to investigate the effect of daptomycin against vancomycin-resistant Enterococcus faecium bacteraemia using computer modelling.

Methods

Data obtained in vitro from time-kill curves were evaluated by PK/PD modelling and Monte Carlo simulations to determine the logarithmic reduction in the number of colony-forming units (CFU)/mL over 18 days of daptomycin treatment at 6, 8, and 10 mg/kg doses every 24 or 48 h and with variations in creatinine clearance (CLCR) of 15–29, 30–49, and 50–100 mL/min/1.73 m2. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for an area under the unbound drug concentration-time curve/minimum inhibitory concentration (fAUC/MIC) > 36 at the same doses and CLCR.

Results

Static time-kill model was employed to investigate the antibacterial efficacy of constant daptomycin concentrations. The time-kill curve analysis was performed using mathematical modelling based on a Hill coefficient factor. There was an expressive reduction (> 2 Log CFU/mL) over 18 days of daptomycin treatment in 75th percentile of individuals with CLCR of 15–100 mL/min/1.73 m2) with daptomycin 6–10 mg/kg/day, except for daptomycin every 48 h. Using fAUC/MIC > 36, PTA was > 90% at MICs ≤ 2 μg/mL.

Conclusions

Higher daptomycin doses were associated with higher mortality in time-kill curves. The simulations indicated that independent of the CLCR the therapeutic responses of VRE occur with doses of daptomycin ≥ 6 mg/kg/day and daptomycin every 48 h is insufficient to treat enterococcal bacteraemia.

Keywords

Daptomycin Bacteraemia Enterococcus faecium PK/PD modelling 

Notes

Authors’ contributions

All authors were involved in the content development of the manuscript, reviewed all drafts, and approved the final version.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Sociedade Brasileira de Microbiologia 2020

Authors and Affiliations

  • Bruna Kochhann Menezes
    • 1
  • Izabel Almeida Alves
    • 2
  • Keli Jaqueline Staudt
    • 3
  • Betina Montanari Beltrame
    • 4
  • Letícia Venz
    • 4
  • Lessandra Michelin
    • 4
  • Bibiana Verlindo Araujo
    • 5
  • Leandro Tasso
    • 1
    Email author
  1. 1.Health Sciences Graduate ProgramUniversity of Caxias do SulCaxias do SulBrazil
  2. 2.Pharmaceutical Sciences Graduate ProgramFederal University of Rio Grande do SulPorto AlegreBrazil
  3. 3.Medical Sciences Graduate ProgramFederal University of Rio Grande do SulPorto AlegreBrazil
  4. 4.College of PharmacyUniversity of Caxias do SulCaxias do SulBrazil
  5. 5.College of PharmacyFederal University of Rio Grande do SulPorto AlegreBrazil

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