Pharmacokinetic/pharmacodynamic evaluation of teicoplanin against Staphylococcus aureus in a murine thigh infection model

Erika Watanabe, Kazuaki Matsumoto, Kazuro Ikawa, Yuta Yokoyama, Akari Shigemi, Yuki Enoki, Yasuhiro Umezaki, Koyo Nakamura, Keiichiro Ueno, Hideyuki Terazono, Norifumi Morikawa, Yasuo Takeda

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Pharmacokinetic/pharmacodynamic (PK/PD) analysis using murine infection models is a well-established methodology for optimising antimicrobial therapy. Therefore, we investigated the PK/PD indices of teicoplanin againstStaphylococcus aureus using a murine thigh infection model. Methods: Mice were rendered neutropenic by administration of a two-step dosing of cyclophosphamide. Then, isolates of methicillin-susceptibleS. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) were inoculated into the thighs of neutropenic mice. PK/PD analyses were performed by non-linear least-squared regression using the MULTI program. Results: Target values offCmax/MIC (r2 = 0.94) of teicoplanin for static effect and 1 log10 kill against MSSA were 4.44 and 15.44, respectively. Target values of fAUC24/MIC (r2 = 0.92) of teicoplanin for static effect and 1 log10 kill against MSSA were 30.4 and 70.56, respectively. Target values of fCmax/MIC (r2 = 0.91) of teicoplanin for static effect and 1 log10 kill against MRSA were 8.92 and 14.16, respectively. Target values of fAUC24/MIC (r2 = 0.92) of teicoplanin for static effect and 1 log10 kill against MRSA were 54.8 and 76.4, respectively. Conclusion: These results suggest thatfCmax/MIC and fAUC24/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.

Original languageEnglish
Pages (from-to)83-87
Number of pages5
JournalJournal of Global Antimicrobial Resistance
Volume24
DOIs
Publication statusPublished - 2021 Mar
Externally publishedYes

Keywords

  • Methicillin-resistant Staphylococcus aureus
  • Methicillin-susceptible Staphylococcus aureus
  • Neutropenic murine thigh infection model
  • Pharmacokinetics/pharmacodynamics
  • Teicoplanin

ASJC Scopus subject areas

  • Microbiology
  • Immunology and Allergy
  • Immunology
  • Microbiology (medical)

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