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

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 offC_max/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 fC_max/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 thatfC_max/MIC and fAUC₂₄/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.

Keywords: Methicillin-resistant Staphylococcus aureus; Methicillin-susceptible Staphylococcus aureus; Neutropenic murine thigh infection model; Pharmacokinetics/pharmacodynamics; Teicoplanin.