Pharmacokinetic/pharmacodynamic parameters of teicoplanin for predicting clinical outcome of glycopeptide-susceptible Enterococcus faecium bacteraemia

Ryo Yamaguchi; Takehito Yamamoto; Sohei Harada; Mayu Shibuya; Miyuki Mizoguchi; Yoshimi Higurashi; Miho Echizenya; Takeya Tsutsumi; Tappei Takada

doi:10.1093/jacamr/dlaf151

Pharmacokinetic/pharmacodynamic parameters of teicoplanin for predicting clinical outcome of glycopeptide-susceptible Enterococcus faecium bacteraemia

JAC Antimicrob Resist. 2025 Aug 21;7(4):dlaf151. doi: 10.1093/jacamr/dlaf151. eCollection 2025 Aug.

Authors

Ryo Yamaguchi¹, Takehito Yamamoto¹, Sohei Harada², Mayu Shibuya³, Miyuki Mizoguchi³, Yoshimi Higurashi³, Miho Echizenya¹, Takeya Tsutsumi^{3

4}, Tappei Takada¹

Affiliations

¹ Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan.
² Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
³ Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan.
⁴ Department of Infectious Diseases, The University of Tokyo Hospital, Tokyo, Japan.

Abstract

Objectives: The objective of this study was to determine the pharmacokinetic/pharmacodynamic parameters of teicoplanin associated with optimal outcomes in glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia.

Patients and methods: We conducted a retrospective review of GSEF bacteraemia cases treated with teicoplanin between 1 April 2009 and 30 May 2023. Total area under the concentration-time curve over 24 h (AUC₂₄) was calculated using a Bayesian approach. The free AUC₂₄ (fAUC₂₄) was estimated based on patient serum albumin levels. MICs were determined using the gradient diffusion method (Etest), and the fAUC₂₄/MIC_Etest ratio was calculated. The primary outcome was treatment failure, defined as a composite of (i) 30-day all-cause mortality and (ii) microbiological failure, defined as persistent bacteraemia (a positive follow-up blood culture obtained >72 h after initiation of appropriate therapy). Classification and regression tree analysis (CART) was employed to identify the optimal teicoplanin fAUC₂₄/MIC_Etest value associated with treatment failure.

Results: A total of 76 patients were included. Treatment failure occurred in 18 patients (23.7%). A CART-derived teicoplanin fAUC₂₄/MIC_Etest ≥ 462 was significantly associated with reduced treatment failure (P = 0.002). Multivariable regression analysis revealed that achievement of an fAUC₂₄/MIC_Etest ≥ 462 was an independent predictor significantly associated with reduced treatment failure (OR, 0.099; 95% CI, 0.005-0.562; P = 0.032).

Conclusions: An fAUC₂₄/MIC_Etest ≥ 462 was associated with a reduction in treatment failure in GSEF bacteraemia. Further studies are necessary to establish optimal pharmacokinetic/pharmacodynamic targets for GSEF bacteraemia.