Yamaguchi Ryo, Yamamoto Takehito, Harada Sohei, Shibuya Mayu, Mizoguchi Miyuki, Higurashi Yoshimi, Echizenya Miho, Tsutsumi Takeya, Takada Tappei
Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan.
Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
JAC Antimicrob Resist. 2025 Aug 21;7(4):dlaf151. doi: 10.1093/jacamr/dlaf151. eCollection 2025 Aug.
The objective of this study was to determine the pharmacokinetic/pharmacodynamic parameters of teicoplanin associated with optimal outcomes in glycopeptide-susceptible (GSEF) bacteraemia.
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 (AUC) was calculated using a Bayesian approach. The free AUC (fAUC) was estimated based on patient serum albumin levels. MICs were determined using the gradient diffusion method (Etest), and the fAUC/MIC 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 fAUC/MIC value associated with treatment failure.
A total of 76 patients were included. Treatment failure occurred in 18 patients (23.7%). A CART-derived teicoplanin fAUC/MIC ≥ 462 was significantly associated with reduced treatment failure ( = 0.002). Multivariable regression analysis revealed that achievement of an fAUC/MIC ≥ 462 was an independent predictor significantly associated with reduced treatment failure (OR, 0.099; 95% CI, 0.005-0.562; = 0.032).
An fAUC/MIC ≥ 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.
本研究的目的是确定替考拉宁在糖肽类敏感(GSEF)菌血症中取得最佳疗效相关的药代动力学/药效学参数。
我们对2009年4月1日至2023年5月30日期间接受替考拉宁治疗的GSEF菌血症病例进行了回顾性研究。采用贝叶斯方法计算24小时浓度-时间曲线下的总面积(AUC)。根据患者血清白蛋白水平估算游离AUC(fAUC)。使用梯度扩散法(Etest)测定最低抑菌浓度(MIC),并计算fAUC/MIC比值。主要结局为治疗失败,定义为以下两者的综合:(i)30天全因死亡率,以及(ii)微生物学失败,定义为持续性菌血症(在开始适当治疗>72小时后获得的随访血培养阳性)。采用分类与回归树分析(CART)来确定与治疗失败相关的最佳替考拉宁fAUC/MIC值。
共纳入76例患者。18例患者(23.7%)发生治疗失败。CART得出的替考拉宁fAUC/MIC≥462与治疗失败减少显著相关(P=0.002)。多变量回归分析显示,fAUC/MIC≥462是与治疗失败减少显著相关的独立预测因素(OR,0.099;95%CI,0.005-0.562;P=0.032)。
fAUC/MIC≥462与GSEF菌血症治疗失败减少相关。有必要进行进一步研究以确定GSEF菌血症的最佳药代动力学/药效学靶点。