Pharmacokinetic/pharmacodynamic parameters of teicoplanin for predicting clinical outcome of glycopeptide-susceptible Enterococcus faecium bacteraemia.
{"title":"Pharmacokinetic/pharmacodynamic parameters of teicoplanin for predicting clinical outcome of glycopeptide-susceptible <i>Enterococcus faecium</i> bacteraemia.","authors":"Ryo Yamaguchi, Takehito Yamamoto, Sohei Harada, Mayu Shibuya, Miyuki Mizoguchi, Yoshimi Higurashi, Miho Echizenya, Takeya Tsutsumi, Tappei Takada","doi":"10.1093/jacamr/dlaf151","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study was to determine the pharmacokinetic/pharmacodynamic parameters of teicoplanin associated with optimal outcomes in glycopeptide-susceptible <i>Enterococcus faecium</i> (GSEF) bacteraemia.</p><p><strong>Patients and methods: </strong>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<sub>24</sub>) was calculated using a Bayesian approach. The free AUC<sub>24</sub> (fAUC<sub>24</sub>) was estimated based on patient serum albumin levels. MICs were determined using the gradient diffusion method (Etest), and the fAUC<sub>24</sub>/MIC<sub>Etest</sub> 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<sub>24</sub>/MIC<sub>Etest</sub> value associated with treatment failure.</p><p><strong>Results: </strong>A total of 76 patients were included. Treatment failure occurred in 18 patients (23.7%). A CART-derived teicoplanin fAUC<sub>24</sub>/MIC<sub>Etest</sub> ≥ 462 was significantly associated with reduced treatment failure (<i>P</i> = 0.002). Multivariable regression analysis revealed that achievement of an fAUC<sub>24</sub>/MIC<sub>Etest</sub> ≥ 462 was an independent predictor significantly associated with reduced treatment failure (OR, 0.099; 95% CI, 0.005-0.562; <i>P</i> = 0.032).</p><p><strong>Conclusions: </strong>An fAUC<sub>24</sub>/MIC<sub>Etest</sub> ≥ 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.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf151"},"PeriodicalIF":3.3000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368495/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAC-Antimicrobial Resistance","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jacamr/dlaf151","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
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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/MICEtest 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/MICEtest 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/MICEtest ≥ 462 was significantly associated with reduced treatment failure (P = 0.002). Multivariable regression analysis revealed that achievement of an fAUC24/MICEtest ≥ 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/MICEtest ≥ 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.