Ruiz Jesus, Ramirez Paula, Villarreal Esther, Gordon Mónica, Sánchez María Ángeles, Martín María, Castellanos-Ortega Álvaro
Intensive Care Unit, IIS La Fe, Hospital Universitario y Politecnico de La Fe, Valencia, Spain.
Intensive Care Unit, Hospital Universitario y Politecnico de La Fe, Valencia, Spain.
SAGE Open Med. 2020 Sep 18;8:2050312120958897. doi: 10.1177/2050312120958897. eCollection 2020.
The information about the pharmacokinetics and optimal dose of tigecycline in critically ill patients with severe underlying diseases is limited and controversial. In this study, we evaluate the pharmacokinetic parameters of tigecycline in critically ill patients with multidrug-resistant Gram-negative infection and explore the association between the pharmacokinetic/pharmacodynamic ratio and treatment response.
A prospective study was designed including critically ill patients treated with tigecycline for multidrug-resistant Gram-negative infections. Blood samples were collected at day 3-5 of treatment, and pharmacokinetics parameters were evaluated using NONMEM software. Relationship between area under the free concentration-time curve and minimum inhibitory concentration ratio (fAUC/MIC) and treatment failure was evaluated. Association between tigecycline fAUC and hepatobiliary toxicity was also investigated.
Twenty-five critically ill patients were included in the study. In the pharmacokinetic model, weight and total bilirubin level were found to be significant predictors of tigecycline clearance. Fifteen (60.0%) patients achieved an fAUC/MIC ratio >4.5, seven (28.0%) an fAUC/MIC > 6.96 and only three (12.0%) an fAUC/MIC > 17.9. No differences in fAUC/MIC ratio were obtained between those patients with and without clinical failure (5.28 (IC95%: 2.57-7.94) vs 8.71 (3.57-13.84)). fAUC values were higher in those patients who suffered hepatobiliary disorders (7.63 (3.93-11.34) vs 17.63 (7.85-26.28) mg/L/h).
An important percentage of critically ill patients with multidrug-resistant Gram-negative infection treated with tigecycline do not achieve an appropriate pharmacokinetic/pharmacodynamic value. Tigecycline fAUC seems to be associated with hepatobiliary disorders in this study population. The effect of fAUC/MIC ratio on clinical response remains unclear.
关于替加环素在患有严重基础疾病的重症患者中的药代动力学和最佳剂量的信息有限且存在争议。在本研究中，我们评估了替加环素在患有多重耐药革兰阴性菌感染的重症患者中的药代动力学参数，并探讨了药代动力学/药效学比值与治疗反应之间的关联。
设计了一项前瞻性研究，纳入接受替加环素治疗多重耐药革兰阴性菌感染的重症患者。在治疗的第3至5天采集血样，并使用NONMEM软件评估药代动力学参数。评估游离浓度-时间曲线下面积与最低抑菌浓度比值（fAUC/MIC）与治疗失败之间的关系。还研究了替加环素fAUC与肝胆毒性之间的关联。
本研究纳入了25例重症患者。在药代动力学模型中，体重和总胆红素水平被发现是替加环素清除率的重要预测因素。15例（60.0%）患者的fAUC/MIC比值>4.5，7例（28.0%）患者的fAUC/MIC>6.96，只有3例（12.0%）患者的fAUC/MIC>17.9。有临床失败和无临床失败的患者之间的fAUC/MIC比值没有差异（5.28（IC95%：2.57 - 7.94）对8.71（3.57 - 13.84））。患有肝胆疾病的患者的fAUC值更高（7.63（3.93 - 11.34）对17.63（7.85 - 26.28）mg/L/h）。
接受替加环素治疗的患有多重耐药革兰阴性菌感染的重症患者中有相当比例未达到合适的药代动力学/药效学值。在本研究人群中，替加环素fAUC似乎与肝胆疾病有关。fAUC/MIC比值对临床反应的影响仍不清楚。
