Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Int J Antimicrob Agents. 2019 Sep;54(3):346-350. doi: 10.1016/j.ijantimicag.2019.07.002. Epub 2019 Jul 5.
Daptomycin is commonly prescribed in combination with other antibiotics for treatment of enterococcal bacteraemia. Whilst a free drug area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) ratio >27.4 is associated with 30-day survival with daptomycin monotherapy, it is unknown whether receipt of other antibiotics affects this threshold. Data were pooled from seven published trials assessing outcomes in daptomycin-treated enterococcal bacteraemia, including patients receiving daptomycin (≥72 h) and any β-lactam, intravenous aminoglycoside, linezolid, tigecycline and/or vancomycin. Exposures were calculated using a published population pharmacokinetic model based on creatinine clearance, 90% protein binding and daptomycin Etest MIC. The fAUC/MIC threshold predictive of 30-day survival was determined by classification and regression tree analysis. Following pooling of data, 240 adults were included; 137 (57.1%) were alive at 30 days. A majority of patients were immunosuppressed (65.8%) and received a β-lactam (94.6%). Examining the threshold in low-acuity patients (n = 135) to control for co-morbidities, these patients were more likely to survive when fAUC/MIC >12.3 was achieved (63.2% vs. 20.0%; P = 0.015). The difference remained significant in a multivariable logistic regression model that controlled for infection source and immunosuppression (P = 0.017). This threshold is 2-fold lower than that observed with daptomycin monotherapy. Probabilities of threshold attainment using a 10 mg/kg/day dose were 100% for isolates with MICs ≤ 2 mg/L and 95.2% for a 12 mg/kg/day dose for MICs of 4 mg/L. These data support the use of high-dose daptomycin in combination with another antibiotic for treatment of enterococcal bacteraemia.
达托霉素常与其他抗生素联合用于治疗肠球菌菌血症。虽然达托霉素单药治疗时游离药物浓度-时间曲线下面积与最低抑菌浓度（fAUC/MIC）比值>27.4 与 30 天生存率相关，但接受其他抗生素是否会影响这一阈值尚不清楚。从评估达托霉素治疗肠球菌菌血症的七项已发表试验中汇集了数据，包括接受达托霉素（≥72 小时）和任何β-内酰胺类、静脉内氨基糖苷类、利奈唑胺、替加环素和/或万古霉素的患者。根据基于肌酐清除率、90%蛋白结合率和达托霉素 Etest MIC 的已发表群体药代动力学模型计算暴露量。通过分类回归树分析确定预测 30 天生存率的 fAUC/MIC 阈值。数据汇总后，纳入 240 例成人，30 天存活 137 例（57.1%）。大多数患者存在免疫抑制（65.8%），并接受了β-内酰胺类（94.6%）治疗。在低危患者（n=135）中检查该阈值以控制合并症，当达到 fAUC/MIC>12.3 时，这些患者更有可能存活（63.2% vs. 20.0%；P=0.015）。在控制感染源和免疫抑制的多变量逻辑回归模型中，差异仍然显著（P=0.017）。该阈值比达托霉素单药治疗时观察到的低 2 倍。对于 MIC≤2 mg/L 的分离株，10 mg/kg/天剂量达到阈值的概率为 100%，对于 MIC 为 4 mg/L 的分离株，12 mg/kg/天剂量的概率为 95.2%。这些数据支持使用高剂量达托霉素联合另一种抗生素治疗肠球菌菌血症。
