Objectives

Different methods are used to determine the minimum inhibitory concentration (MIC) for daptomycin. The threshold is unknown for the free drug area under the concentration–time curve to MIC ratio (fAUC/MIC) of daptomycin using broth microdilution (BMD) to predict outcome of vancomycin-resistant enterococcus (VRE) bacteremia. The MIC testing method which is best for predicting the outcome remains unclear.

Methods

This is a retrospective cohort study. The inclusion criterion was VRE bacteremia treated with ≥ 8 mg/kg of daptomycin. As we aimed to compare different daptomycin MIC testing methods for predicting the clinical outcome of VRE bacteremia, the inclusion criteria included the availability of MIC values for BMD, Etest, and automated antimicrobial susceptibility testing (AST). The primary end point was 28-day mortality. The fAUC/MIC was dichotomized using classification and regression tree analysis for predicting survival.

Results

A total of 393 patients were included; 215 survived and 178 died. In the multivariable logistic model for predicting mortality, the dichotomized fAUC/MICs for Etest and AST were 0.508 and 0.065 times as probable, respectively, as that for BMD to minimize information loss. An fAUC/MIC > 75.07 for BMD significantly predicted lower mortality (adjusted odds ratio, 0.53, 95% confidence interval, 0.30–0.95; P = 0.03) after adjusting for underlying disease and bacteremia severity. Using Monte Carlo simulation, none of the doses had a probability of target attainment of ≥ 50% with an MIC of ≥ 2 mg/L.

Conclusion

The dichotomized threshold for fAUC/MIC for BMD was the best predictor of mortality. An fAUC/MIC > 75.07 for BMD independently predicted better survival.

中文翻译：

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肉汤微量稀释法预测耐万古霉素肠球菌血流感染结果的达托霉素曲线下面积与最小抑菌浓度比

目标

使用不同的方法来确定达托霉素的最低抑菌浓度 (MIC)。使用肉汤微量稀释 (BMD) 预测耐万古霉素肠球菌 (VRE) 菌血症结果的达托霉素浓度-时间曲线下游离药物面积与 MIC 比 ( f AUC/MIC) 的阈值未知。最适合预测结果的 MIC 测试方法仍不清楚。

方法

这是一项回顾性队列研究。纳入标准是用≥ 8 mg/kg 的达托霉素治疗的 VRE 菌血症。由于我们旨在比较不同的达托霉素 MIC 测试方法来预测 VRE 菌血症的临床结果，因此纳入标准包括 BMD、Etest 和自动抗菌药敏试验 (AST) 的 MIC 值的可用性。主要终点是 28 天死亡率。使用分类和回归树分析对f AUC/MIC 进行二分法，以预测存活率。

结果

共纳入 393 名患者；215 人幸存，178 人死亡。在预测死亡率的多变量逻辑模型中，Etest 和 AST 的二分法f AUC/MIC 分别是 BMD 的 0.508 和 0.065 倍，以最大限度地减少信息丢失。 在调整基础疾病和菌血症严重程度后，BMD的f AUC/MIC > 75.07 显着预测死亡率降低（调整优势比，0.53, 95% 置信区间，0.30-0.95；P = 0.03）。使用 Monte Carlo 模拟，没有一个剂量具有 ≥ 50% 的目标达到概率和 ≥ 2 mg/L 的 MIC。

结论

BMD 的f AUC/MIC的二分阈值是死亡率的最佳预测指标。BMD的f AUC/MIC > 75.07 独立预测更好的生存率。