Artificial Intelligence and Amikacin Exposures Predictive of Outcomes in Multidrug-Resistant Tuberculosis Patients.
Artificial Intelligence and Amikacin Exposures Predictive of Outcomes in Multidrug-Resistant Tuberculosis Patients.
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DOI：
10.1128/aac.00962-16
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发表时间：
2016-10
影响因子：
4.9
通讯作者：
Gumbo T
中科院分区：
文献类型：
--
作者：
Modongo C;Pasipanodya JG;Magazi BT;Srivastava S;Zetola NM;Williams SM;Sirugo G;Gumbo T
氨基糖苷类药物如阿米卡星仍然是治疗耐多药结核病（MDR-TB）的主要药物。我们测量了博茨瓦纳28例接受阿米卡星联合口服左氧氟沙星、乙硫异烟胺、环丝氨酸和吡嗪酰胺治疗的MDR-TB患者的阿米卡星浓度，并计算了0至24 h的浓度-时间曲线下面积（AUC 0 -24）。根据液体培养，每月随访患者痰培养转化情况。阿米卡星治疗的中位持续时间为184（范围：28 - 866）天，中位剂量为17.30（范围：11.11 - 19.23）mg/kg。只有11例（39%）患者在治疗期间痰培养转化;其余患者失败。我们利用分类和回归树分析（CART）来检查所有潜在的失败预测因素，包括临床和人口统计学特征、合并症和阿米卡星峰浓度（Cmax）、AUC 0 -24和谷浓度。失败的主要节点有两个竞争变量，Cmax <67 mg/L和AUC 0 -24 <568.30 mg · h/L;体重>41 kg是次要节点，相对于主要节点得分为35%。CART模型的受试者工作特征曲线下面积在后测时为R2 = 0.90。在体重>41 kg的患者中，阿米卡星Cmax ≥67 mg/L的患者痰菌转化率为3/3（100%），而Cmax <67 mg/L的患者为3/15（20%）（相对风险[RR] = 5.00; 95%置信区间[CI]，1.82 - 13.76）。在所有阿米卡星Cmax和AUC 0 -24均低于阈值的患者中，7/7（100%）失败，而这些参数高于阈值的患者中有7/15（47%）失败（RR = 2.14; 95% CI，1.25 - 43.68）。这些阿米卡星剂量-时间表模式和暴露量与中空纤维系统模型中确定的模式和暴露量几乎相同。
Aminoglycosides such as amikacin continue to be part of the backbone of treatment of multidrug-resistant tuberculosis (MDR-TB). We measured amikacin concentrations in 28 MDR-TB patients in Botswana receiving amikacin therapy together with oral levofloxacin, ethionamide, cycloserine, and pyrazinamide and calculated areas under the concentration-time curves from 0 to 24 h (AUC0–24). The patients were followed monthly for sputum culture conversion based on liquid cultures. The median duration of amikacin therapy was 184 (range, 28 to 866) days, at a median dose of 17.30 (range 11.11 to 19.23) mg/kg. Only 11 (39%) patients had sputum culture conversion during treatment; the rest failed. We utilized classification and regression tree analyses (CART) to examine all potential predictors of failure, including clinical and demographic features, comorbidities, and amikacin peak concentrations (Cmax), AUC0–24, and trough concentrations. The primary node for failure had two competing variables, Cmax of <67 mg/liter and AUC0–24 of <568.30 mg · h/L; weight of >41 kg was a secondary node with a score of 35% relative to the primary node. The area under the receiver operating characteristic curve for the CART model was an R2 = 0.90 on posttest. In patients weighing >41 kg, sputum conversion was 3/3 (100%) in those with an amikacin Cmax of ≥67 mg/liter versus 3/15 (20%) in those with a Cmax of <67 mg/liter (relative risk [RR] = 5.00; 95% confidence interval [CI], 1.82 to 13.76). In all patients who had both amikacin Cmax and AUC0–24 below the threshold, 7/7 (100%) failed, compared to 7/15 (47%) of those who had these parameters above threshold (RR = 2.14; 95% CI, 1.25 to 43.68). These amikacin dose-schedule patterns and exposures are virtually the same as those identified in the hollow-fiber system model.