Paradoxical Antibiotic Effect of Ampicillin: Use of a Population Pharmacokinetic Model to Evaluate a Clinical Correlate of the Eagle Effect in Infants With Bacteremia.
Paradoxical Antibiotic Effect of Ampicillin: Use of a Population Pharmacokinetic Model to Evaluate a Clinical Correlate of the Eagle Effect in Infants With Bacteremia.
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DOI：
10.1097/inf.0000000000002663
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发表时间：
2020-08
期刊：
影响因子：
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通讯作者：
Best Pharmaceuticals for Children Act – Pediatric Trials Network
中科院分区：
文献类型：
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作者：
Ericson JE;Hornik CP;Greenberg RG;Clark RH;Tremoulet AH;Le J;Cohen-Wolkowiez M;Smith PB;Benjamin DK Jr;Best Pharmaceuticals for Children Act – Pediatric Trials Network
背景：高剂量的氨苄青霉素常用于婴儿以达到治疗药物浓度。一种矛盾的抗生素效应，通常被称为鹰效应，当抗生素浓度增加到阈值以上时会导致疗效降低。目前尚不清楚氨苄青霉素治疗的婴儿是否有这种矛盾效应的风险。方法：我们确定了1997年至2012年年龄< 28天的大肠杆菌，肠球菌或无乳链球菌（B组链球菌）血流感染的婴儿，并在之前纳入氨苄青霉素药代动力学（PK）建模研究。我们使用单独的逻辑回归模型比较了氨苄青霉素剂量、高于最小抑制浓度的估计时间（T> MIC）和PK参数的死亡几率。调整后的逻辑回归和泊松模型分别用于计算延长菌血症≥ 3天的几率和菌血症的持续时间，剂量，T> MIC和多个PK parameters.Results：在1272名符合纳入标准的婴儿中，血培养阳性后7或30天的死亡几率与任何给药方案或PK参数评估的矛盾效应不一致。在最低剂量类别和最低日剂量类别中，菌血症延长的几率最低，但与0 - 24小时的浓度时间曲线下面积或稳态时的最大或最小浓度无关。T> MIC ≥ 50%的给药间隔与减少菌血症的持续时间和延长bacteremia.Conclusions的几率相关：这是不可能的，矛盾的抗生素作用将有临床相关性时，氨苄青霉素用于新生儿菌血症。T> MIC≥ 50%可降低菌血症持续时间和延长菌血症的几率。
Background:High doses of ampicillin are often used to achieve therapeutic drug concentrations in infants. A paradoxical antibiotic effect, often called the Eagle effect, occurs when increasing concentrations of antibiotic above a threshold results in decreased efficacy. It is unknown if infants treated with ampicillin are at risk for this paradoxical effect.Methods:We identified infants< 28 days of age with Escherichia coli, Enterococcus or Streptococcus agalactiae (group B streptococcus) bloodstream infections from 1997 to 2012 and previously included in an ampicillin pharmacokinetic (PK) modeling study. We compared the odds of death for ampicillin dose, estimated time above the minimum inhibitory concentration (T> MIC) and PK parameters using separate logistic regression models. Adjusted logistic regression and Poisson models were used to calculate the odds of prolonged bacteremia≥ 3 days and the duration of bacteremia, respectively, for dose, T> MIC and multiple PK parameters.Results:Among 1272 infants meeting inclusion criteria, odds of death 7 or 30 days after the positive blood culture were not consistent with a paradoxical effect across any of the dosing regimens or PK parameters evaluated. The odds of prolonged bacteremia was lowest at the lowest dose category and the lowest daily dose category but not associated with the area-under-the-concentration time curve from 0 to 24 hours, or the maximum or minimum concentrations at steady state. T> MIC of≥ 50% of the dosing interval was associated with decreased duration of bacteremia and odds of prolonged bacteremia.Conclusions:It is unlikely that a paradoxical antibiotic effect will have a clinical correlate when ampicillin is used for neonatal bacteremia. A T> MIC≥ 50% decreased both duration of bacteremia and odds of prolonged bacteremia.