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Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets

机译:儿童假单胞菌感染美罗培南的剂量方案未达到血清浓度目标

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摘要

There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high‐risk children and adults. We evaluated this observation in children using literature studies conducted in infants and children. Observed and, as necessary, simulated data from the literature were combined, yielding a data set of 288 subjects (1 day to ~ 17 years). A population pharmacokinetic model was fit to the data and then used to simulate the recommended dosing regimens and estimate the proportion of subjects achieving recommended target exposures. A two‐compartment model best fit the data with weight, postnatal age, gestational age, and serum creatinine as covariates. The US Food and Drug Administration (FDA)‐approved dosing regimens achieved targets in ~ 90% or more of subjects less than 3 months of age for organisms with minimum inhibitory concentration (MIC)'s of 2 and 4 mg/L; however, only 68.4% and 41.7% of subjects older than 3 months and weighing 3 months" corrected to "less than 3 months".]. Moreover, for subjects weighing more than 50 kg, only 41.3% and 17% achieved these respective targets. Simulation studies were used to explore the impact of changing dose, dosing interval, and infusion duration on the likelihood of achieving therapeutic targets in these groups. Our findings illustrate that current dosing recommendations for children over 3 months of age fail to meet therapeutic targets in an unacceptable fraction of patients. Further investigation is needed to develop new dosing strategies in these patients.
机译:有文献报道,在一些高危儿童和成人中,一些推荐的美罗培南剂量方案可能无法达到治疗目标。我们使用对婴儿和儿童进行的文献研究,对儿童的这一观察结果进行了评估。结合文献中观察到的和必要时的模拟数据,得出288个受试者的数据集(1天至17年)。将群体药代动力学模型拟合到数据,然后用于模拟推荐的给药方案并估算达到推荐目标暴露的受试者比例。两室模型最适合以体重,出生年龄,胎龄和血清肌酐为协变量的数据。美国食品药品监督管理局(FDA)批准的给药方案在3个月以内的最低抑菌浓度(MIC)为2和4 mg / L的生物体中,约90%或更多的受试者达到了目标;但是,年龄在3个月以上且体重在3个月以上的受试者中,只有68.4%和41.7%被纠正为“少于3个月”。]此外,体重超过50公斤的受试者中,只有41.3%和17%达到了上述目标通过模拟研究探讨了改变剂量,给药间隔和输注持续时间对这些人群达到治疗目标的可能性的影响,我们的发现表明,目前针对3个月以上儿童的给药建议未能达到治疗目标。需要接受进一步的研究以开发针对这些患者的新剂量策略。

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