ANTIMICROBIAL PHARMACOKINETICS IN HIGH RISK INFANTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项多中心、前瞻性、开放标签的常用抗菌药的药代动力学研究。住院的男性和女性足月儿和早产儿怀孕32周，出生后年龄不超过120日，并且接受主要研究方案(即PPRU#10824)中正在研究的抗菌剂之一的可能性很高，将有资格参加。 该议定书的目的是为持续收集新生儿的血液和尿液样本提供一种机制。这些样本将被用来测量新生儿人群中使用的抗微生物产品的水平，因为早产儿或足月儿的药代动力学数据有限。我们将获得托儿所常用抗菌产品的新生儿药代动力学数据，以便为新生儿使用它们提供更合理的方法，并允许收集有限的必要数据，用于(美国国立卫生研究院和工业)资助的外部试验。 所有婴儿将通过父母知情同意+HIPAA进行登记。家长将有足够的时间提问并签署同意文件。人口统计数据，包括性别、种族、种族、胎龄、出生体重、APGAR评分、出生后年龄和当前体重将在进入研究时被记录下来。对于出生后7天及以下的婴儿，还将收集以下信息：母体肌酐(如果有)和潜在肾毒素的母体治疗。还将在登记时和整个研究期间收集有关伴随疾病状态/医疗条件和药物的以下信息：需要血管升压剂支持以维持血压、是否存在先天性泌尿生殖道畸形、当前或以前使用肾毒性药物治疗、当前或以前使用其他抗菌药物和/或抗真菌药物治疗。根据lNICU的标准方案，将按标准重量剂量进行抗菌/抗真菌治疗。血清抗菌/抗真菌水平也将根据临床护理标准进行测量。在第一次服用抗菌药物/抗真菌药物之前，将监测肾功能，然后在接受抗菌药物/抗真菌治疗期间不超过每天。3-5份血样将在2周内采集，受试者参与本次研究。每个血样约为100-300微升。这些样本将提供有关正确的抗菌剂时间和剂量的具体信息。作为标准败血症/脑膜炎检查的一部分，在开始抗微生物和/或抗真菌治疗之前收集的尿液结果将从临床实验室获得(如果有)。或者，在注射第一剂抗微生物药物或抗真菌药物之后，最好在注射第二剂抗菌药物或抗真菌药物之前，通过尿管(如果有)或会阴处使用粘性尿液收集袋收集尿样。在所有受试者中，在婴儿接受抗菌/抗真菌治疗期间，还将每天收集用于蛋白质组分析的尿液。如果不能每天采集尿样，应在以下时间点(如果适用)采集尿样：治疗第1、3、7、14天和治疗后第1天。如果可能，也强烈鼓励在治疗第5天和第10天采集样本。尿液将通过尿管(如果有)或尿液收集袋收集大约12小时。如果使用导尿管，Foley袋将根据机构方案被排空，在12小时内收集的所有尿液将被汇集。如果使用收集袋，收集袋将在每个空隙后清空，并在12小时内汇集样本。在12小时的收集间隔内，从Foley或粘合剂收集袋中收集的所有汇集的尿液应保持在4℃。为了获得足够的容量用于后续的蛋白质组分析，强烈建议收集尿液至少12小时。如果这是不可能的，一个现场尿样至少5毫升将是可以接受的。所有现场尿样应在早上(即1000岁之前)采集，以控制尿蛋白表达的潜在每日变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Multi-center, prospective, open label pharmacokinetic study of commonly used antimicrobial agents. Hospitalized male and female term and preterm infants 32 weeks gestation with a postnatal age of 120 days or less and a high probability of receiving one of the antimicrobial agents being studied in the primary study protocol (i.e., PPRU #10824) will be eligible for enrollment. The purpose of this protocol is to provide a mechanism for the ongoing collection of blood and urine samples in neonates. These samples will be used to measure levels of antimicrobial products used in the neonatal population where there are limited pharmacokinetic data in either premature or term infants. We will obtain neonatal pharmacokinetic data for commonly used antimicrobial products in the nursery to provide a more rational approach to their use in newborn infants and to permit the collection of limited requisite data for extramurally (NIH and industry) funded trials. All infants will be enrolled via informed parental consent + HIPAA. Parents will be given enough time to ask questions and sign the consent documents. Demographic data including sex, ethnicity, race, gestational age, birth weight, APGAR scores, postnatal age and current weight will be recorded upon entry into the study. In infants postnatal ages 7 days and less the following information will also be collected: maternal creatinine (if available) and maternal treatment with potential nephrotoxins. The following information regarding concomitant disease states / medical conditions and medications will also be collected at enrollment and throughout the duration of the study period: need for vasopressor support to maintain blood pressure, presence /absence of congenital malformations of the genitourinary tract, current or prior treatment with nephrotoxic agents, current or prior treatment with other antimicrobial and/or antifungal agents. Antimicrobial/antifungal therapy will be administered at standard weight-based doses as per the lNICU's standard protocol. Serum antimicrobial/antifungal levels will be also be measured per the clinical standard of care. Renal function will be monitored before the first antimicrobial / antifungal dose and then no more than daily while receiving antimicrobial/ antifungal treatment. 3 -5 samples of blood will be collected over a 2 week is the subject participates in this study. Each blood sample will be about 100-300 micro liter. The samples will provide specific information about correct timing and dosing of antimicrobials. Results of urine collected prior to initiation of antimicrobial and/or antifungal therapy as part of the standard sepsis/meningitis work-up will be obtained from the clinical laboratory, if available. Alternately, a urine sample will be collected following administration of the first anti-microbial or antifungal dose and preferably before administration of the second antimicrobial or antifungal dose via a urinary catheter (if present) or an adhesive urine collection bag applied to the perineum. In all subjects, urine for proteomic analysis will also be collected daily while the infant is receiving antimicrobial/antifungal treatment. If daily collection is not feasible, urine samples should be collected at the following time points (if applicable): treatment days 1, 3, 7, 14 & post-treatment day 1. Collection of samples on treatment days 5 and 10 are also strongly encouraged if possible. Urine will be collected for approximately 12 hours via a urinary catheter (if present) or a urine collection bag. If a catheter is used, the Foley bag will be emptied according to institutional protocol and all urine colleted over a 12 hour period will be pooled. If a collection bag is used, it will be emptied after each void and samples pooled over the 12-hour period. During the 12-hour collection interval, all pooled urine collected from the Foley or adhesive collection bag should be maintained at 4¿C. In order to obtain a sufficient volume for subsequent proteomic analysis, it is strongly encouraged that urine be collected for at least 12 hours. If this is not possible, a single spot urine sample of at least 5mL will be acceptable. All spot urine samples should be collected in the morning (i.e., prior to 1000) to control for potential diurnal variations in urinary protein expression.