ANTIMICROBIAL PHARMACOKINETICS IN HIGH RISK INFANTS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项常用抗菌药物的多中心、前瞻性、开放标签药代动力学研究。妊娠32周、出生后120天或以下且很有可能接受主要研究方案中研究的一种抗菌药物的住院男性和女性足月和早产婴儿（即，PPRU #10824）将有资格入组。 本方案的目的是提供新生儿血液和尿液样本持续采集的机制。这些样本将用于测量新生儿人群中使用的抗菌药物水平，其中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药物的新生儿药代动力学数据，以提供更合理的方法来在新生儿中使用抗菌药物，并允许收集有限的必要数据用于壁外（NIH和行业）资助的试验。 所有婴儿将通过父母知情同意+ HIPAA入组。 父母将有足够的时间提出问题并签署同意文件。 入组研究时将记录人口统计学数据，包括性别、种族、人种、胎龄、出生体重、APGAR评分、出生后年龄和当前体重。 在出生后7天及以下的婴儿中，还将收集以下信息：母体肌酐（如可用）和母体接受的潜在肾毒素治疗。还将在入组时和整个研究期间收集关于伴随疾病状态/医学状况和药物的以下信息：需要血管加压药支持以维持血压、存在/不存在先天性泌尿生殖道畸形、当前或既往接受过肾毒性药物治疗、当前或既往接受过其他抗菌剂和/或抗真菌剂治疗。 将根据INICU的标准方案以基于体重的标准剂量施用抗微生物/抗真菌疗法。还将根据临床标准治疗测量血清抗菌剂/抗真菌剂水平。在首次抗微生物/抗真菌药物给药前监测肾功能，然后在接受抗微生物/抗真菌药物治疗期间不超过每日一次。如果受试者参与本研究，将在2周内采集3 - 5份血液样本。 每份血样约为100-300微升。样本将提供有关抗菌剂正确给药时间和剂量的具体信息。 作为标准脓毒症/脑膜炎检查的一部分，开始抗菌和/或抗真菌治疗前采集的尿液结果将从临床实验室获得（如可用）。 或者，在给予第一剂抗微生物或抗真菌药物后，最好在给予第二剂抗微生物或抗真菌药物前，通过导尿管（如果存在）或应用于会阴的粘性尿液收集袋收集尿液样本。 在所有受试者中，当婴儿接受抗菌/抗真菌治疗时，还将每天采集尿液进行蛋白质组学分析。 如果每日采集不可行，则应在以下时间点（如适用）采集尿样：治疗第1、3、7、14天和治疗后第1天。如果可能，强烈建议在给药第5天和第10天采集样本。 将通过导尿管（如果有）或尿液收集袋收集尿液约12小时。 如果使用导尿管，将根据机构方案清空Foley袋，并合并12小时内收集的所有尿液。 如果使用收集袋，则在每次排空后清空收集袋，并在12小时内合并样本。 在12小时采集间隔期间，从Foley或粘性收集袋中采集的所有合并尿液应保持在4 ℃。 为了获得足够的体积用于随后的蛋白质组学分析，强烈建议收集尿液至少12小时。 如果无法做到这一点，则可接受至少5 mL的单点尿样。 所有的现场尿液样本都应该在早上收集（即，1000之前）以控制尿蛋白表达的潜在昼夜变化。

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.