ANTIMICROBIAL PHARMACOKINETICS IN HIGH RISK INFANTS

Children'S Research Institute, Washington DC

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Abstract

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[unreadable]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.