This study evaluated the safety and pharmacokinetics (PK) of intravenous metronidazole in premature infants with suspected serious infection. Twenty-four participants, less than 32 weeks gestational age with suspected serious infection, participated in the study for up to 15 days at three centers. The Pediatric Trials Network generated PK data to guide dosing of metronidazole in premature infants using a simplified dosing regimen based on postmenstrual age.
Gregory Kearns, PharmD, PhD, of Children's Mercy Hospital Kansas City, discusses the PTN metronidazole study: clinical pharmacology in action.
Brian Smith, MD, MPH, of the Duke Clinical Research Institute, discusses the metronidazole in premature infants study.
Metronidazole is approved by the U.S. Food and Drug Administration for the treatment of adults with infections caused by anaerobic bacteria. Children and premature infants may be affected by these bacteria too; therefore, doctors frequently give metronidazole to infants who are suspected of having an infection caused by anaerobic bacteria. However, the appropriate dose of metronidazole in premature infants is not well-known.
We enrolled 24 babies <32 weeks gestational age with suspected serious infection and administered metronidazole for up to five days, measuring the levels of metronidazole in each baby. With this information, we were able to determine the appropriate dose of metronidazole in premature infants. Because metronidazole likely behaves differently in premature infants than it does in term infants, older children, and adults, this study meets a public health need for better evidence in the treatment of this vulnerable group.
- Metronidazole Metabolism in Neonates and the Interplay Between Ontogeny and Genetic Variation The Journal of Clinical Pharmacology • February 2017. Wang LA, Gonzalez D, Leeder JS, Tyndale RF, Pearce RE, Benjamin DK Jr, Kearns GL, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Metronidazole is commonly used to treat intra-abdominal infections in neonates. The parent drug is converted to 5 metabolites, with 2-hydroxy-metronidazole being the most ...
- Intestinal Fatty-Acid Binding Protein and Metronidazole Response in Premature Infants Journal of Neonatal and Perinatal Medicine • November 2014. Sampson MR, Bloom BT, Arrieta A, Capparelli E, Benjamin DK Jr, Smith PB, Kearns GL, van den Anker J, Cohen-Wolkowiez M. In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is ...
- Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants The Pediatric Infectious Disease Journal • July 2013. Cohen-Wolkowiez M, Sampson M, Bloom BT, Arrieta A, Wynn JL, Martz K, Harper B, Kearns GL, Capparelli EV, Siegel D, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network. Limited pharmacokinetic (PK) data of metronidazole in premature infants have led to various dosing recommendations. Surrogate efficacy targets ...
Published; clinical study report submitted to FDA
Michael Cohen-Wolkowiez, MD, PhD and Daniel K. Benjamin, MD, PhD, MPH
Duke Health, Durham, NC
- DCRI researchers complete first drug study for Pediatric Trials Network DCRI investigators have completed the study of metronidazole, an anti-microbial agent frequently administered to infants suffering from necrotizing enterocolitis. The Duke Clinical Research Institute has completed its first drug trial conducted for the Pediatric Trials Network (PTN). Late last year (2011), DCRI investigators completed their study of metronidazole, an anti-microbial agent frequently administered to infants suffering from ...