Perioperative Tissue Penetration of Antimicrobials in Infants
BACKGROUND: Antibiotic concentrations in the intestines depend upon uptake from the blood stream into the intestinal wall and local metabolism, both of which are complex and understudied processes involving intestinal perfusion, endothelial integrity, and expression and function of metabolizing enzymes and transporters. Both processes are affected by pathophysiologic alterations of complicated intra-abdominal infections (cIAI) and by infant growth and maturation and remain incompletely understood. GAP: This study aims to define the pharmacokinetic (PK) properties of a commonly used antibiotic to treat cIAI, metronidazole, in the intestinal wall tissue of healthy infants undergoing intestinal surgery to optimize intestinal wall penetration of antibiotics in infants. HYPOTHESIS: Intestinal wall penetration and metabolism of metronidazole in infants will vary with age and require optimization of current dosing regimens to achieve adequate target tissue penetration. METHODS: This study is an open-label pilot PK study to concomitantly measure antibiotic concentrations in the plasma and the intestinal wall of infants without cIAI undergoing intestinal operations. RESULTS: Pending. IMPACT: Intestinal antibiotic concentrations in infants are unknown, which poses significant risk of under treatment with cIAI, where mortality can approach 30%. This pilot study will collect essential tissue penetration data of metronidazole in healthy infantile intestines to inform the design of future studies in a cIAI population and help establish an efficient platform to broadly study tissue distribution of medications in infants by leveraging intraoperative biospecimen collection and PK modeling.