Perioperative Tissue Penetration of Antimicrobials in Infants
Condition: Bowel Dysfunction
MeSH terms: Intestinal Diseases
Study type: Observational

Summary: 
      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.
      Metronidazole will be given at standard of care intravenous loading dose of 30 mg/kg 15
      minutes prior to incision, with a maximum dose of 2g. Intraoperative plasma samples will be
      obtained from pre-existing vascular access catheters at end of bolus, 30, 60, 90 minutes, at
      time of intestinal excision, and at the end of the case in ethylenediaminetetraacetic acid
      microcontainers, exceeding no more than 5mL total.
    

Detailed description: 
      This is a single center pilot pharmacokinetic (PK) study to concomitantly measure antibiotic
      concentrations in the plasma and the intestinal wall of healthy infants undergoing intestinal
      surgery.

      Metronidazole will be given at standard of care intravenous loading dose of 30 mg/kg 15
      minutes prior to incision, with a maximum dose of 2g. Exact time, dose, and infusion rate and
      duration will be recorded. The use of a loading dose will allow characterization of plasma
      and tissue PK after a single dose that would be expected with steady state dosing, thus
      increasing the translatability of the investigator's findings to cIAI treatment.

      Intraoperative plasma samples will be obtained from pre-existing vascular access catheters at
      end of bolus, 30, 60, 90 minutes, at time of intestinal excision, and at the end of the case
      in ethylenediaminetetraacetic acid microcontainers, exceeding no more than 5mL total. At the
      time of intestinal excision, the surgeon will cut at least 250mg of intestine from the
      specimen, ensuring all layers of bowel are included. This sample will be placed in a sterile,
      dry container. All samples will be processed and stored in a -80°C freezer within 1 hour of
      acquisition. Samples will be batched and shipped to a central commercial laboratory (OpAns
      Analytical Solutions LLC, Durham, NC) for concentration measurement of metronidazole and its
      primary metabolite 2-hydroxymetronidazole using a HPLC/MS/MS plasma assay previously
      developed and validated per FDA guidance. This assay will be modified and validated for
      tissue concentration measurement utilizing porcine intestinal tissue and run over three
      mediums to ensure correct measurement. The samples will also be used to quantify CYP2A6
      protein levels using commercially available enzyme-linked immunosorbent assay kits.
    

Intervention name(s): Bowel Surgery with Metronidazole
Intervention type(s): Procedure
Intervention description(s): Metronidazole will be given per standard of care prior to incision. Intraoperative plasma samples will be obtained from pre-existing vascular access catheters at end of bolus, 30, 60, 90 minutes, at time of intestinal excision(s), and at the end of the case in ethylenediaminetetraacetic acid microcontainers, exceeding no more than approximately 5 mL total.
At the time of intestinal excision, the surgeon will cut at least 500 mg of intestine from the specimen, ensuring all layers of bowel are included. If more than one intestinal sample is taken during the surgery, such as in the case of multiple strictures removed, each sample will be obtained and labeled appropriately.
Intervention MeSH terms: Metronidazole
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Children < 2 years of age undergoing intestinal surgery
      
Biospecimen description: 
      Plasma samples Intestinal tissue