Antibiotic Safety in Infants With Complicated Intra-abdominal Infections (SCAMP Trial)

Assessing the safety, efficacy, and pharmacokinetics of a multidrug antibiotic regimen (clindamycin, ampicillin, metronidazole, and piperacillin-tazobactam) for infants with complicated intra-abdominal infections.

Summary

Complicated intra-abdominal infections are common and often fatal in premature infants. These infections often occur as a result of necrotizing enterocolitis (NEC), the pathogenesis of which involves intestinal mucosal injury, usually associated with intestinal ischemia and bacterial overgrowth. NEC has a high overall mortality (15%) and, in extremely-low-birth-weight infants (≤1000 grams), mortality for surgical NEC is nearly 50%. Survivors often suffer from complications, including stricture formation, and life-long morbidities such as short bowel syndrome. Infants who have had NEC are also at increased risk of poor neurodevelopmental outcomes.

Recommended antibiotics for complicated intra-abdominal infections in infants include combinations of ampicillin, piperacillin-tazobactam, meropenem, metronidazole, clindamycin, or gentamicin. In spite of their frequent use, however, the safety and efficacy of these antibiotics in infants with complicated intra-abdominal infections have not been established.

The PTN is seeking to fill this information gap with SCAMP, a partially-randomized, multicenter, open-label Safety study of Clindamycin, Ampicillin, Metronidazole, and Piperacillin-tazobactam in infants with complicated intra-abdominal infections. The primary objective of this study is to determine the safety of these drug regimens in this specialized context; secondary objectives include determining the drugs’ effectiveness, their pharmacokinetics in this unique population, biomarker association with disease severity and antibiotic exposure, and diversity or shift of intestinal microbiota. Approximately 284 infants, <3 months of age will be enrolled at approximately 50 sites. Total length of study participation is 100 days, including 10 days of treatment and up to 90 days of follow-up assessments.

Publications

  • Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin-Tazobactam Safety in Infants
    The Pediatric Infectious Disease Journal • September 2017 Access article on PubMed. Salerno S, Hornik CP, Cohen-Wolkowiez M, Smith PB, Ku LC, Kelly MS, Clark R, Gonzalez D; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are ...
  • Intestinal Fatty-Acid Binding Protein and Metronidazole Response in Premature Infants
    Journal of Neonatal and Perinatal Medicine • November 2014 Access article on PubMed. 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 ...

OVERVIEW

Status:
Ongoing

ClinicalTrials.gov identifier:
NCT01994993

NICHD Data and Specimen Hub (DASH): Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections - Metronidazole

Principal Investigator:
Michael Cohen-Wolkowiez, MD, PhD
Duke Health, Durham, NC

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