M R Sampson1, B T Bloom2, A Arrieta3, E Capparelli4, D K Benjamin5, P B Smith5, G L Kearns6, J van den Anker7, M Cohen-Wolkowiez5. 1. Duke Clinical Research Institute, Durham, NC, USA UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. 2. Wichita Medical Research and Education Foundation, Wichita, KS, USA. 3. Children's Hospital-Orange County, Orange, CA, USA. 4. Schools of Medicine and Pharmacy, University of California-San Diego, La Jolla, CA, USA. 5. Duke Clinical Research Institute, Durham, NC, USA Department of Pediatrics, Duke University, Durham, NC, USA. 6. Division of Pediatric Pharmacology and Therapeutic Innovation, Children's Mercy Hospital, Kansas City, MO, USA Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. 7. Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA.
Abstract
OBJECTIVES: 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 released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. STUDY DESIGN: We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. RESULTS: Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p = 0.006). CONCLUSION: While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants.
OBJECTIVES: 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 released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. STUDY DESIGN: We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. RESULTS: Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p = 0.006). CONCLUSION: While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants.
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Authors: Michael Cohen-Wolkowiez; Mario Sampson; Barry T Bloom; Antonio Arrieta; James L Wynn; Karen Martz; Barrie Harper; Gregory L Kearns; Edmund V Capparelli; David Siegel; Daniel K Benjamin; P Brian Smith Journal: Pediatr Infect Dis J Date: 2013-09 Impact factor: 2.129
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