Intestinal fatty-acid binding protein and metronidazole response in premature infants.

Fatty acid-binding proteins are small (14-15 kD) proteins that transport fatty acids in enterocytes. Human intestinal fatty acid-binding protein (I-FABP) is found in mature enterocytes of the small intestine [1]. This protein is rapidly released in blood in response to intestinal mucosal injury [2]. Studies in mature enterocytes vs. fetal intestinal cell lines, and in human organ cultures from older children vs. fetuses, suggest that immature enterocytes respond to inflammatory stimulation with excessive pro-inflammatory cytokine production [3]. This inflammatory response may be associated with the development of necrotizing enterocolitis, a disease that results in intestinal necrosis in premature infants. In this population, urinary I-FABP (I-FABPu) has been investigated as a biomarker for early diagnosis and disease severity [4–7]. As I-FABP can be easily measured in urine, it is a suitable biomarker for evaluation in premature infants because blood volume is a limiting factor for laboratory monitoring in this population. There are very limited data on the abundance of I-FABP as a function of early development. One study used human gut specimens from aborted fetuses ranging from 13–20 weeks gestation, jejunal biopsies from a 2-year-old child, and jejunal and colonic samples from adults. I-FABP expression was detected throughout the intestine in the fetal samples. Also, I-FABP expression was similar in the 15-week fetus, 2-year-old, and adults, but lower in the 20-week fetus [8]. Treatment of complicated intra-abdominal infections (e.g., necrotizing enterocolitis [NEC]) in premature infants is empirical and based on clinical signs/symptoms and radiographic findings. Metronidazole, an antibiotic with a broad anaerobic spectrum and excellent tissue penetration, is often included in treatment regimens for these infections. While empiric use of metronidazole in NEC is common, its efficacy is not adequately supported [9]. As I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy, we explored the association between metronidazole exposure and I-FABPu concentrations in critically ill premature infants.