Nosocomial sepsis is associated with increased mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay. Prevention of sepsis especially in the preterm infants in the neonatal intensive care unit remains a major challenge. The gastrointestinal tract is an important source of potential pathogens causing nosocomial sepsis as the immature intestinal epithelium can permit translocation of bacteria and yeast. The intestinal tract and its microflora play an important role in the immunity. Altering the gut microflora has been extensively studied for immunomodulation in preterm infants. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Probiotics have been used for prevention and treatment of various medical conditions in children and adults. Studies on probiotics in premature infants have focused on normalizing intestinal flora, improvement in feeding intolerance, prevention of necrotizing enterocolitis and sepsis. In this paper, we discuss the intestinal bacterial colonization pattern; the rational for probiotics and prebiotic therapy with special focus on the prevention of nosocomial sepsis in preterm infants. 1. Introduction Nosocomial infection (also referred to as late onset neonatal sepsis (LOS) or health care associated infection) in the neonatal intensive care units (NICU) is associated with morbidity and mortality, prolonged hospitalization, and increased medical costs [1]. Neonates, especially premature infants, are at high risk of acquiring nosocomial infections because of impaired host-defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at the time of birth, reduced barrier function of their skin, use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotic agents [1]. The nosocomial infection rate in the NICUs has increased over the past decades. About 6.2 to 33% of all neonates admitted to the NICU developed nosocomial infection [2]. Of all the very low birth weights (VLBW < 1500？gms) infants, 21% developed at least one episode of culture proven LOS [3]. The most common organisms causing nosocomial infection in neonates include Staphylococcus, Escherichia coli, Klebsiella, and Candida. Coagulase negative staphylococcus (CoNS) is responsible for almost half of the LOS [3, 4]. Neonatal sepsis has been associated with adverse neurological outcomes and poor growth in preterm infants [5–7]. There is an urgent need to identify appropriate strategies to prevent nosocomial
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