Prophylactic probiotic use trends toward decreased incidence of nosocomial infections in preterm infants

Image: PD/CDC

Key study points:

1. Administration of L reuteri to preterm infants was not significantly associated with a reduction in rates of nosocomial infection or death, when compared to placebo; however, there was a trend towards lower rates of pneumonia and necrotizing enterocolitis (NEC) in the probiotic group.

2. L reuteri prophylaxis was associated with decrease in length of hospitalization and episodes of feeding intolerance among infants weighing less than 1500 grams.

Primer: Among many other complications, preterm infants face an increased risk of nosocomial infection and necrotizing NEC due to their immature immune responses and mucosal barriers to invasion. The pathogenesis underlying NEC is not fully understood; however, it is thought bacterial invasion likely plays a role. There has been recent interest in using probiotics (supplements or foods containing beneficial bacterial flora) to protect against pathogenic bacterial invasion of the gastrointestinal (GI) tract. It is believed that probiotics directly compete with attachment of pathogenic organisms to the GI tract and may up-regulate the neonatal immune response against NEC-associated bacteria. The current study aims to determine if the use of prophylactic Lactobacillus reuteri, a naturally occurring human intestinal bacterium, reduces nosocomial infection-associated morbidity and mortality among pre-term infants.

Background reading:

1. Probiotic supplement reduces risk of necrotizing enterocolitis and mortality in preterm very low-birth-weight infants: an updated meta-analysis of 20, randomized controlled trials [Journal of Pediatric Surgery]

2. Probiotics for the prevention of necrotizing enterocolitis in preterm infants (Review) [The Cochrane Collaboration]

3. Lactoferrin for prevention of neonatal infections [Current Opinion in Infectious Disease]

This [double-blinded, randomized, placebo-controlled] study included data from 9 neonatal intensive care units (NICUs) in Colombia from 2008-2011 and is the largest study examining probiotic use in this population. 750 hemodynamically stable preterm infants weighing less than 2000g, less than 2 days old, and admitted to the NICU, were randomized to receive either L reuteri (n = 372) or placebo prophylaxis (n = 380). Primary outcomes included death and nosocomial infection, as indicated by positive blood, urine, or CSF cultures, or evidence of nosocomial pneumonia, NEC, or feeding intolerance.

There was no significant difference in rates of death, nosocomial bloodstream, urinary tract, or CNS infection, pneumonia, or NEC between the group receiving probiotics and the group receiving placebo. Infants weighing less than 1500g and receiving L reuteri experienced significantly fewer episodes of feeding intolerance (9.6% vs. 16.8%, p = .04) and were hospitalized for a significantly shorter time (32 days vs. 37 days, p = .03) than those assigned to the placebo group. Although not statistically significant, there was a 40% decrease in NEC and a trend towards lower rates of pneumonia among those receiving probiotic treatment compared to placebo.

In sum: While the use of L reuteri prophylaxis in the current study was not significantly associated with a decrease in morbidity or mortality secondary to nosocomial infection in preterm infants, there was a trend towards lower rates of pneumonia and necrotizing enterocolitis (NEC) in the probiotic group. A low primary outcome rate (given improved NICU infection control mechanisms) may have underpowered the study, and the possibility of inadequate gut colonization using the current probiotic dosing may have contributed to these insignificant findings. The fact that probiotic administration was associated with fewer episodes of feeding difficulty and decreased lengths of hospital stay among smaller infants implies some benefit from L reuteri use; however, causation cannot be established from the current study. Additional, adequately powered studies should be completed to better define the potential impact of probiotic use. The researchers conclude that their study is consistent with other meta-analyses looking at the beneficial effects of probiotic prophylaxis in preterm infants.

Click to read the study in [Pediatrics]

By [LHC] and [DB]

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