Israel Medical Association Journal

Acute otitis externa (AOE) is typically a bacterial infection of the external auditory canal, which is most commonly caused by Pseudomonas aeruginosa. Although AOE occurs in all age groups, it is rarely observed in children under 2 years of age [1]. Ear drainage in a neonate is a relatively uncommon finding in the neonatal intensive care unit (NICU) population. This diagnosis requires confirmation by otoscopy [2,3].

Osteomyelitis of the temporal bone, also referred to as necrotizing otitis externa, is a severe form of infection that may develop typically in diabetic or immunocompromised patients, including premature infants. Similar to simple AOE, Pseudomonas aeruginosa is the most common pathogen [4,5]. In the NICU setting it mostly causes infection in immunocompromised hosts such as premature infants [3].

Background: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts.

Objectives: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding.

Methods: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26–33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels.

Results: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59–8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20–9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29–2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group.

Conclusions: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26–33 weeks.