Establishing enteral feeding in preterm infants with feeding intolerance: a randomized controlled study of low-dose erythromycin. Influence of erythromycin on establishment of feeding in preterm infants: observations from a randomised controlled trial. Erythromycin fails to improve feeding outcome in feeding-intolerant preterm infants. Efficacy of oral erythromycin for treatment of feeding intolerance in preterm infants. Can prophylactic oral erythromycin reduce time to full enteral feeds in preterm neonates? Erythromycin and feeding intolerance in premature infants: a randomized trial. A placebo-controlled trial of low-dose erythromycin to promote feed tolerance in preterm infants. Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants.
A prospective, double-blind, randomized, controlled trial was conducted to evaluate the effect of low-dose erythromycin on the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance.
                Two groups of preterm infants (birth weight </= 1500 g) with feeding intolerance were randomized to either low-dose erythromycin (5 mg/kg every 8 hours) or 5% dextrose placebo, both of which were discontinued 1 week after full enteral feedings were tolerated. The primary outcome variable was the time taken to attain full enteral feedings of at least 130 mL/kg/d.
                The gestational age at birth was similar in the two groups (erythromycin, 27.1 +/- 1.9 weeks; placebo, 27.5 +/- 2.9 weeks). The mean birth weight of the erythromycin group was lower (806.3 +/- 215.6 g) than the placebo group (981.4 +/- 285.4 g; P = 0.18), and included more infants who were small for gestational age (4/13 = 31% versus 1/11 = 9%; P = 0.224). There was no difference between the two groups with regard to the volume of feedings they were receiving at the time of enrollment. Reduction in symptoms of gastroesophageal reflux was similar in the two groups. 3 of 13 in the erythromycin group and 4 of 11 in the placebo group improved during the study (P = 0.565). The mean time to attain full enteral feedings after enrollment was 24.9 + 2.9 days in the erythromycin group and 30.8 +/- 4.1 days in the placebo group, a difference that did not reach statistical significance (P = 0.17).
                Low-dose erythromycin did not reduce the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance. Gastroesophageal reflux decreased as a consequence of maturation of the gastrointestinal tract and not because of erythromycin. These preliminary results justify verification in larger multicenter trials. To determine the effect of erythromycin on the establishment of enteral feeding in ventilated infants < 31 weeks gestation.
                Erythromycin was randomly allocated as an antimicrobial treatment for the first 7 days of life in 76 infants: 35 received erythromycin and 41 acted as controls. Feed toleration, time taken to establish full enteral feeding, vomiting, prescription of glycerine suppositories and occurrence of necrotising enterocolitis were recorded.
                There were no significant differences between the groups for any of the outcomes. The infants treated with erythromycin reached full feeding at a median (quartile) age of 8 (5-12) days compared with 9 (6-14) days for controls.
                Intravenous erythromycin in antimicrobial doses is unlikely to benefit the introduction of feeding in preterm infants. Approximately half of extremely low birth weight infants have feeding intolerance, which delays their achievement of full enteral feedings. Erythromycin, a motilin receptor agonist, triggers migrating motor complexes and accelerates gastric emptying in adults with feeding intolerance. Few studies have assessed the efficacy of this drug in preterm infants with established feeding intolerance. This study was designed to assess the efficacy of erythromycin in feeding-intolerant infants, as measured by gastric emptying, maturation of gastrointestinal motor patterns, and time to achieve full enteral feedings.
                Subjects were 27 preterm infants who were admitted to the neonatal intensive care unit and who did not achieve full enteral feeding volumes (150 mL/kg/day) within 8 days of the initiation of feedings. In a controlled, randomized, double-blinded clinical trial, infants received intragastric erythromycin or placebo for 8 days without crossover. At study entry, the authors recorded motor activity in the antrum and the duodenum during fasting, in response to intragastric erythromycin (1.5 mg/kg) or placebo, and in response to feeding. Gastric emptying at 20 minutes and transit time from duodenum to anus were determined. Each infant then received erythromycin or placebo for 8 days, and feeding characteristics were prospectively tracked.
                Gastric emptying and characteristics of antroduodenal motor contractions were similar in the two groups, as were the transit times from duodenum to anus. Feeding outcomes were comparable in the two groups.
                Intragastric erythromycin does not improve feeding tolerance in preterm infants with established feeding intolerance because it fails to improve gastrointestinal function in the short or long term. To determine the efficacy and safety of oral erythromycin (EM) for feeding intolerance in preterm infants < 35 weeks gestation.
                In this randomized, double-blinded, placebo-controlled trial, preterm infants with feeding intolerance were randomly allocated to a treatment group given EM ethyl succinate 10 mg/kg every 6 hours for 2 days, followed by 4 mg/kg every 6 hours for another 5 days, or to a control group given placebo. The primary outcome was time to full feeding (150 mL/kg/day) after the start of treatment.
                Each group comprised 23 preterm infants, almost all of whom were < 32 weeks gestation. Baseline characteristics were similar between the 2 groups. Times to full feeding were significantly shorter and the number of withheld feeds were significantly less in the EM group than the control group; the respective medians (interquartile ranges) were 7 days (6 to 9 days) versus 13 days (9 to 15 days) (P < .001) and 1 episode (0 to 2 episodes) versus 9 episodes (2 to 13 episodes) (P < .001). No significant differences in episodes of sepsis, necrotizing enterocolitis, and cholestasis were observed.
                Oral EM was effective and safe for treatment of feeding intolerance in preterm infants. Efficacy of oral, prophylactic erythromycin in reducing the time to establish full enteral feeds (150 ml/kg/day) was assessed in neonates < 32 weeks, ready for enteral feeds. Seventy-three consecutive neonates were randomised to receive oral erythromycin ethyl succinate (n = 36) or placebo (n = 37) in a double-blind trial until full enteral feeds or 14 days of therapy were reached. A prospectively designed feeding regimen, including plan of action for signs of feed intolerance, was common for all enrolled neonates. The median gestational age, birth weight and postnatal age at start of feeds were 29 versus 30 weeks (p = 0.40), 1232 versus 1280 g (p = 0.96) and 5 versus 5 days (p = 0.84) for erythromycin and placebo group, respectively. Time to achieve full feeds was not significantly different in the two groups. (median times: erythromycin 93.5 versus placebo 104 hours, p = 0.60). Erythromycin-related side-effects did not occur. To evaluate the effectiveness of low-dose oral erythromycin to treat feeding intolerance in preterm infants.
                This study was a prospective, double-blind, randomized, placebo-controlled trial on 60 premature infants suffering from feeding intolerance. Thirty infants were given oral erythromycin 1 mg/kg every 8 h and 30 infants were given placebo (normal saline). Randomization was stratified on enrollment according to gestational age whether >32 weeks or <or=32 weeks. The primary end point was the length of time taken to establish full enteral feeding since enrollment. Potential adverse effects associated with erythromycin were also monitored. Groups of each corresponding stratum were compared using two-tail t-test and Mann-Whitney for continuous variables, and chi (2) and Fisher's exact for categorical variables.
                For infants with gestational age >32 weeks, the erythromycin group achieved full enteral feeding earlier than placebo group (10.5+/-4.1 vs 16.3+/-5.7 days, respectively; P=0.01) had fewer episodes of gastric residuals (P<0.05) and shorter duration of parenteral nutrition (PN) (P<0.05). On the other hand, in infants with gestational age <or=32 weeks, there were no significant differences between erythromycin and placebo groups regarding any of these variables.
                Low-dose enteral erythromycin is associated with better tolerance of feeding and shorter duration of PN in infants >32 weeks gestation. A similar effect on younger preterm infants was not demonstrable. The aim of this study was to assess the efficacy of erythromycin, a motilin agonist, in promoting enteral feed tolerance in preterm infants of < or = 32 wk gestation. Eligible infants were randomized to receive either low-dose (2.5 mg kg(-1) per dose 6 hourly) oral erythromycin ethylsuccinate or placebo for 10 d from the time of the first oral feed. The data from 22 erythromycin and 21 placebo infants were analysed. Birthweights (erythromycin 1,216 +/- 380 g, placebo 1,355 +/- 228 g, p = 0.25), gestation (erythromycin 28.6 +/- 2.2 wk, placebo 29.3 +/- 1.7 wk, p = 0.24) and other clinical variables were not different between the groups. Almost all infants were fed expressed breast milk. Erythromycin infants had significantly fewer episodes of large residual gastric aspirates (>30% of the previous 6 h worth of feeds) over 10 d (erythromycin 1.1 +/- 1.9, placebo 3.6 +/- 2.2 episodes, p = 0.0007). Infants in the erythromycin group achieved full oral feeds more quickly (6.0 +/- 2.3 vs 7.9 +/- 3.5 d, p = 0.04). There were no significant differences between the groups with regard to the number of days on total parenteral nutrition or to the time needed to regain birthweight. One enrolled infant from each group died of necrotizing enterocolitis.
                Low-dose erythromycin promoted gastric emptying and feed tolerance in premature infants at a lower gestational age than previously reported. Increased exposure to broad-spectrum antibiotics may not be free of risk. Further studies are recommended to assess its efficacy in premature infants with established feed intolerance. To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants.
                A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes.
                Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10 v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms.
                Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage.