Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants

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Abstract
Necrotising enterocolitis continues to be a problem, particularly in preterm neonates. There have been reports published suggesting that the use of enteral antibiotics may be effective as prophylaxis. This systematic review was undertaken to clarify the issue. To evaluate the benefits and harms of enteral antibiotic prophylaxis for necrotising enterocolitis in low birth weight and preterm infants. Searches were made of the Oxford Database of Perinatal trials, MEDLINE (search terms: necrotizing enterocolitis, antibiotics; newborn infant), previous reviews with cross references, abstracts, conference and symposia proceedings, expert informants and journal handsearching in the fields of Neonatal Pediatrics and Microbiology. All randomized or quasi-randomized controlled trials where enteral antibiotics were used as prophylaxis against NEC in LBW (<2500g) and/or preterm (<37 weeks gestation) infants. The standard method of the Cochrane Collaboration and its Neonatal Review Group was used. The methodological quality of each trial was reviewed by the second author who was blinded to the trial authors and institutions. Each author extracted data separately before comparison and resolution of differences. Relative risk (RR), risk difference (RD), and number needed to treat were used in the analysis. The administration of prophylactic enteral antibiotics resulted in a statistically significant reduction in NEC [RR 0.47 (0.23, 0.98); RD -0.072 (-0.136, -0.008); NNT 13.9 (7.4, 125)]. There was a reduction in NEC-related deaths which was of borderline statistical significance [RR 0.16 (0.02, 1.26); RD -0.097 (-0.183, -0.010); NNT 10.3 (5.46, 100)]. There were no significant differences in all deaths (one trial only) or in NEC-like enteropathies (one trial only). There was a statistically significant increase in the incidence of colonisation with resistant bacteria [RR 1.73 (1.00, 2. 97); RD 0.123 (0.008, 0.238); NNT 8.1 (4.2, 125)]. There is insufficient evidence to support the use of enteral antibiotic prophylaxis for NEC in clinical practice. To address this question further, a large trial would be required with a sample size sufficient to examine all the important benefits and harms. Adverse outcomes associated with infection, particularly with resistant bacteria, should be evaluated.