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. 2000;2001(2):CD000405.
doi: 10.1002/14651858.CD000405.

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

R G Bury  1 , D Tudehope
Affiliations

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

R G Bury et al. Cochrane Database Syst Rev. 2000.

Update in

Abstract

Background: 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.

Objectives: To evaluate the benefits and harms of enteral antibiotic prophylaxis for necrotising enterocolitis in low birth weight and preterm infants.

Search strategy: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (search terms: necrotizing enterocolitis, antibiotics;

Limits: 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.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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)].

Reviewer's conclusions: 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.

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Conflict of interest statement

None

Figures

1.1
1.1. Analysis
Comparison 1 Enteral aminoglycoside versus control (all studies), Outcome 1 NEC.
1.2
1.2. Analysis
Comparison 1 Enteral aminoglycoside versus control (all studies), Outcome 2 All deaths.
1.3
1.3. Analysis
Comparison 1 Enteral aminoglycoside versus control (all studies), Outcome 3 NEC‐related deaths.
1.4
1.4. Analysis
Comparison 1 Enteral aminoglycoside versus control (all studies), Outcome 4 NEC‐like enteropathies.
1.5
1.5. Analysis
Comparison 1 Enteral aminoglycoside versus control (all studies), Outcome 5 Colonization with resistant bacteria.
2.1
2.1. Analysis
Comparison 2 Enteral aminoglycoside versus control (randomized studies), Outcome 1 NEC.
2.2
2.2. Analysis
Comparison 2 Enteral aminoglycoside versus control (randomized studies), Outcome 2 NEC‐related deaths.
2.3
2.3. Analysis
Comparison 2 Enteral aminoglycoside versus control (randomized studies), Outcome 3 NEC‐like enteropathies.
2.4
2.4. Analysis
Comparison 2 Enteral aminoglycoside versus control (randomized studies), Outcome 4 Colonization with resistant bacteria.
See this image and copyright information in PMC

References

References to studies included in this review

Boyle 1978 {published data only}
    1. Boyle R, Nelson JS, Stonestreet BS, Peter G, Oh W. Alterations in stool flora resulting from oral kanamycin prophylaxis of necrotizing enterocolitis. Journal of Pediatrics 1978;93:857‐61. - PubMed
Egan 1976 {published data only}
    1. Egan EA, Mantilla G, Nelson RM, Eitzmann DV. A prospective controlled trial of oral kanamycin in the prevention of neonatal necrotizng enterocolitis. Journal of Pediatrics 1976;89:467‐70. - PubMed
Grylack 1978 {published data only}
    1. Grylack LJ, Scanlon JW. Oral gentamicin therapy in the prevention of neonatal necrotizing enterocolitis. A controlled double‐blind trial. American Journal of Diseases of Children 1978;132:1192‐4. - PubMed
Rowley 1978 {published data only}
    1. Rowley MP, Dahlenburg GW. Gentamicin in prophylaxis of neonatal necrotizing enterocolitis. Lancet 1978;ii:532. - PubMed
Siu 1998 {published and unpublished data}
    1. Siu YK, Ng PC, Fung SC, Lee CH, Wong MY, Fok TF, So KW, Cheung KL, Wong W, Cheng AF. Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants. Archives of Disease in Childhood Fetal Neonatal Ed 1998;79:F105‐9. - PMC - PubMed

References to studies excluded from this review

Brantley 1980 {published data only}
    1. Brantley VE, Hiatt IM, Hegyi T. The effectiveness of oral gentamicin in reducing the incidence of necrotizing enterocolitis (NEC) in treated and control infants [abstract]. Pediatric Research 1980;14:592 (Abstract).
Faix 1988 {published data only}
    1. Faix RG, Polley TZ, Grasela TH. A randomized, controlled trial of parenteral clindamycin in neonatal necrotizing enterocolitis. Journal of Pediatrics 1988;112:271‐7. - PubMed
Fast 1994 {published data only}
    1. Fast C, Rosegger H. Necrotizing enterocolitis prophylaxis: oral antibiotics and lyophilized enterobacteria vs oral immunoglobulins. Acta Pediatrica 1994;Suppl 396:86‐90. - PubMed
McCaffree 1975 {published data only}
    1. McCaffree MA, Fletcher AB, Avery GB. Prophylactic oral antibiotics in necrotizing enterocolitis [abstract]. Pediatric Research 1975;9:307 (Abstract).
Millar 1992 {published data only}
    1. Millar MR, MacKay P, Levene M, Langdale V, Martin C. Enterobacteriaceae and neonatal necrotising enterocolitis. Archives of Disease in Childhood 1992;67:53‐6. - PMC - PubMed

Additional references

AlFaleh 2005
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Bauer 1992
    1. Bauer CR. Necrotizing enterocolitis. In: Sinclair JC, Bracken MB editor(s). Effective Care of the Newborn Infant. Oxford: Oxford University Press, 1992:602‐14.
Foster 2004
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Henderson 2001a
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Henderson 2001b
    1. Henderson G, Anthony M, McGuire W. Formula milk versus term human milk for feeding preterm or low birth weight infants. Cochrane Database of Systematic Reviews 2001, Issue 4. - PubMed
Kennedy 1998
    1. Kennedy K, Tyson J. Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed low‐birth‐weight infants. Cochrane Database of Systematic Reviews 1998, Issue 4. - PubMed
Kennedy 2000
    1. Kennedy K, Tyson J. Early versus delayed initiation of progressive enteral feedings for parenterally fed low birth weight or preterm infants. Cochrane Database of Systematic Reviews 2000, Issue 1. - PubMed
Shah 2004
    1. Shah P, Shah V. Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database of Systematic Reviews 2004, Issue 4. [DOI: 10.1002/14651858.CD004339.pub2] - DOI - PubMed

References to other published versions of this review

Bury 1998
    1. Bury RG, Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. Cochrane Library 1998, Issue 2. [DOI: 10.1002/14651858.CD000405] - DOI - PubMed
Bury 2000
    1. Bury RG, Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. Cochrane Library 2000, Issue 4. [DOI: 10.1002/14651858.CD000405] - DOI - PubMed
Bury 2002
    1. Bury G, Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. The Cochrane Library 2002, Issue 3. [DOI: 10.1002/14651858.CD000405] - DOI - PubMed

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