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5.7 Antibiotics for treatment of necrotizing enterocolitis
Young neonates with suspected necrotizing enterocolitis NEC should be treated with IV or IM ampicillin or penicillin and gentamicin as a irst line antibiotic
treatment for 10 days.
Standard recommendation, low quality evidence
Remarks he panel noted that it has been common practice to add metronidazole to the
treatment of NEC. Although there is no evidence to judge its beneits, metronidazole covers gastrointestinal tract anaerobic bacteria such as Bacteroides fragilus. It also
noted that while a combination of vancomycin and cetriaxone is a suitable alternative, the only evidence is from tertiary western intensive care units. Vancomycin and 3rd
generation cephalosporins are expensive, and would not be feasible to use as a irst line antibiotic treatment for NEC in low-resource settings.
5.7.1 Evidence and summary of findings
NEC is a serious disease characterized by varying degrees of mucosal necrosis, seen predominantly in premature infants. he underlying pathogenesis remains unclear
and pathogenic organisms are not isolated in many cases. Clustering of cases and outbreaks in nurseries suggest an infective component to its aetiology.
Four studies were found directly comparing antibiotic regimens in NEC. One non-concurrent cohort study from Belgium was excluded as the efect of the addition
of metronidazole to an existing antibiotic regimen could not be separated from other simultaneous modiications to an existing management protocol e.g. earlier and
diferent surgical approaches, changes in anaesthesia, and modiication of intensive care management routines.
One study included 46 cases of NEC in 1982–3 treated with ampicillin and gentamicin, and 44 cases in 1984–5 treated with vancomycin and cetriaxone
[Scheifele, 1987]. here were no statistical diferences in any measured outcomes for infants of birth weight 2200g and complications were infrequent in both groups.
For infants 2200g, those treated with Vancomycin demonstrated statistically lower rates of death p = 0.048, need for surgery p = 0.04, culture positive peritonitis p =
0.01, and major complications p = 0.004: these included peritonitis, strictures, feed intolerance, and recurrent NEC and thrombocytopenia. he quality of evidence was
graded as very low.
One RCT allocated 42 premature infants with radiographically conirmed NEC to receive IV ampicillin and gentamicin or to receive ampicillin, gentamicin,
and clindamycin [Faix, 1998]. his study found an increased rate of complicating strictures in the clindamycin group NNT harm 3, 95 CI 2 to 13 with a consequently
longer time needed to restart feeds 8.4 days versus 22.3. here were no signiicant diferences in rates of death or in incidence of gangreneperforation. he study was
terminated early due to signiicantly higher rates of strictures in the clindamycin group. he quality of evidence was graded as low
see GRADE table A7.5 .
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One RCT allocated 20 infants with NEC to receive ampicillin and gentamicin versus IV ampicillin and gentamicin with oral gentamicin for 4 days [Hansen, 1987].
In this study, enrolled infants were more mature ampicillin and gentamicin 34.7±1.3 weeks gestation and ampicillin and gentamicin with oral gentamicin 35.6±1.1 weeks
and higher birth weight ampicillin and gentamicin 2220±295g and ampicillin and gentamicin with oral gentamicin 2180±198g than many studies reporting NEC.
his study found no signiicant diferences in outcomes p 0.05, including days with peritonitis, days with pneumatosis, major complications including perforation,
stricture and ileus, and death. his study was underpowered to detect most diferences, with blinding and allocation concealment not well deined. he quality
of this evidence was graded as low.
5.7.2 Benefits and risks
Benefits Vancomycin and cetriaxone may be better than ampicillin and gentamicin for
treatment of NEC but the conidence in this statement is low, because factors other than antibiotics may have resulted in or contributed to the beneicial efect as the
study was a non-concurrent study. here is no evidence to judge the beneits of metronidazole.
Risks Clindamycin was administered in one study to cover gram negative organisms and
resulted in a signiicantly higher rate of stricture formation. here is no evidence to judge the risks of metronidazole.
5.7.3 Acceptability and feasibility
A combination of vancomycin and cetriaxone may not be feasible and may be expensive to use as a irst line antibiotic treatment in infants with NEC.
5.8 Kangaroo Mother Care
Low birth weight LBW neonates weighing 2000 g who are clinically stable should be provided Kangaroo Mother Care KMC early in the irst week of life.
Strong recommendation, moderate quality evidence
he panel noted that although there is no evidence for KMC in babies 2000 g, KMC may be beneicial in neonates who have temperature instability. However,
implementation will require a description on how to provide KMC.
5.8.1 Evidence and summary of recommendations
We identiied one recent systematic review [Lawn, 2010] which aimed to assess the efect on neonatal mortality and morbidity from complications of preterm birth of
KMC compared to no care at all or compared to conventional care. A preterm death was deined as a neonatal death in a baby with a birth weight 2000 g. KMC was
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