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Am J Perinatol 2023; 40(06): 646-656
DOI: 10.1055/s-0041-1730364
Original Article

Empirical Antimicrobial Therapy of Neonates with Necrotizing Enterocolitis: A Systematic Review

Daniele Donà
1   Division of Paediatric Infectious Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy
,
Andrea Gastaldi 
2   Department of Pediatrics, Woman and Child Hospital, University of Verona, Verona, Italy
,
Elisa Barbieri
1   Division of Paediatric Infectious Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy
,
Luca Bonadies
3   Neonatal Intensive Care Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy
,
Jalemba Aluvaala
4   Health Services Unit, KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
5   Department of Paediatrics, University of Nairobi, Nairobi, Kenya
,
Mike English
4   Health Services Unit, KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
6   Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom
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Abstract

Objective Necrotizing enterocolitis (NEC) is an inflammatory disease of the gastrointestinal tract characterized by ischemic necrosis of the intestinal mucosa, mostly affecting premature neonates. Management of NEC includes medical care and surgical approaches, with supportive care and empirical antibiotic therapy recommended to avoid any disease progression. However, there is still no clear evidence-based consensus on empiric antibiotic strategies or surgical timing. This study was aimed to review the available evidence on the effectiveness and safety of different antibiotic regimens for NEC.

Study Design MEDLINE, EMBASE, Cochrane CENTRAL, and CINAHL databases were systematically searched through May 31, 2020. Randomized controlled trials (RCTs) and nonrandomized interventions reporting data on predefined outcomes related to NEC treatments were included. Clinical trials were assessed using the criteria and standard methods of the Cochrane risk of bias tool for randomized trials, while the risk of bias in nonrandomized studies of interventions was evaluated using the ROBINS-I tool. The certainty in evidence of each outcome's effects was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results Five studies were included in this review, two RCTs and three observational studies, for a total amount of 3,161 patients. One RCT compared the outcomes of parenteral (ampicillin plus gentamicin) and oral (gentamicin) treatment with parenteral only. Three studies (one RCT and two observational) evaluated adding anaerobic coverage to different parenteral regimens. The last observational study compared two different parenteral antibiotic combinations (ampicillin and gentamicin vs. cefotaxime and vancomycin).

Conclusion No antimicrobial regimen has been shown to be superior to ampicillin and gentamicin in decreasing mortality and preventing clinical deterioration in NEC. The use of additional antibiotics providing anaerobic coverage, typically metronidazole, or use of other broad-spectrum regimens as first-line empiric therapy is not supported by the very limited current evidence. Well-conducted, appropriately sized comparative trials are needed to make evidence-based recommendations.

Key Points

  • Ampicillin and gentamicin are effective in decreasing mortality and preventing clinical deterioration in NEC.

  • Metronidazole could be added in patients with surgical NEC.

  • No study with high-quality evidence was found.

Keywords

necrotizing enterocolitis - empiric antibiotic therapy - systematic review - neonate - VLBW

Authors' Contributions

All authors have participated in the concept and design, analysis and interpretation of data, drafting or revising of the manuscript, and they have approved the manuscript as submitted.


Supplementary Material



Publikationsverlauf

Eingereicht: 27. Oktober 2020

Angenommen: 16. April 2021

Artikel online veröffentlicht:
14. Juni 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

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