Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Variability in antibiotic duration for necrotizing enterocolitis and outcomes in a large multicenter cohort

Journal of Perinatology volume 42, pages 1458–1464 (2022)Cite this article

Subjects

Abstract

Objectives

To evaluate variability in antibiotic duration for necrotizing enterocolitis (NEC) and associated clinical outcomes.

Study design

Five-hundred ninety-one infants with NEC (315 medical; 276 surgical) were included from 22 centers participating in Children’s Hospitals Neonatal Consortium (CHNC). Multivariable analyses were used to determine predictors of variability in time to full feeds (TFF) and length of stay (LOS).

Results

Median (IQR) antibiotic duration was 12 (9, 17) days for medical and 17 (14, 21) days for surgical NEC. Wide variability in antibiotic use existed both within and among centers. Duration of antibiotic therapy was associated with longer TFF in both medical (OR 1.04, 95% CI [1.01, 1.05], p < 0.001) and surgical NEC (OR 1.02 [1, 1.03] p = 0.046); and with longer LOS in medical (OR 1.03 [1.02, 1.04], p < 0.001) and surgical NEC (OR 1.01 [1.01, 1.02], p = 0.002).

Conclusion

Antibiotic duration for both medical and surgical NEC remains variable within and among high level NICUs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Variability in antibiotic duration among participating CHNC centers.
Fig. 2: Relationship between variation in antibiotic prescribing practices and antibiotic duration for treatment of NEC in participating CHNC centers.
Fig. 3: Kaplan–Meier (K–M) analyses.

Similar content being viewed by others

Data availability

All data relevant to the study are included in the article. Requests for additional material can be made to IA at iahmad@choc.org.

References

  1. Horbar JD, Carpenter JH, Badger GJ, Kenny MJ, Soll RF, Morrow KA, et al. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics. 2012;129:1019–26.

    Article  PubMed  Google Scholar 

  2. Johnson TJ, Patel AL, Jegier BJ, Engstrom JL, Meier PP. Cost of morbidities in very low birth weight infants. J Pediatr. 2013;162:243–49.e1.

    Article  PubMed  Google Scholar 

  3. Yee WH, Soraisham AS, Shah VS, Aziz K, Yoon W, Lee SK, et al. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics. 2012;129:e298–304.

    Article  PubMed  Google Scholar 

  4. Shulhan J, Dicken B, Hartling L, Larsen BM. Current knowledge of necrotizing enterocolitis in preterm infants and the impact of different types of enteral nutrition products. Adv Nutr. 2017;8:80–91.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 2016;13:590–600.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006;368:1271–83.

    Article  PubMed  Google Scholar 

  7. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364:255–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Neu J, Pammi M. Necrotizing enterocolitis: the intestinal microbiome, metabolome and inflammatory mediators. Semin Fetal Neonatal Med. 2018;23:400–5.

    Article  PubMed  Google Scholar 

  9. Neu J. Necrotizing enterocolitis: the mystery goes on. Neonatology. 2014;106:289–95.

    Article  CAS  PubMed  Google Scholar 

  10. Blackwood BP, Hunter CJ, Grabowski J. Variability in antibiotic regimens for surgical necrotizing enterocolitis highlights the need for new guidelines. Surg Infect. 2017;18:215–20.

    Article  Google Scholar 

  11. Murphy C, Nair J, Wrotniak B, Polischuk E, Islam S. Antibiotic treatments and patient outcomes in necrotizing enterocolitis. Am J Perinatol. 2020;37:1250–7.

    Article  PubMed  Google Scholar 

  12. Gibson MK, Crofts TS, Dantas G. Antibiotics and the developing infant gut microbiota and resistome. Curr Opin Microbiol. 2015;27:51–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jasani B, Patole S. Standardized feeding regimen for reducing necrotizing enterocolitis in preterm infants: an updated systematic review. J Perinatol. 2017;37:827–33. https://doi.org/10.1038/jp.2017.37.

    Article  CAS  PubMed  Google Scholar 

  14. Murthy K, Dykes FD, Padula MA, Pallotto EK, Reber KM, Durand DJ, et al. The Children’s Hospitals Neonatal Database: an overview of patient complexity, outcomes and variation in care. J Perinatol. 2014;34:582–6.

    Article  CAS  PubMed  Google Scholar 

  15. Shah D, Sinn JK. Antibiotic regimens for the empirical treatment of newborn infants with necrotising enterocolitis. Cochrane Database Syst Rev. 2012:CD007448. https://doi.org/10.1002/14651858.CD007448.pub2.

  16. Morowitz MJ, Poroyko V, Caplan M, Alverdy J, Liu DC. Redefining the role of intestinal microes in the pathogenesis of necrotizing enterocolitis. Pediatrics. 2010;125:777–85.

    Article  PubMed  Google Scholar 

  17. Coggins SA, Wynn JL, Weitkamp JH. Infectious causes of necrotizing enterocolitis. Clin Perinatol. 2015;42:133–54.

    Article  PubMed  Google Scholar 

  18. Bizzarro MJ, Ehrenkranz RA, Gallagher PG. Concurrent bloodstream infections in infants with necrotizing enterocolitis. J Pediatr. 2014;164:61–6.

    Article  PubMed  Google Scholar 

  19. Clark RH, Gordon P, Walker WM, Laughon M, Smith PB, Spitzer AR. Characteristics of patients who die of necrotizing enterocolitis. J Perinatol. 2012;32:199–204.

    Article  CAS  PubMed  Google Scholar 

  20. Mollitt DL, Tepas JJ, Talbert JL. The microbiology of neonatal peritonitis. Arch Surg. 1988;123:176–9.

    Article  CAS  PubMed  Google Scholar 

  21. Smith B, Bodé S, Petersen BL, Jensen TK, Pipper C, Kloppenborg J, et al. Community analysis of bacteria colonizing intestinal tissue of neonates with necrotizing enterocolitis. BMC Microbiol. 2011;11:73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Good M, Sodhi CP, Hackam DJ. Evidence-based feeding strategies before and after the development of necrotizing enterocolitis. Expert Rev Clin Immunol. 2014;10:875–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Arbra CA, Oprisan A, Wilson DA, Ryan RM, Lesher AP. Time to reintroduction of feeding in infants with nonsurgical necrotizing enterocolitis. J Pediatr Surg. 2018;53:1187–91.

    Article  PubMed  Google Scholar 

  24. Bohnhorst B, Müller S, Dördelmann M, Peter CS, Petersen C, Poets CF. Early feeding after necrotizing enterocolitis in preterm infants. J Pediatr. 2003;143:484–7.

    Article  PubMed  Google Scholar 

  25. Brotschi B, Baenziger O, Frey B, Bucher HU, Ersch J. Early enteral feeding in conservatively managed stage II necrotizing enterocolitis is associated with a reduced risk of catheter-related sepsis. J Perinat Med. 2009;37:701–5.

    Article  PubMed  Google Scholar 

  26. Hock AM, Chen Y, Miyake H, Koike Y, Seo S, Pierro A. Initiation of enteral feeding after necrotizing enterocolitis. Eur J Pediatr Surg. 2018;28:44–50.

    Article  PubMed  Google Scholar 

  27. Patel EU, Wilson DA, Brennan EA, Lesher AP, Ryan RM. Earlier re-initiation of enteral feeding after necrotizing enterocolitis decreases recurrence or stricture: a systemis review and meta-analysis. J Perinatol. 2020;40:1679–87.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Cheah IGS. Economic assessment of neonatal intensive care. Transl Pediatr. 2019;8:246–56.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Schimpl G, Höllwarth ME, Fotter R, Becker H. Late intestinal strictures following successful treatment of necrotizing enterocolitis. Acta Paediatr Suppl. 1994;396:80–3.

    Article  CAS  PubMed  Google Scholar 

  30. Phad N, Trivedi A, Todd D, Lakkundi A. Intestinal strictures post-necrotising enterocolitis: clinical profile and risk factors. J Neonatal Surg. 2014;3:44.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Schwartz MZ, Hayden CK, Richardson CJ, Tyson KR, Lobe TE. A prospective evaluation of intestinal stenosis following necrotizing enterocolitis. J Pediatr Surg. 1082;17:764–70.

  32. Janik JS, Ein SH, Mancer K. Intestinal stricture after necrotizing enterocolitis. J Pediatr Surg. 1981;16:438–43.

    Article  CAS  PubMed  Google Scholar 

  33. Zhang H, Chen J, Wang Y, Deng C, Li L, Guo C. Predictive factors and clinical practice profile for strictures post-necrotising enterocolitis. Medicine. 2017;96:e6273.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Pammi M, Cope J, Tarr PI, Warner BB, Morrow AL, Mai V, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome. 2017;5:31.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Warner BB, Deych E, Zhou Y, Hall-Moore C, Weinstock GM, Sodergren E, et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet. 2016;387:1928–36.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis. J Antimicrob Chemother. 2017;72:1858–70.

    Article  CAS  PubMed  Google Scholar 

  37. Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sánchez PJ, et al. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics. 2009;123:58–66.

    Article  PubMed  Google Scholar 

  38. Miller J, Tonkin E, Damarell RA, McPhee AJ, Suganuma M, Suganuma H, et al. A systematic review and meta-analysis of human milk feeding and morbidity in very low birth weight infants. Nutrients. 2018;10:707.

  39. Andorsky DJ, Lund DP, Lillehei CW, Jaksic T, Dicanzio J, Richardson DS, et al. Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes. J Pediatr. 2001;139:27–33.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Jeanette Asselin, David Durand (ex officio), Francine Dykes (ex officio), Jacquelyn Evans, Karna Murthy (Chair), Michael Padula, Eugenia Pallotto, Theresa Grover, Beverly Brozanski, and Anthony Piazza, Kristina Reber and Billie Short are members of the Children’s Hospitals Neonatal Consortium, Inc. For more information, please contact: support@thechnc.org. We are indebted to the following institutions that serve the infants and their families, and these institutions also have invested in and continue to participate in the Children’s Hospital’s Neonatal Database (CHND). The site sponsors/contributors for the CHND are also included: 1. Children’s Healthcare of Atlanta, Atlanta, GA (Francine Dykes, Anthony Piazza). 2. Children’s Healthcare of Atlanta at Scottish Rite (Gregory Sysyn). 3. Children’s Hospital of Alabama, Birmingham, AL (Carl Coghill, Allison Black). 4. Le Bonheur Children’s Hospital, Memphis, TN (Ramasubbareddy Dhanireddy). 5. Children’s Hospital Boston, Boston, MA (Anne Hansen, Tanzeema Houssain). 6. Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL (Karna Murthy, Gustave Falciglia). 7. Cincinnati Children’s Hospital, Cincinnati, OH (Beth Haberman, Breda Poindexter, Amy Nathan, Kristin Nelson, Paul Kingma, Stefanie Riddle, Stephanie Merhar). 8. Nationwide Children’s Hospital, Columbus, OH (Kristina Reber). 9. Children’s Medical Center, Dallas, TX (Rashmin Savani, Luc Brion, Noorjahan Ali). 10. Children’s Hospital Colorado, Aurora, CO (Theresa Grover). 11. Children’s Hospital of Michigan, Detroit, MI (Girija Natarajan). 12. Cook Children’s Health Care System, Fort Worth, TX (Jonathan Nedrelow, Annie Chi, Yvette Johnson). 13. Texas Children’s Hospital, Houston, TX (Gautham Suresh). 14. Riley Children’s Hospital, Indianapolis, IN (William Engle, Lora Simpson, Gregory Sokol). 15. Children’s Mercy Hospitals & Clinics, Kansas City, MO (Eugenia Pallotto). 16. Arkansas Children’s Hospital, Little Rock, AR (Robert Lyle, Becky Rogers). 17. Children’s Hospital Los Angeles, Los Angeles, CA (Steven Chin, Rachel Chapman). 18. American Family Children’s Hospital, Madison, WI (Jamie Limjoco, Lori Haack). 19. Children’s Hospital & Research Center Oakland, Oakland, CA (David Durand, Jeanette Asselin, Art D’Harlingue, Priscilla Joe). 20. The Children’s Hospital of Philadelphia, Philadelphia, PA (Jacquelyn Evans, Michael Padula, David Munson). 21. Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (Toby Yanowitz). 22. St. Louis Children’s Hospital, St Louis, MO (Tasmin Najaf, Rakesh Rao). 23. All Children’s Hospital, St. Petersburg, FL (Victor McKay). 24. Rady Children’s Hospital, San Diego, CA (Mark Speziale, Brian Lane, Laural Moyer). 25. Children’s National Medical Center, Washington, DC (Billie Short). 26. AI DuPont Hospital for Children, Wilmington, DE (Kevin Sullivan). 27. Primary Children’s Medical Center, Salt Lake City, UT (Con Yee Ling, Shrena Patel). 28. Children’s Hospital of Wisconsin, Milwaukee, WI (Michael Uhing, Ankur Datta). 29. Children’s Hospital of Omaha (Lynne Willett, Nicole Birge). 30. Florida Hospital for Children (Rajan Wadhawan). 31. Seattle Children’s Hospital, Seattle, WA (Elizabeth Jacobsen-Misbe, Robert DiGeronimo, Zeenia Billimoria). 32. Hospital for Sick Children, Toronto, ON (Kyong-Soon Lee).

Author information

Authors and Affiliations

  1. CHOC Children’s Hospital, Orange, CA, USA

    Irfan Ahmad

  2. Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Muralidhar H. Premkumar, Amy B. Hair & Kristina M. Reber

  3. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA

    Kevin M. Sullivan

  4. Children’s Hospital Association, Lenexa, KS, USA

    Isabella Zaniletti

  5. University of Missouri Kansas City School of Medicine, Kansas City, MO, USA

    Jotishna Sharma

  6. University of Texas Southwestern, Dallas, TX, USA

    Sujir Pritha Nayak

  7. University of Pennsylvania, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Michael Padula

  8. Washington University School of Medicine, St. Louis, MO, USA

    Beverly Brozanski

  9. University of Washington School of Medicine, Seattle, WA, USA

    Robert DiGeronimo

  10. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Toby Debra Yanowitz

  11. CHOC Children’s Hospital, Orange, CA, USA

    Irfan Ahmad

  12. Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Muralidhar H. Premkumar, Amy B. Hair & Kristina M. Reber

  13. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA

    Kevin M. Sullivan

  14. University of Missouri Kansas City School of Medicine, Kansas City, MO, USA

    Jotishna Sharma

  15. University of Texas Southwestern, Dallas, TX, USA

    Sujir Pritha Nayak

  16. University of Pennsylvania, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Michael Padula

  17. Washington University School of Medicine, St. Louis, MO, USA

    Beverly Brozanski

  18. University of Washington School of Medicine, Seattle, WA, USA

    Robert DiGeronimo

  19. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Toby Debra Yanowitz

Authors
  1. Irfan Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muralidhar H. Premkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amy B. Hair
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kevin M. Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isabella Zaniletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jotishna Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sujir Pritha Nayak
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kristina M. Reber
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael Padula
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Beverly Brozanski
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Robert DiGeronimo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toby Debra Yanowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Children’s Hospitals Neonatal Consortium NEC Focus Group

  • Irfan Ahmad
  • , Muralidhar H. Premkumar
  • , Amy B. Hair
  • , Kevin M. Sullivan
  • , Jotishna Sharma
  • , Sujir Pritha Nayak
  • , Kristina M. Reber
  • , Michael Padula
  • , Beverly Brozanski
  • , Robert DiGeronimo
  •  & Toby Debra Yanowitz

Contributions

All authors contributed intellectually to the conception of the study and provided critical inputs during the CHNC NEC work group meetings. IZ conducted data analysis, IA and TY drafted the initial manuscript, and all authors helped revised the manuscript as well as reviewed the final version.

Corresponding author

Correspondence to Irfan Ahmad.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Members of the Children’s Hospitals Neonatal Consortium NEC Focus Group are listed below Acknowledgements.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmad, I., Premkumar, M.H., Hair, A.B. et al. Variability in antibiotic duration for necrotizing enterocolitis and outcomes in a large multicenter cohort. J Perinatol 42, 1458–1464 (2022). https://doi.org/10.1038/s41372-022-01433-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-022-01433-2

This article is cited by

Search

Advanced search

Quick links