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:

Delivery-based criteria for empiric antibiotic administration among preterm infants

Journal of Perinatology volume 41, pages 255–262 (2021)Cite this article

Subjects

Abstract

Objective

Determine impact of using delivery criteria to initiate antibiotics among very low birth weight (VLBW) and extremely low birth weight (ELBW) infants.

Study design

Single site cohort study from 01/01/2009 to 01/31/2020. After 04/2017, infants delivered by Cesarean section, without labor or membrane rupture were categorized as low-risk for early-onset infection and managed without empiric antibiotics. We determined effect of this guideline by pre-post, and interrupted time-series analyses.

Results

After 04/2017, antibiotic initiation ≤3 days decreased among low-risk VLBW (62% vs. 13%, p < 0.001) and low-risk ELBW (88% vs. 21%, p < 0.001) infants. In time series analysis, guideline was associated with decreased initiation among low-risk ELBW infants. In contrast, low-risk VLBW infants demonstrated decreased antibiotic initiation throughout study period. Incidence of confirmed infection, death, or transfer ≤7 days age was unchanged.

Conclusion

Delivery criteria may be used to optimize early antibiotic initiation among preterm infants without short-term increase in adverse outcomes.

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: Change in proportion of infants initiated on antibiotics ≤3 days after birth during study period.

Similar content being viewed by others

References

  1. Fouhy F, Guinane CM, Hussey S, Wall R, Ryan CA, Dempsey EM, et al. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother. 2012;56:5811–20.

    Article  CAS  Google Scholar 

  2. Le J, Nguyen T, Okamoto M, McKamy S, Lieberman JM. Impact of empiric antibiotic use on development of infections caused by extended-spectrum beta-lactamase bacteria in a neonatal intensive care unit. Pediatr Infect Dis J. 2008;27:314–8.

    Article  Google Scholar 

  3. Ting JY, Roberts A, Sherlock R, Ojah C, Cieslak Z, Dunn M, et al. Duration of initial empirical antibiotic therapy and outcomes in very low birth weight infants. Pediatrics. 2019;143. https://doi.org/10.1542/peds.2018-2286.

  4. Kuppala VS, Meinzen-Derr J, Morrow AL, Schibler KR. Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants. J Pediatr. 2011;159:720–5.

    Article  CAS  Google Scholar 

  5. Ting JY, Synnes A, Roberts A, Deshpandey AC, Dow K, Yang J, et al. Association of antibiotic utilization and neurodevelopmental outcomes among extremely low gestational age neonates without proven sepsis or necrotizing enterocolitis. Am J Perinatol. 2018;35:972–8.

    Article  Google Scholar 

  6. Flannery DD, Ross RK, Mukhopadhyay S, Tribble AC, Puopolo KM, Gerber JS. Temporal trends and center variation in early antibiotic use among premature infants. JAMA Netw Open. 2018;1:e180164–e180164.

    Article  Google Scholar 

  7. Puopolo KM, Mukhopadhyay S, Hansen NI, Cotten CM, Stoll BJ, Sanchez PJ, et al. Identification of extremely premature infants at low risk for early-onset sepsis. Pediatrics. 2017;140. https://doi.org/10.1542/peds.2017-0925. Epub 2017 Oct.

  8. Greenberg RG, Chowdhury D, Hansen NI, Smith PB, Stoll BJ, Sanchez PJ, et al. Prolonged duration of early antibiotic therapy in extremely premature infants. Pediatr Res. 2019;85:994–1000.

    Article  Google Scholar 

  9. Benirschke K. Routes and types of infection in the fetus and the newborn. AMA J Dis Child. 1960;99:714–21.

    CAS  PubMed  Google Scholar 

  10. Mukhopadhyay S, Puopolo KM. Clinical and Microbiologic Characteristics of Early-onset Sepsis Among Very Low Birth Weight Infants: Opportunities for Antibiotic Stewardship. Pediatr Infect Dis J. 2017;36:477–81.

    Article  Google Scholar 

  11. Puopolo KM, Benitz WE, Zaoutis TE. Committee on Fetus and Newborn, Committee on Infectious Diseases. Management of neonates born at less than or equal to 34 6/7 weeks’ gestation with suspected or proven early-onset bacterial sepsis. Pediatrics. 2018;142. https://doi.org/10.1542/peds.2018-2896.

  12. Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011;127:817–26.

    Article  Google Scholar 

  13. Mukhopadhyay S, Sengupta S, Puopolo KM. Challenges and opportunities for antibiotic stewardship among preterm infants. Arch Dis Child Fetal Neonatal Ed. 2019;104:F327–32.

    Article  Google Scholar 

  14. Bell MJ. Neonatal necrotizing enterocolitis. N Engl J Med. 1978;298:281–2.

    Article  CAS  Google Scholar 

  15. Caswell JM. Interrupted time series analysis for single series and comparative designs: a guide for beginners with SAS macro. 2019. https://www.academia.edu/35275583/Interrupted_Time_Series_Analysis_for_Single_Series_and_Comparative_Designs_A_Guide_for_Beginners_with_SAS_Macro?sm=b.

  16. Ting JY, Synnes A, Roberts A, Deshpandey A, Dow K, Yoon EW, et al. Association between antibiotic use and neonatal mortality and morbidities in very low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis. JAMA Pediatr. 2016;170:1181–7.

    Article  Google Scholar 

  17. Newman TB, Puopolo KM, Wi S, Draper D, Escobar GJ. Interpreting complete blood counts soon after birth in newborns at risk for sepsis. Pediatrics. 2010;126:903–9.

    Article  Google Scholar 

  18. Christensen RD, Yoder BA, Baer VL, Snow GL, Butler A. Early-onset neutropenia in small-for-gestational-age infants. Pediatrics. 2015;136:e1259–67.

    Article  Google Scholar 

  19. Doron MW, Makhlouf RA, Katz VL, Lawson EE, Stiles AD. Increased incidence of sepsis at birth in neutropenic infants of mothers with preeclampsia. J Pediatr. 1994;125:452–8.

    Article  CAS  Google Scholar 

  20. Teng RJ, Wu TJ, Garrison RD, Sharma R, Hudak ML. Early neutropenia is not associated with an increased rate of nosocomial infection in very low-birth-weight infants. J Perinatol. 2009;29:219–24.

    Article  Google Scholar 

  21. Deshmukh HS, Liu Y, Menkiti OR, Mei J, Dai N, O’Leary CE, et al. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med. 2014;20:524–30.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

SM was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) grant (K23HD088753) and DDF by NICHD/NIH grant (T32HD060550).

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Samuel J. Garber, Miren B. Dhudasia, Dustin D. Flannery, Molly R. Passarella, Karen M. Puopolo & Sagori Mukhopadhyay

  2. Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Samuel J. Garber, Dustin D. Flannery, Karen M. Puopolo & Sagori Mukhopadhyay

  3. Center for Pediatric Clinical Effectiveness, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Miren B. Dhudasia, Dustin D. Flannery, Karen M. Puopolo & Sagori Mukhopadhyay

Authors
  1. Samuel J. Garber
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miren B. Dhudasia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dustin D. Flannery
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Molly R. Passarella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karen M. Puopolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sagori Mukhopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SJG contributed to study design and analytic plan, data collection, reviewed and revised the manuscript. MBD contributed to data collection and management, data analysis and interpretation, reviewed and revised the manuscript. DDF contributed to study design and analytic plan, data collection, reviewed and revised the manuscript. MRP contributed to data analysis and interpretation, reviewed and revised the manuscript. KMP contributed to study design and analytic plan, reviewed and revised the manuscript. SM conceptualized and designed the study, contributed to data collection and analysis, and drafted the first manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Sagori Mukhopadhyay.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garber, S.J., Dhudasia, M.B., Flannery, D.D. et al. Delivery-based criteria for empiric antibiotic administration among preterm infants. J Perinatol 41, 255–262 (2021). https://doi.org/10.1038/s41372-020-00784-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-020-00784-y

This article is cited by

Search

Advanced search

Quick links