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Am J Perinatol 2025; 42(16): 2169-2175
DOI: 10.1055/a-2568-7085
Original Article

Early Effective Antibiotic Therapy and Meningitis following a Bloodstream Infection in Hospitalized Infants: A Cohort Study

Authors

  • Jessica E. Ericson 

    1   Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania

  • Rachel G. Greenberg 

    2   Department of Pediatrics, Duke Clinical Research Institute, Durham, North Carolina
    3   Department of Pediatrics, Duke University, Durham, North Carolina

  • P. Brian Smith

    2   Department of Pediatrics, Duke Clinical Research Institute, Durham, North Carolina
    3   Department of Pediatrics, Duke University, Durham, North Carolina

  • Reese H. Clark

    4   Center for Research, Education, Quality, and Safety, Pediatrix-Obstetrix Research Center, Sunrise, Florida

  • Daniel K. Benjamin Jr.

    2   Department of Pediatrics, Duke Clinical Research Institute, Durham, North Carolina
    3   Department of Pediatrics, Duke University, Durham, North Carolina

  • Ryan Kilpatrick 

    5   Division of Newborn Medicine, Tufts University School of Medicine, Boston, Massachusetts

Funding This research is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health [5UL1TR002014 and 5KL2 TR002015 to J.E.E.]; the National Institutes of Health [HHSN 275201000003I, HHSN 272201300017I, HHSN200201253663 to R.G.G.]; and The Food and Drug Administration [HHSF223201610082C to R.G.G.].). This work was funded, in part by the Kiser-Arena Professorship at Duke University and was funded under the Best Pharmaceuticals for Children Act and National Institute of Child Health and Human Development (NICHD) contract HHSN275201000003I for the Pediatric Trials Network (Principal Investigator: D.K.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Abstract

Objective

This study aimed to evaluate the role of early effective antibiotic therapy in preventing secondary meningitis as a sequelae of bacterial bloodstream infections (BSI).

Study Design

In this multicenter cohort study, we identified blood cultures that were positive for Group B Streptococcus (GBS), Staphylococcus aureus, Escherichia coli, and other non-E. coli gram-negative bacteria that had a corresponding cerebrospinal fluid sample collected ≤7 days after the positive blood culture among infants discharged from a neonatal intensive care unit managed by the Pediatrix Medical Group 2002 to 2020. The odds of secondary meningitis for early effective antibiotic therapy versus delayed antibiotic therapy were compared using an adjusted logistic regression model. The odds of secondary meningitis following GBS BSI were compared for infections treated with empirical vancomycin versus β-lactam antibiotic.

Results

Secondary meningitis was identified in 11% of 5,967 BSI. Early effective antibiotic therapy was not associated with a reduced odds of secondary meningitis for GBS (adjusted odds ratio [aOR]: 1.17; 95% confidence interval [CI]: 0.82–1.66) or E. coli (aOR: 1.06; 95% CI: 0.82–1.38); however, was associated with decreased odds for non-E. coli gram-negative bacteria (aOR: 0.69; 95% CI: 0.49–0.98) and S. aureus (aOR: 0.51; 95% CI: 0.34–0.74). GBS BSIs were more often complicated by meningitis when vancomycin was used empirically compared with β-lactam antibiotic (aOR: 2.01; 95% CI: 1.28–3.14).

Conclusion

Early effective antibiotic therapy for BSI in infants did not reduce the odds of secondary meningitis caused by GBS or E. coli; however, early effective antibiotic therapy did reduce episodes due to non-E. coli gram-negative bacteria and S. aureus.

Key Points

  • Early effective antibiotic therapy in the setting of non-E. coli gram-negative bacteria and S. aureus BSI was associated with reduced odds of secondary meningitis.

  • Early effective antibiotic therapy for BSI in infants was not found to reduce the odds of secondary meningitis caused by GBS or E. coli.

  • GBS BSIs were more commonly complicated by meningitis when vancomycin was used empirically compared with a β-lactam antibiotic.

Keywords

neonate - infection - sepsis - meningitis - antibiotics


Publication History

Received: 15 February 2025

Accepted: 27 March 2025

Accepted Manuscript online:
28 March 2025

Article published online:
29 April 2025

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