Risk factors for prolonged infection and secondary infection in pediatric severe sepsis

Zachary Aldewereld; Brendan Connolly; Russell K Banks; Ron Reeder; Richard Holubkov; Robert A Berg; David Wessel; Murray M Pollack; Kathleen Meert; Mark Hall; Christopher Newth; John C Lin; Allan Doctor; Tim Cornell; Rick E Harrison; Athena F Zuppa; J Michael Dean; Joseph A Carcillo

doi:10.1007/s15010-024-02355-1

Risk factors for prolonged infection and secondary infection in pediatric severe sepsis

Infection. 2024 Aug 8. doi: 10.1007/s15010-024-02355-1. Online ahead of print.

Authors

Zachary Aldewereld^{1

2}, Brendan Connolly³, Russell K Banks⁴, Ron Reeder⁴, Richard Holubkov⁴, Robert A Berg⁵, David Wessel⁶, Murray M Pollack⁶, Kathleen Meert^{7

8}, Mark Hall⁹, Christopher Newth¹⁰, John C Lin¹¹, Allan Doctor¹¹, Tim Cornell¹², Rick E Harrison¹³, Athena F Zuppa⁵, J Michael Dean⁴, Joseph A Carcillo¹⁴

Affiliations

¹ Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh, 4401 Penn Ave, FP Suite 2000, Pittsburgh, PA, 15224, USA. [email protected].
² Division of Pediatric Infectious Diseases, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. [email protected].
³ University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁴ Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
⁵ Department of Anesthesiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Division of Critical Care Medicine, Department of Pediatrics, Children's National Hospital, Washington, DC, USA.
⁷ Division of Critical Care Medicine, Department of Pediatrics, Children's Hospital of Michigan, Detroit, MI, USA.
⁸ College of Medicine, Central Michigan University, Mt Pleasant, MI, USA.
⁹ Division of Critical Care Medicine, Department of Pediatrics, The Research Institute at Nationwide Children's Hospital Immune Surveillance Laboratory, and Nationwide Children's Hospital, Columbus, OH, USA.
¹⁰ Division of Pediatric Critical Care Medicine, Department of Anesthesiology and Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA.
¹¹ Division of Critical Care Medicine, Department of Pediatrics, St. Louis Children's Hospital, St. Louis, MO, USA.
¹² Division of Critical Care Medicine, Department of Pediatrics, C. S. Mott Children's Hospital, Ann Arbor, MI, USA.
¹³ Division of Critical Care Medicine, Department of Pediatrics, Mattel Children's Hospital at University of California Los Angeles, Los Angeles, CA, USA.
¹⁴ Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh, 4401 Penn Ave, FP Suite 2000, Pittsburgh, PA, 15224, USA. [email protected].

PMID: 39117931
DOI: 10.1007/s15010-024-02355-1

Abstract

Purpose: Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications.

Methods: We performed a secondary analysis of clinical data from 401 subjects enrolled in the PHENOtyping sepsis-induced Multiple organ failure Study. We examined factors associated with prolonged infection, defined as infection that continued to be identified 7 days or more from initial identification, and secondary infection, defined as new infections identified ≥ 3 days from presentation. Multivariable adjustment was performed to examine laboratory markers of immune depression, with immunocompromised and immunocompetent subjects analyzed separately.

Results: Illness severity, immunocompromised status, invasive procedures, and site of infection were associated with secondary infection and/or prolonged infection. Persistent lymphopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL twice in the first five days, and persistent neutropenia, defined as absolute neutrophil count (ANC) < 1000 cells/µL twice in the first five days, were associated with secondary and prolonged infections. When adjusted in multivariable analysis, persistent lymphopenia remained associated with secondary infection in both immunocompromised (aOR = 14.19, 95% CI [2.69, 262.22] and immunocompetent subjects (aOR = 2.09, 95% CI [1.03, 4.17]). Persistent neutropenia was independently associated with secondary infection in immunocompromised subjects (aOR = 5.34, 95% CI [1.92, 15.84]). Secondary and prolonged infections were associated with worse outcomes, including death.

Conclusions: Laboratory markers of immune suppression can be used to predict secondary infection. Lymphopenia is an independent risk factor in immunocompromised and immunocompetent patients for secondary infection.

Keywords: Lymphopenia; Neutropenia; Prolonged infection; Secondary infection; Sepsis.

Abstract

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