Abstract
Background
Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores.
Methods
We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment.
Results
Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8–20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference −0.07, 95% CI −0.92 to 0.79, p = 0.88).
Conclusions
We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment.
Impact
-
In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h.
-
Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures.
-
Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research.
Similar content being viewed by others
Data availability
The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.
References
Gray, J., Gossain, S. & Morris, K. Three-year survey of bacteremia and fungemia in a pediatric intensive care unit. Pediatr. Infect. Dis. J. 20, 416–421 (2001).
Kumar, A. et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit. Care Med. 34, 1589–1596 (2006).
Weiss, S. L. et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit. Care Med. 42, 2409–2417 (2014).
Seymour, C. W. et al. Time to treatment and mortality during mandated emergency care for sepsis. N. Engl. J. Med. 376, 2235–2244 (2017).
Peltan, I. D. et al. ED door-to-antibiotic time and long-term mortality in sepsis. Chest 155, 938–946 (2019).
Liu, V. X. et al. The timing of early antibiotics and hospital mortality in sepsis. Am. J. Respir. Crit. Care Med. 196, 856–863 (2017).
Evans, I. V. R. et al. Association between the New York sepsis care mandate and in-hospital mortality for pediatric sepsis. JAMA 320, 358–367 (2018).
Burns, J. P., Sellers, D. E., Meyer, E. C., Lewis-Newby, M. & Truog, R. D. Epidemiology of death in the PICU at five U.S. teaching hospitals. Crit. Care Med. 42, 2101–2108 (2014).
Pollack, M. M. et al. Simultaneous prediction of new morbidity, mortality, and survival without new morbidity from pediatric intensive care: a new paradigm for outcomes assessment. Crit. Care Med. 43, 1699–1709 (2015).
Pong, S. et al. Antimicrobial treatment duration for uncomplicated bloodstream infections in critically ill children: a multicentre observational study. BMC Pediatr. 22, 179 (2022).
Proulx, F., Fayon, M., Farrell, C. A., Lacroix, J. & Gauthier, M. Epidemiology of sepsis and multiple organ dysfunction syndrome in children. Chest 109, 1033–1037 (1996).
Leclerc, F. et al. Cumulative influence of organ dysfunctions and septic state on mortality of critically ill children. Am. J. Respir. Crit. Care Med. 171, 348–353 (2005).
Leteurtre, S. et al. PELOD-2: an update of the PEdiatric logistic organ dysfunction score. Crit. Care Med. 41, 1761–1773 (2013).
Karam, O. et al. Performance of the PEdiatric Logistic Organ Dysfunction-2 score in critically ill children requiring plasma transfusions. Ann. Intensive Care 6, 98 (2016).
Leteurtre, S. et al. Daily estimation of the severity of organ dysfunctions in critically ill children by using the PELOD-2 score. Crit. Care 19, 324 (2015).
National Healthcare Safety Network. National Healthcare Safety Network (NHSN) patient safety component manual. https://www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual_current.pdf (2022).
Pollack, M. M. et al. The Pediatric Risk of Mortality Score: update 2015. Pediatr. Crit. Care Med. 17, 2–9 (2016).
Allan, V. et al. Propensity score matching and inverse probability of treatment weighting to address confounding by indication in comparative effectiveness research of oral anticoagulants. J. Comp. Eff. Res. 9, 603–614 (2020).
Desai, R. J. & Franklin, J. M. Alternative approaches for confounding adjustment in observational studies using weighting based on the propensity score: a primer for practitioners. BMJ 367, l5657 (2019).
Austin, P. C. & Stuart, E. A. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat. Med. 34, 3661–3679 (2015).
Austin, P. C. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar. Behav. Res. 46, 399–424 (2011).
Austin, P. C. A tutorial and case study in propensity score analysis: an application to estimating the effect of in-hospital smoking cessation counseling on mortality. Multivar. Behav. Res. 46, 119–151 (2011).
DeMets, D. L., Psaty, B. M. & Fleming, T. R. When can intermediate outcomes be used as surrogate outcomes. JAMA 323, 1184–1185 (2020).
Prentice, R. L. Surrogate endpoints in clinical trials: definition and operational criteria. Stat. Med. 8, 431–440 (1989).
Weiss, S. L. et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr. Crit. Care Med. 21, e52–e106 (2020).
Usher, M. G. et al. Patient heterogeneity and the J-curve relationship between time-to-antibiotics and the outcomes of patients admitted with bacterial infection. Crit. Care Med. 50, 799–809 (2022).
Lin, J. C. et al. New or progressive multiple organ dysfunction syndrome in pediatric severe sepsis: a sepsis phenotype with higher morbidity and mortality. Pediatr. Crit. Care Med. 18, 8–16 (2017).
Zimmerman, J. J. et al. Critical illness factors associated with long-term mortality and health-related quality of life morbidity following community-acquired pediatric septic shock. Crit. Care Med. 48, 319–328 (2020).
Acknowledgements
We acknowledge Lisa Buckingham at CLARITY/McMaster University for help with building the electronic case report form, Ruxandra Pinto for additional input on data analyses; Cheyenne Matinnia, Arash Khosroawshahi, Matthew Van Huyse (The Hospital for Sick Children), Amy Bartholomew, William Blair (McMaster Children’s Hospital), Afsanah Afshar (BC Children’s Hospital), Dejana Nikitovic, Donovan Duncan, Farhan Zahid (Alberta Children’s Hospital), Amina Hasanova, Mary-Ellen French (CHU Ste. Justine), and Shauna O’Donnell (Montreal Children’s Hospital) for assistance with data collection.
Funding
This work was supported (in part) by the Canadian Society of Hospital Pharmacists Research and Education Foundation. S.P. is supported by a SickKids Clinician-Scientist Training Program Scholarship from The Hospital for Sick Children. The funder/sponsor did not play any role in the study design, conduct, data collection, management, interpretation, manuscript review, or preparation of this work.
Author information
Authors and Affiliations
Contributions
S.P. conceptualized and designed the study, designed the data collection instrument, collected data, carried out the analyses, drafted the initial manuscript and reviewed and revised the manuscript. N.D. and R.A.F. conceptualized and designed the study, designed the data collection instrument, supervised data collection, and critically reviewed the manuscript for important intellectual content. P.F., E.G., J.S.H., P.J., N.M., S.M., J.M.P., A.H.R., M.S., and W.S. designed the data collection instrument and reviewed and revised the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethics approval and consent to participate
All research was performed in accordance with the Declaration of Helsinki and institutional research ethics board approval with waiver for informed consent was obtained at all sites: The Hospital for Sick Children, McMaster Children’s Hospital, BC Children’s Hospital, Alberta Children’s Hospital, CHU Ste Justine and Montreal Children’s Hospital.
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
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Pong, S., Fowler, R.A., Fontela, P. et al. Association of delayed adequate antimicrobial treatment and organ dysfunction in pediatric bloodstream infections. Pediatr Res 95, 705–711 (2024). https://doi.org/10.1038/s41390-023-02836-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41390-023-02836-3
- Springer Nature America, Inc.