Association of Delayed Antimicrobial Therapy with One-Year Mortality in Pediatric Sepsis

Overview

Journal Shock

Date 2017 Jan 24

PMID 28114166

Citations 19

Authors

Moonjoo Han

Julie C Fitzgerald

Fran Balamuth

Luke Keele

Elizabeth R Alpern

Jane Lavelle

Marianne Chilutti

Robert W Grundmeier

Vinay M Nadkarni

Neal J Thomas

Scott L Weiss

Affiliations

Soon will be listed here.

Abstract

Objective: Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis.

Design: Retrospective observational study.

Setting: Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013.

Patients: One hundred sixty patients aged ≤21 years treated for severe sepsis.

Interventions: None.

Measurements And Main Results: We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or >3 h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3 h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3 h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0).

Conclusions: Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.

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References

van Paridon B, Sheppard C, G G, Joffe A . Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care. Crit Care. 2015; 19:293. PMC: 4539944. DOI: 10.1186/s13054-015-1010-x. View

Gaieski D, Mikkelsen M, Band R, Pines J, Massone R, Furia F . Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010; 38(4):1045-53. DOI: 10.1097/CCM.0b013e3181cc4824. View

Garnacho-Montero J, Aldabo-Pallas T, Garnacho-Montero C, Cayuela A, Jimenez R, Barroso S . Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis. Crit Care. 2006; 10(4):R111. PMC: 1751000. DOI: 10.1186/cc4995. View

Zurovsky Y, Barbiro E . Hypovolemia in rats increases mortality rates following endotoxin administration. Exp Toxicol Pathol. 2000; 52(1):37-42. DOI: 10.1016/S0940-2993(00)80013-5. View

Varpula M, Karlsson S, Parviainen I, Ruokonen E, Pettila V . Community-acquired septic shock: early management and outcome in a nationwide study in Finland. Acta Anaesthesiol Scand. 2007; 51(10):1320-6. DOI: 10.1111/j.1399-6576.2007.01439.x. View

Quartin A, Schein R, Kett D, Peduzzi P . Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA. 1997; 277(13):1058-63. View

Prokosch H, Ganslandt T . Perspectives for medical informatics. Reusing the electronic medical record for clinical research. Methods Inf Med. 2009; 48(1):38-44. View

Czaja A, Zimmerman J, Nathens A . Readmission and late mortality after pediatric severe sepsis. Pediatrics. 2009; 123(3):849-57. DOI: 10.1542/peds.2008-0856. View

Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik S . The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med. 1998; 244(5):379-86. DOI: 10.1046/j.1365-2796.1998.00379.x. View

10.

Benjamim C, Hogaboam C, Kunkel S . The chronic consequences of severe sepsis. J Leukoc Biol. 2003; 75(3):408-12. DOI: 10.1189/jlb.0503214. View

11.

Needham D, Davidson J, Cohen H, Hopkins R, Weinert C, Wunsch H . Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med. 2011; 40(2):502-9. DOI: 10.1097/CCM.0b013e318232da75. View

12.

Horan T, Andrus M, Dudeck M . CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008; 36(5):309-32. DOI: 10.1016/j.ajic.2008.03.002. View

13.

Jaramillo-Bustamante J, Marin-Agudelo A, Fernandez-Laverde M, Bareno-Silva J . Epidemiology of sepsis in pediatric intensive care units: first Colombian multicenter study. Pediatr Crit Care Med. 2012; 13(5):501-8. DOI: 10.1097/PCC.0b013e31823c980f. View

14.

Pollack M, Patel K, Ruttimann U . PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med. 1996; 24(5):743-52. DOI: 10.1097/00003246-199605000-00004. View

15.

Thiel S, Asghar M, Micek S, Reichley R, Doherty J, Kollef M . Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis. Crit Care Med. 2009; 37(3):819-24. DOI: 10.1097/CCM.0b013e318196206b. View

16.

Weiss S, Fitzgerald J, Pappachan J, Wheeler D, Jaramillo-Bustamante J, Salloo A . Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015; 191(10):1147-57. PMC: 4451622. DOI: 10.1164/rccm.201412-2323OC. View

17.

Hartman M, Linde-Zwirble W, Angus D, Watson R . Trends in the epidemiology of pediatric severe sepsis*. Pediatr Crit Care Med. 2013; 14(7):686-93. DOI: 10.1097/PCC.0b013e3182917fad. View

18.

Wang T, DerHovanessian A, De Cruz S, Belperio J, Deng J, Soo Hoo G . Subsequent infections in survivors of sepsis: epidemiology and outcomes. J Intensive Care Med. 2013; 29(2):87-95. PMC: 4393330. DOI: 10.1177/0885066612467162. View

19.

Bernard G, Vincent J, Laterre P, LaRosa S, Dhainaut J, Lopez-Rodriguez A . Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001; 344(10):699-709. DOI: 10.1056/NEJM200103083441001. View

20.

Goldstein B, Giroir B, Randolph A . International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005; 6(1):2-8. DOI: 10.1097/01.PCC.0000149131.72248.E6. View