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Published in: Critical Care 1/2019

Open Access 01-12-2019 | Septicemia | Research

Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study

Authors: Toshikazu Abe, Shigeki Kushimoto, Yasuharu Tokuda, Gary S. Phillips, Andrew Rhodes, Takehiro Sugiyama, Akira Komori, Hiroki Iriyama, Hiroshi Ogura, Seitaro Fujishima, Atsushi Shiraishi, Daizoh Saitoh, Toshihiko Mayumi, Toshio Naito, Kiyotsugu Takuma, Taka-aki Nakada, Yasukazu Shiino, Takehiko Tarui, Toru Hifumi, Yasuhiro Otomo, Kohji Okamoto, Yutaka Umemura, Joji Kotani, Yuichiro Sakamoto, Junichi Sasaki, Shin-ichiro Shiraishi, Ryosuke Tsuruta, Akiyoshi Hagiwara, Kazuma Yamakawa, Tomohiko Masuno, Naoshi Takeyama, Norio Yamashita, Hiroto Ikeda, Masashi Ueyama, Satoshi Gando, on behalf of JAAM FORECAST group

Published in: Critical Care | Issue 1/2019

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Abstract

Background

Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan.

Methods

This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0–60, 61–120, 121–180, 181–240, 241–360, and 361–1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with “hospital” as the grouping variable.

Results

Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55–189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48–164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39–180 min)] and longest in patients transferred from wards [120 min (62–226)]. Overall crude mortality was 23.4%, where patients in the 0–60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3–34.1%)], whereas those in the 61–120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5–26.6%)]. Differences in mortality were noted only between the 0–60 min and 61–120 min groups.

Conclusions

We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.
Literature
1.
go back to reference Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–73.CrossRef Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–73.CrossRef
2.
go back to reference Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med. 2008;36:296–327.CrossRef Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med. 2008;36:296–327.CrossRef
3.
go back to reference Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med. 2013;41:580–637.CrossRef Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med. 2013;41:580–637.CrossRef
4.
go back to reference Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock. Intensive Care Med. 2017;43:304–77.CrossRef Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock. Intensive Care Med. 2017;43:304–77.CrossRef
5.
go back to reference Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign bundle: 2018 update. Intensive Care Med. 2018;46:997–1000. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign bundle: 2018 update. Intensive Care Med. 2018;46:997–1000.
6.
go back to reference Spiegel R, Farkas JD, Rola P, Kenny JE, Olusanya S, Marik PE, et al. The 2018 Surviving Sepsis Campaign’s treatment bundle: when guidelines outpace the evidence supporting their use. Ann Emerg Med. 2019;73:356–8.CrossRef Spiegel R, Farkas JD, Rola P, Kenny JE, Olusanya S, Marik PE, et al. The 2018 Surviving Sepsis Campaign’s treatment bundle: when guidelines outpace the evidence supporting their use. Ann Emerg Med. 2019;73:356–8.CrossRef
7.
go back to reference Alam N, Oskam E, Stassen PM, Exter PV, van de Ven PM, Haak HR, et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018;6:40–50.CrossRef Alam N, Oskam E, Stassen PM, Exter PV, van de Ven PM, Haak HR, et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018;6:40–50.CrossRef
8.
go back to reference Abe T, Ogura H, Shiraishi A, Kushimoto S, Saitoh D, Fujishima S, et al. Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: the FORECAST study. Crit Care. 2018;22:322.CrossRef Abe T, Ogura H, Shiraishi A, Kushimoto S, Saitoh D, Fujishima S, et al. Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: the FORECAST study. Crit Care. 2018;22:322.CrossRef
9.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–6.CrossRef Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–6.CrossRef
10.
go back to reference Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235–44.CrossRef Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376:2235–44.CrossRef
11.
go back to reference Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017;196:856–63.CrossRef Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017;196:856–63.CrossRef
12.
go back to reference Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42:1749–55.CrossRef Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42:1749–55.CrossRef
13.
go back to reference Evans IVR, Phillips GS, Alpern ER, Angus DC, Friedrich ME, Kissoon N, et al. Association between the New York sepsis care mandate and in-hospital mortality for pediatric sepsis. JAMA. 2018;320:358–67.CrossRef Evans IVR, Phillips GS, Alpern ER, Angus DC, Friedrich ME, Kissoon N, et al. Association between the New York sepsis care mandate and in-hospital mortality for pediatric sepsis. JAMA. 2018;320:358–67.CrossRef
14.
go back to reference Peltan ID, Brown SM, Bledsoe JR, Sorensen J, Samore MH, Allen TL, et al. ED door-to-antibiotic time and long-term mortality in sepsis. Chest. 2019;155:938–46.CrossRef Peltan ID, Brown SM, Bledsoe JR, Sorensen J, Samore MH, Allen TL, et al. ED door-to-antibiotic time and long-term mortality in sepsis. Chest. 2019;155:938–46.CrossRef
15.
go back to reference Sterling SA, Miller WR, Pryor J, Puskarich MA, Jones AE. The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. Crit Care Med. 2015;43:1907–15.CrossRef Sterling SA, Miller WR, Pryor J, Puskarich MA, Jones AE. The impact of timing of antibiotics on outcomes in severe sepsis and septic shock: a systematic review and meta-analysis. Crit Care Med. 2015;43:1907–15.CrossRef
16.
go back to reference Filbin MR, Lynch J, Gillingham TD, Thorsen JE, Pasakarnis CL, Nepal S, et al. Presenting symptoms independently predict mortality in septic shock: importance of a previously unmeasured confounder. Crit Care Med. 2018;46:1592–9.CrossRef Filbin MR, Lynch J, Gillingham TD, Thorsen JE, Pasakarnis CL, Nepal S, et al. Presenting symptoms independently predict mortality in septic shock: importance of a previously unmeasured confounder. Crit Care Med. 2018;46:1592–9.CrossRef
17.
go back to reference Klompas M, Calandra T, Singer M. Antibiotics for sepsis-finding the equilibrium. JAMA. 2018;320:1433–4.CrossRef Klompas M, Calandra T, Singer M. Antibiotics for sepsis-finding the equilibrium. JAMA. 2018;320:1433–4.CrossRef
18.
go back to reference Faine BA, Noack JM, Wong T, Messerly JT, Ahmed A, Fuller BM, et al. Interhospital transfer delays appropriate treatment for patients with severe sepsis and septic shock: a retrospective cohort study. Crit Care Med. 2015;43:2589–96.CrossRef Faine BA, Noack JM, Wong T, Messerly JT, Ahmed A, Fuller BM, et al. Interhospital transfer delays appropriate treatment for patients with severe sepsis and septic shock: a retrospective cohort study. Crit Care Med. 2015;43:2589–96.CrossRef
19.
go back to reference Abe T, Ogura H, Kushimoto S, Shiraishi A, Sugiyama T, Deshpande GA, et al. Variations in infection sites and mortality rates among patients in intensive care units with severe sepsis and septic shock in Japan. J Intensive Care. 2019;7:28.CrossRef Abe T, Ogura H, Kushimoto S, Shiraishi A, Sugiyama T, Deshpande GA, et al. Variations in infection sites and mortality rates among patients in intensive care units with severe sepsis and septic shock in Japan. J Intensive Care. 2019;7:28.CrossRef
20.
go back to reference Barochia AV, Cui X, Vitberg D, Suffredini AF, O’Grady NP, Banks SM, et al. Bundled care for septic shock: an analysis of clinical trials. Crit Care Med. 2010;38:668–78.CrossRef Barochia AV, Cui X, Vitberg D, Suffredini AF, O’Grady NP, Banks SM, et al. Bundled care for septic shock: an analysis of clinical trials. Crit Care Med. 2010;38:668–78.CrossRef
21.
go back to reference Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. JAMA. 2017;318:1233–40.CrossRef Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. JAMA. 2017;318:1233–40.CrossRef
22.
go back to reference Deis AS, Whiles BB, Brown AR, Satterwhite CL, Simpson SQ. Three-hour bundle compliance and outcomes in patients with undiagnosed severe sepsis. Chest. 2018;153:39–45.CrossRef Deis AS, Whiles BB, Brown AR, Satterwhite CL, Simpson SQ. Three-hour bundle compliance and outcomes in patients with undiagnosed severe sepsis. Chest. 2018;153:39–45.CrossRef
23.
go back to reference Fujishima S, Gando S, Saitoh D, Mayumi T, Kushimoto S, Shiraishi S, et al. A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines. J Infect Chemother. 2014;20:115–20.CrossRef Fujishima S, Gando S, Saitoh D, Mayumi T, Kushimoto S, Shiraishi S, et al. A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines. J Infect Chemother. 2014;20:115–20.CrossRef
24.
go back to reference Pro CI, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–93.CrossRef Pro CI, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–93.CrossRef
25.
go back to reference Investigators A, Group ACT, Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–506.CrossRef Investigators A, Group ACT, Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–506.CrossRef
26.
go back to reference Hranjec T, Rosenberger LH, Swenson B, Metzger R, Flohr TR, Politano AD, et al. Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study. Lancet Infect Dis. 2012;12:774–80.CrossRef Hranjec T, Rosenberger LH, Swenson B, Metzger R, Flohr TR, Politano AD, et al. Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study. Lancet Infect Dis. 2012;12:774–80.CrossRef
27.
go back to reference Webb BJ, Sorensen J, Jephson A, Mecham I, Dean NC. Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study. Eur Respir J. 2019;54:1900057.CrossRef Webb BJ, Sorensen J, Jephson A, Mecham I, Dean NC. Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study. Eur Respir J. 2019;54:1900057.CrossRef
28.
go back to reference Abe T, Tokuda Y, Shiraishi A, Fujishima S, Mayumi T, Sugiyama T, et al. In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission. Crit Care. 2019;23:202.CrossRef Abe T, Tokuda Y, Shiraishi A, Fujishima S, Mayumi T, Sugiyama T, et al. In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission. Crit Care. 2019;23:202.CrossRef
Metadata
Title
Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study
Authors
Toshikazu Abe
Shigeki Kushimoto
Yasuharu Tokuda
Gary S. Phillips
Andrew Rhodes
Takehiro Sugiyama
Akira Komori
Hiroki Iriyama
Hiroshi Ogura
Seitaro Fujishima
Atsushi Shiraishi
Daizoh Saitoh
Toshihiko Mayumi
Toshio Naito
Kiyotsugu Takuma
Taka-aki Nakada
Yasukazu Shiino
Takehiko Tarui
Toru Hifumi
Yasuhiro Otomo
Kohji Okamoto
Yutaka Umemura
Joji Kotani
Yuichiro Sakamoto
Junichi Sasaki
Shin-ichiro Shiraishi
Ryosuke Tsuruta
Akiyoshi Hagiwara
Kazuma Yamakawa
Tomohiko Masuno
Naoshi Takeyama
Norio Yamashita
Hiroto Ikeda
Masashi Ueyama
Satoshi Gando
on behalf of JAAM FORECAST group
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2644-x

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