Short URL: openmetaanalysis.github.io/sepsis-antibiotics

View the Project on GitHub (for authors)

Clinical summary: This meta-analysis of patients with severe sepsis or septic shock suggests that the clinical intervention is effective if appropriate antibiotics are administered within 1 hour. The large Kaiser cohort (Liu, 2017), although not able to be pooled due to the method of reporting benefit, also supports this intervention, including in the subgroup of patients with severe sepsis. The heterogeneity in stuides of timing was 'may not be important' (residual I2 = 18%). We included cohort studies of treating patients with severe sepsis or septic shock with adequate antibiotics that reported the benefit of administraton within one hour compared to more than one hour. We exluded studies that did not report the benefit adjusted for severity of illness. Additional interpretations may be in the references in the 'Cited by' section below.

Methods overview: This repository is an openMetaAnalysis that combines methods of scoping, rapid, and living systematic reviews. This analysis updates one or more previously published review(s)(1).

  Newer studies included are listed in the references. Rationale for newer trials excluded may be listed at the end of the references.

A comparison of studies included in this review compared to prior reviews are in the table, reconciliation of studies included with prior meta-analyses. Studies were abstacted into standardized tables of , and results.

Results: Details of the studies included are in the:

Below is the forest plot for the primary outcome. Additional Forest plots may be available. Image of forest plot of primary outcome

References:

Systematic review(s)

Most recent review(s) at time of last revision of this repository

  1. Pepper DJ, Sun J, Cui X, Welsh J, Natanson C, Eichacker PQ. Antibiotic- and Fluid-Focused Bundles Potentially Improve Sepsis Management, but High-Quality Evidence Is Lacking for the Specificity Required in the Centers for Medicare and Medicaid Service's Sepsis Bundle (SEP-1). Crit Care Med. 2019 Jul 31. doi:10.1097/CCM.0000000000003892. PMID: 31369426 Sherwin R, Winters ME, Vilke GM, Wardi G. Does Early and Appropriate Antibiotic Administration Improve Mortality in Emergency Department Patients with Severe Sepsis or Septic Shock? J Emerg Med. 2017 Oct;53(4):588-595. doi: 10.1016/j.jemermed.2016.12.009. Epub 2017 Sep 12. Review. PubMed PMID: 28916120. 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 Sep;43(9):1907-15. doi: 10.1097/CCM.0000000000001142. PMID: 26121073; PMCID: PMC4597314.

Studies

New Studies not included in the most recent review above

  1. Pending

Studies included in the most recent review above

  1. Bloos F, Thomas-Rüddel D, Rüddel H, Engel C, Schwarzkopf D, Marshall JC, Harbarth S, Simon P, Riessen R, Keh D, Dey K, Weiß M, Toussaint S, Schädler D, Weyland A, Ragaller M, Schwarzkopf K, Eiche J, Kuhnle G, Hoyer H, Hartog C, Kaisers U, Reinhart K; MEDUSA Study Group. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study. Crit Care. 2014 Mar 3;18(2):R42. doi:10.1186/cc13755. PMID: 24589043; PMCID: PMC4057316. Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R, Furia FF, Shofer FS, Goyal M. 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 Apr;38(4):1045-53. doi: 10.1097/CCM.0b013e3181cc4824. PMID: 20048677. Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. 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 Aug;42(8):1749-55. doi: 10.1097/CCM.0000000000000330. PMID: 24717459. Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A, Pérez XL, Sirvent JM; Edusepsis Study Group. Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med. 2009 Nov 1;180(9):861-6. doi: 10.1164/rccm.200812-1912OC. PMID: 19696442. Kashiouris MG, Zemore Z, Kimball Z, Stefanou C, Fowler AA 3rd, Fisher B, de Wit M, Pedram S, Sessler CN. Supply Chain Delays in Antimicrobial Administration After the Initial Clinician Order and Mortality in Patients With Sepsis. Crit Care Med. 2019 Jul 24. doi: 10.1097/CCM.0000000000003921. PMID: 31343474. Ko BS, Choi SH, Kang GH, Shin TG, Kim K, Jo YH, Ryoo SM, Kim YJ, Park YS, Kwon WY, Han KS, Choi HS, Chung SP, Suh GJ, Kang H, Lim TH, Kim WY; Korean Shock Society (KoSS) Investigators. Time-to-antibiotics and the outcome of patients with septic shock: A propensity score analysis. Am J Med. 2019 Oct 14. pii: S0002-9343(19)30854-X. doi: 10.1016/j.amjmed.2019.09.012. PMID: 31622578 Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. PMID: 16625125. Peltan ID, Brown SM, Bledsoe JR, Sorensen J, Samore MH, Allen TL, Hough CL. ED Door-to-Antibiotic Time and Long-term Mortality in Sepsis. Chest. 2019 May;155(5):938-946. doi: 10.1016/j.chest.2019.02.008. Epub 2019 Feb 16. PMID: 30779916; PubMed Central PMCID: PMC6533450. Puskarich MA, Trzeciak S, Shapiro NI, Arnold RC, Horton JM, Studnek JR, Kline JA, Jones AE; Emergency Medicine Shock Research Network (EMSHOCKNET). Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med. 2011 Sep;39(9):2066-71. doi: 10.1097/CCM.0b013e31821e87ab. PMID: 21572327; PMCID: PMC3158284. Ryoo SM, Kim WY, Sohn CH, Seo DW, Koh JW, Oh BJ, Lim KS. Prognostic value of timing of antibiotic administration in patients with septic shock treated with early quantitative resuscitation. Am J Med Sci. 2015 Apr;349(4):328-33. doi: 10.1097/MAJ.0000000000000423. PMID: 25651372. Yokota PK, Marra AR, Martino MD, Victor ES, Durão MS, Edmond MB, dos Santos OF. Impact of appropriate antimicrobial therapy for patients with severe sepsis and septic shock--a quality improvement study. PLoS One. 2014 Nov 6;9(11):e104475. doi: 10.1371/journal.pone.0104475. PMID: 25375775; PMCID: PMC4222820.

Studies undergoing review

  1. Pak TR, Young J, McKenna CS, Agan A, DelloStritto L, Filbin MR, Dutta S, Kadri SS, Septimus EJ, Rhee C, Klompas M. Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis. Clin Infect Dis. 2023 Aug 2:ciad450. doi: 10.1093/cid/ciad450. Epub ahead of print. PMID: 37531612. Bulle EB, Peake SL, Finnis M, Bellomo R, Delaney A. Time to antimicrobial therapy in septic shock patients treated with an early goal-directed resuscitation protocol: A post-hoc analysis of the ARISE trial. Emergency Medicine Australasia [Internet]. 2021 [cited 2021 Sep 17];33(3):409–417. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/1742-6723.13634 Taylor SP, Anderson WE, Beam K, Taylor B, Ellerman J, Kowalkowski MA. The Association Between Antibiotic Delay Intervals and Hospital Mortality Among Patients Treated in the Emergency Department for Suspected Sepsis. Crit Care Med. 2021 May 1;49(5):741-747. doi: 10.1097/CCM.0000000000004863. PMID: 33591002. Asner SA, Desgranges F, Schrijver IT, Calandra T. Impact of the timeliness of antibiotic therapy on the outcome of patients with sepsis and septic shock. J Infect. 2021 Mar 17:S0163-4453(21)00116-X. doi: 10.1016/j.jinf.2021.03.003. Epub ahead of print. PMID: 33722641. Kalil AC, Johnson DW, Lisco SJ, Sun J. Early Goal-Directed Therapy for Sepsis: A Novel Solution for Discordant Survival Outcomes in Clinical Trials. Crit Care Med. 2017 Apr;45(4):607-614. doi: 10.1097/CCM.0000000000002235. PMID: 28067711. Fahel BVB, Manciola M, Lima G, Barbosa MH, Starteri C, Ramos JGR, Caldas JR, Passos RDH. There is no association between weekend admissions and delays in antibiotic administration for patients admitted to the emergency department with suspicion of sepsis: A retrospective cohort study. Medicine (Baltimore). 2020 Nov 20;99(47):e23256. doi: 10.1097/MD.0000000000023256. PMID: 33217847; PMCID: PMC7676526. Alam N, Oskam E, Stassen PM, Exter PV, van de Ven PM, Haak HR, Holleman F, Zanten AV, Leeuwen-Nguyen HV, Bon V, Duineveld BAM, Nannan Panday RS, Kramer MHH, Nanayakkara PWB; PHANTASi Trial Investigators and the ORCA (Onderzoeks Consortium Acute Geneeskunde) Research Consortium the Netherlands. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018 Jan;6(1):40-50. doi: 10.1016/S2213-2600(17)30469-1. Epub 2017 Nov 28. PMID: 29196046. *Not all patients received appropriate antibiotics.* Castaño P, Plaza M, Molina F, Hincapié C, Maya W, Cataño J, González J, León A, Jaimes F. Antimicrobial agent prescription: a prospective cohort study in patients with sepsis and septic shock. Trop Med Int Health. 2019 Feb;24(2):175-184. doi: 10.1111/tmi.13186. Epub 2018 Dec 13. PMID: 30489005. (included by Rothrock) Bulle, EB et al. Time to antimicrobial therapy in septic shock patients treated with an early goal‐directed resuscitation protocol: A post‐hoc analysis of the ARISE trial. Emergency Medicine Australasia. 2020. doi:10.1111/1742-6723.13634. ISSN 1742-6731. *Not all patients received appropriate antibiotics.* Rothrock, SG et al. Outcome of Immediate Versus Early Antibiotics in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis, Annals of Emergency Medicine, 2020 DOI: 10.1016/j.annemergmed.2020.04.042. Parish B, Cooksley T, Haji-Michael P. Effectiveness of early antibiotic administration in septic patients with cancer. Acute Med. 2013;12(4):196-200. PMID: 24364049. Corl KA, Zeba F, Caffrey AR, Hermenau M, Lopes V, Phillips G, Merchant RC, Levy MM, LaPlante KL. Delay in Antibiotic Administration Is Associated With Mortality Among Septic Shock Patients With Staphylococcus aureus Bacteremia. Crit Care Med. 2020 Apr;48(4):525-532. doi: 10.1097/CCM.0000000000004212. PMID: 32205599. Bautista Hernández A, de Vega-Ríos E, Serrano Ballesteros J, Useros Braña D, Cardeñoso Domingo L, Figuerola Tejerina A, Jiménez Jiménez D, de Los Santos Gil I, Sáez Béjar C. Impact of the implementation of a Sepsis Code Program in medical patient management: a cohort study in an Internal Medicine ward. Rev Esp Quimioter. 2022 Jan 31:bautista31jan2022. doi: 10.37201/req/132.2021. Epub ahead of print. PMID: 35099161.

Studies excluded - selected list of important studies
  1. Abe T, Kushimoto S, Tokuda Y, Phillips GS, Rhodes A, Sugiyama T, Komori A, Iriyama H, Ogura H, Fujishima S, Shiraishi A, Saitoh D, Mayumi T, Naito T, Takuma K, Nakada TA, Shiino Y, Tarui T, Hifumi T, Otomo Y, Okamoto K, Umemura Y, Kotani J, Sakamoto Y, Sasaki J, Shiraishi SI, Tsuruta R, Hagiwara A, Yamakawa K, Masuno T, Takeyama N, Yamashita N, Ikeda H, Ueyama M, Gando S; JAAM FORECAST group. Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study. Crit Care. 2019 Nov 19;23(1):360. doi: 10.1186/s13054-019-2644-x. PMID: 31744549. Time 0 was recognition of sepsis and not patient arrival. No data on the appropriateness of antibiotic choices. Baghdadi JD, Brook RH, Uslan DZ, Needleman J, Bell DS, Cunningham WE, Wong MD. Association of a Care Bundle for Early Sepsis Management With Mortality Among Patients With Hospital-Onset or Community-Onset Sepsis. JAMA Intern Med. 2020 Apr 6;180(5):707–16. doi: 10.1001/jamainternmed.2020.0183. Epub ahead of print. PMID: 32250412; PMCID: PMC7136852. Results are not reported based on receipt of antibiotics within one hour. Filbin MR, Thorsen JE, Zachary TM, Lynch JC, Matsushima M, Belsky JB, Heldt T, Reisner AT. Antibiotic Delays and Feasibility of a 1-Hour-From-Triage Antibiotic Requirement: Analysis of an Emergency Department Sepsis Quality Improvement Database. Ann Emerg Med. 2019 Sep 24. pii: S0196-0644(19)30593-1. doi: 10.1016/j.annemergmed.2019.07.017. PMID: 31561998. Results are not reported based on receipt of antibiotics within one hour. Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The Timing of Early Antibiotics and Hospital Mortality in Sepsis. Am J Respir Crit Care Med. 2017 Oct 1;196(7):856-863. doi:10.1164/rccm.201609-1848OC. PMID: 28345952. Results are available based on administration at 3 hours, but not at one hour. However, has plot of adjusted odds ratios of mortality based on timing of antibiotics. This plot supports antibiotics within one hour. Peltan ID, Mitchell KH, Rudd KE, Mann BA, Carlbom DJ, Hough CL, Rea TD, Brown SM. Physician Variation in Time to Antimicrobial Treatment for Septic Patients Presenting to the Emergency Department. Crit Care Med. 2017 Jun;45(6):1011-1018. doi: 10.1097/CCM.0000000000002436. PMID: 28426466 Results are not available at one hour. However, adjusted odds ratios of mortality based on timing of antibiotics supports antibiotics within one hour. Pruinelli L, Westra BL, Yadav P, Hoff A, Steinbach M, Kumar V, Delaney CW, Simon G. Delay Within the 3-Hour Surviving Sepsis Campaign Guideline on Mortality for Patients With Severe Sepsis and Septic Shock. Crit Care Med. 2018 Apr;46(4):500-505. doi: 10.1097/CCM.0000000000002949. PMID: 29298189; PMCID: PMC5851815. Results are not available at one hour. However, adjusted odds ratios of mortality based on timing of antibiotics supports antibiotics within one hour. Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, Lemeshow S, Osborn T, Terry KM, Levy MM. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med. 2017 Jun 8;376(23):2235-2244. doi: 10.1056/NEJMoa1703058. PMID: 28528569; PMCID: PMC5538258 Results are available based on administration at 3 hours, but not at one hour Whiles BB, Deis AS, Simpson SQ. Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients. Crit Care Med. 2017 Apr;45(4):623-629. doi: 10.1097/CCM.0000000000002262. PMID: 28169944; PMCID: PMC5374449. Does not report the benefit of less than one hour versus longer.

Funding for this review

  1. None.

Cited by

This repository is cited by:

  1. WikiDoc contributors. Pending. WikiDoc. Fef 24, 2015. Available at: http://www.wikidoc.org/index.php/Pending. Accessed February 24, 2015.