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Critical Care
Published in: Critical Care 2/2014

Open Access 01-04-2014 | Research

Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study

Authors: Frank Bloos, Daniel Thomas-Rüddel, Hendrik Rüddel, Christoph Engel, Daniel Schwarzkopf, John C Marshall, Stephan Harbarth, Philipp Simon, Reimer Riessen, Didier Keh, Karin Dey, Manfred Weiß, Susanne Toussaint, Dirk Schädler, Andreas Weyland, Maximillian Ragaller, Konrad Schwarzkopf, Jürgen Eiche, Gerhard Kuhnle, Heike Hoyer, Christiane Hartog, Udo Kaisers, Konrad Reinhart, for the MEDUSA Study Group

Published in: Critical Care | Issue 2/2014

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Abstract

Introduction

Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome.

Methods

In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality.

Results

Median time to AT was 2.1 (IQR 0.8 – 6.0) hours and 3 hours (-0.1 – 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001).

Conclusions

A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.
Appendix
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Literature
1.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013, 41: 580-637. 10.1097/CCM.0b013e31827e83afCrossRefPubMed
2.
Larche J, Azoulay E, Fieux F, Mesnard L, Moreau D, Thiery G, Darmon M, Le Gall JR, Schlemmer B: Improved survival of critically ill cancer patients with septic shock. Intensive Care Med 2003, 29: 1688-1695. 10.1007/s00134-003-1957-yCrossRefPubMed
3.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, 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, 34: 1589-1596. 10.1097/01.CCM.0000217961.75225.E9CrossRefPubMed
4.
Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC: The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010, 38: 367-374. 10.1097/CCM.0b013e3181cb0cdcCrossRefPubMed
5.
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, 38: 1045-1053. 10.1097/CCM.0b013e3181cc4824CrossRefPubMed
6.
Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A, Perez XL, Sirvent JM: Effectiveness of treatments for severe sepsis: a prospective multicenter observational study. Am J Respir Crit Care Med 2009, 180: 861-866. 10.1164/rccm.200812-1912OCCrossRefPubMed
7.
Boyer A, Vargas F, Coste F, Saubusse E, Castaing Y, Gbikpi-Benissan G, Hilbert G, Gruson D: Influence of surgical treatment timing on mortality from necrotizing soft tissue infections requiring intensive care management. Intensive Care Med 2009, 35: 847-853. 10.1007/s00134-008-1373-4CrossRefPubMed
8.
Moss RL, Musemeche CA, Kosloske AM: Necrotizing fasciitis in children: prompt recognition and aggressive therapy improve survival. J Pediatr Surg 1996, 31: 1142-1146. 10.1016/S0022-3468(96)90104-9CrossRefPubMed
9.
Buck DL, Vester-Andersen M, Moller MH, Danish Clinical Register of Emergency S: Surgical delay is a critical determinant of survival in perforated peptic ulcer. Br J Surg 2013, 100: 1045-1049. 10.1002/bjs.9175CrossRefPubMed
10.
Marshall JC, Maier RV, Jimenez M, Dellinger EP: Source control in the management of severe sepsis and septic shock: an evidence-based review. Crit Care Med 2004, 32: S513-S526. 10.1097/01.CCM.0000143119.41916.5DCrossRefPubMed
11.
Cardoso T, Carneiro AH, Ribeiro O, Teixeira-Pinto A, Costa-Pereira A: Reducing mortality in severe sepsis with the implementation of a core 6-hour bundle: results from the Portuguese community-acquired sepsis study (SACiUCI study). Crit Care 2010, 14: R83. 10.1186/cc9008PubMedCentralCrossRefPubMed
12.
Castellanos-Ortega A, Suberviola B, Garcia-Astudillo LA, Holanda MS, Ortiz F, Llorca J, Delgado-Rodriguez M: Impact of the surviving sepsis campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study. Crit Care Med 2010, 38: 1036-1043. 10.1097/CCM.0b013e3181d455b6CrossRefPubMed
13.
Ferrer R, Artigas A, Levy MM, Blanco J, Gonzalez-Diaz G, Garnacho-Montero J, Ibanez J, Palencia E, Quintana M, de la Torre-Prados MV: Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 2008, 299: 2294-2303. 10.1001/jama.299.19.2294CrossRefPubMed
14.
Chamberlain DJ, Willis EM, Bersten AB: The severe sepsis bundles as processes of care: a meta-analysis. Aust Crit Care 2011, 24: 229-243. 10.1016/j.aucc.2011.01.003CrossRefPubMed
15.
Barochia AV, Cui X, Vitberg D, Suffredini AF, O'Grady NP, Banks SM, Minneci P, Kern SJ, Danner RL, Natanson C, Eichacker PQ: Bundled care for septic shock: an analysis of clinical trials. Crit Care Med 2010, 38: 668-678. 10.1097/CCM.0b013e3181cb0ddfPubMedCentralCrossRefPubMed
16.
Brunkhorst FM, Engel C, Ragaller M, Welte T, Rossaint R, Gerlach H, Mayer K, John S, Stuber F, Weiler N, Oppert M, Moerer O, Bogatsch H, Reinhart K, Loeffler M, Hartog C: Practice and perception – a nationwide survey of therapy habits in sepsis. Crit Care Med 2008, 36: 2719-2725. 10.1097/CCM.0b013e318186b6f3CrossRefPubMed
17.
Hranjec T, Rosenberger LH, Swenson B, Metzger R, Flohr TR, Politano AD, Riccio LM, Popovsky KA, Sawyer RG: 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: 774-780. 10.1016/S1473-3099(12)70151-2PubMedCentralCrossRefPubMed
18.
Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, Gomersall CD, Faruq MO, Shrestha BR, Gia Binh N, Arabi YM, Salahuddin N, Wahyuprajitno B, Tu ML, Wahab AY, Hameed AA, Nishimura M, Procyshyn M, Chan YH: Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. Br Med J 2011, 342: d3245. 10.1136/bmj.d3245CrossRef
19.
Hitti EA, Lewin JJ 3rd, Lopez J, Hansen J, Pipkin M, Itani T, Gurny P: Improving door-to-antibiotic time in severely septic emergency department patients. J Emerg Med 2012, 42: 462-469. 10.1016/j.jemermed.2011.05.015CrossRefPubMed
20.
Puskarich MA, Trzeciak S, Shapiro NI, Arnold RC, Horton JM, Studnek JR, Kline JA, Jones AE: Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med 2011, 39: 2066-2071. 10.1097/CCM.0b013e31821e87abPubMedCentralCrossRefPubMed
21.
Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K: Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358: 125-139. 10.1056/NEJMoa070716CrossRefPubMed
22.
Vogel F, Bodmann KF, Expert Committee of the Paul-Ehrlich-Gesellschaft: [Recommendations about the calculated parenteral initial therapy of bacterial diseases in adults]. Chemother J 2004, 13: 46-105.
23.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart K, Suter PM, Thijs LG: The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the european society of intensive care medicine. Intensive Care Med 1996, 22: 707-710. 10.1007/BF01709751CrossRefPubMed
24.
Le Gall JR, Lemeshow S, Saulnier F: A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 270: 2957-2963. 10.1001/jama.1993.03510240069035CrossRefPubMed
25.
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/01.CCM.0000298158.12101.41CrossRefPubMed
26.
Mulier S, Penninckx F, Verwaest C, Filez L, Aerts R, Fieuws S, Lauwers P: Factors affecting mortality in generalized postoperative peritonitis: multivariate analysis in 96 patients. World J Surg 2003, 27: 379-384. 10.1007/s00268-002-6705-xCrossRefPubMed
27.
Torer N, Yorganci K, Elker D, Sayek I: Prognostic factors of the mortality of postoperative intraabdominal infections. Infection 2010, 38: 255-260. 10.1007/s15010-010-0021-4CrossRefPubMed
28.
Tridente A, Clarke GM, Walden A, McKechnie S, Hutton P, Mills GH, Gordon AC, Holloway PA, Chiche JD, Bion J, Stuber F, Garrard C, Hinds CJ, Gen OI: Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort. Intensive Care Med 2014, 40: 202-210. 10.1007/s00134-013-3158-7CrossRefPubMed
29.
Labelle A, Juang P, Reichley R, Micek S, Hoffmann J, Hoban A, Hampton N, Kollef M: The determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment. Crit Care Med 2012, 40: 2016. 2021 10.1097/CCM.0b013e318250aa72CrossRefPubMed
30.
Francis M, Rich T, Williamson T, Peterson D: Effect of an emergency department sepsis protocol on time to antibiotics in severe sepsis. CJEM 2010, 12: 303-310.PubMed
31.
Shapiro NI, Howell MD, Talmor D, Lahey D, Ngo L, Buras J, Wolfe RE, Weiss JW, Lisbon A: Implementation and outcomes of the multiple urgent sepsis therapies (MUST) protocol. Crit Care Med 2006, 34: 1025-1032. 10.1097/01.CCM.0000206104.18647.A8CrossRefPubMed
32.
Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH: Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002, 122: 262-268. 10.1378/chest.122.1.262CrossRefPubMed
33.
Meehan TP, Fine MJ, Krumholz HM, Scinto JD, Galusha DH, Mockalis JT, Weber GF, Petrillo MK, Houck PM, Fine JM: Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 1997, 278: 2080. 2084 10.1001/jama.1997.03550230056037CrossRefPubMed
34.
Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P, Guzman J, Marshall J, Parrillo JE, Skrobik Y, Kumar A, Cooperative Antimicrobial Therapy of Septic Shock Database Research Group: Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med 2009, 35: 871-881. 10.1007/s00134-008-1367-2CrossRefPubMed
35.
Garnacho-Montero J, Aldabo-Pallas T, Garnacho-Montero C, Cayuela A, Jimenez R, Barroso S, Ortiz-Leyba C: 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: R111. 10.1186/cc4995PubMedCentralCrossRefPubMed
36.
Barie PS, Hydo LJ, Shou J, Larone DH, Eachempati SR: Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection. Surg Infect (Larchmt) 2005, 6: 41-54. 10.1089/sur.2005.6.41CrossRef
37.
Noble DW, Gould IM: Antibiotics for surgical patients: the faster the better? Lancet Infect Dis 2012, 12: 741-742. 10.1016/S1473-3099(12)70208-6CrossRefPubMed
38.
Harbarth S, Garbino J, Pugin J, Romand JA, Lew D, Pittet D: Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med 2003, 115: 529-535. 10.1016/j.amjmed.2003.07.005CrossRefPubMed
39.
Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Simon D, Peters C, Ahsan M, Chateau D: Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009, 136: 1237-1248.PubMed
40.
Abah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi de Carvalho F, Paiva JA, Cakar N, Ma X, Eggimann P, Antonelli M, Bonten MJ, Csomos A, Krueger WA, Mikstacki A, Lipman J, Depuydt P, Vesin A, Garrouste-Orgeas M, Zahar JR, Blot S, Carlet J, Brun-Buisson C, Martin C, Rello J, Dimopoulos G, Timsit JF: Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med 2012, 38: 1930. 1945 10.1007/s00134-012-2695-9CrossRef
Metadata
Title
Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study
Authors
Frank Bloos
Daniel Thomas-Rüddel
Hendrik Rüddel
Christoph Engel
Daniel Schwarzkopf
John C Marshall
Stephan Harbarth
Philipp Simon
Reimer Riessen
Didier Keh
Karin Dey
Manfred Weiß
Susanne Toussaint
Dirk Schädler
Andreas Weyland
Maximillian Ragaller
Konrad Schwarzkopf
Jürgen Eiche
Gerhard Kuhnle
Heike Hoyer
Christiane Hartog
Udo Kaisers
Konrad Reinhart
for the MEDUSA Study Group
Publication date
01-04-2014
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2014
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc13755

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