Optimal antimicrobial therapy and antimicrobial stewardship in sepsis and septic shock
Article information
J Korean Med Assoc. 2019;62(12):638-644
Publication date (electronic) : 2019 December 12
doi :
https://doi.org/10.5124/jkma.2019.62.12.638
Received 2019 October 30; Accepted 2019 November 03.
Abstract
The management of sepsis and septic shock remains challenging. The aim is to apply the optimal antimicrobial therapy and antimicrobial stewardship to patients in state of sepsis or septic shock. To reduce the mortality of sepsis and septic shock, it is critical to promptly administer the appropriate antibiotics with an accurate diagnosis. De-escalation is needed 48 to 72 hours after the first administration of antibiotics depending on the findings of causative pathogens. In the case of antibiotic resistance, the importance of an antibiotic stewardship program is increasingly being emphasized. Antimicrobial stewardship implies coordinated interventions designed to improve the appropriate use of antibiotics by promoting the selection of an optimal drug regimen such as dosing, duration of therapy, and route of administration. An antibiotic stewardship program may also be applied to patients of both sepsis and septic shock. Efforts such as the selection of appropriate empirical antibiotics, de-escalation, and determination of whether to stop antibiotics with procalcitonin may improve the clinical prognosis of patients with sepsis as well as the successful implementation of an antibiotic stewardship program.
Keywords: Sepsis; Septic shock; Anti-infective agents; Anti-bacterial agents; Antibiotic stewardship
Notes
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
References
1. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864–874.
2. Kim J, Kim K, Lee H, Ahn S. Epidemiology of sepsis in Korea: a population-based study of incidence, mortality, cost and risk factors for death in sepsis. Clin Exp Emerg Med 2019;6:49–63.
3. Vincent JL, Marshall JC, Namendys-Silva SA, Francois B, Martin-Loeches I, Lipman J, Reinhart K, Antonelli M, Pickkers P, Njimi H, Jimenez E, Sakr Y. ICON investigators. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respir Med 2014;2:380–386.
4. Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaga-nos T, Schlattmann P, Angus DC, Reinhart K. International Forum of Acute Care Trialists. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 2016;193:259–272.
5. Jeon K, Na SJ, Oh DK, Park S, Choi EY, Kim SC, Seong GM, Heo J, Chang Y, Kwack WG, Kang BJ, Choi WI, Kim KC, Park SY, Kwak SH, Shin YM, Lee HB, Park SH, Cho JH, Kim B, Lim CM. Korean Sepsis Alliance (KSA) study group. Characteristics, management and clinical outcomes of patients with sepsis: a multicenter cohort study in Korea. Acute Crit Care 2019;34:179–191.
6. Shin TG, Hwang SY, Kang GH, Kim WY, Ryoo SM, Kim K, Jo YH, Chung SP, Joo YS, Beom JH, Choi SH, Yoon YH, Kwon WY, Lim TH, Han KS, Choi HS, Suh GJ. Korean Shock Society septic shock registry: a preliminary report. Clin Exp Emerg Med 2017;4:146–153.
7. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315:801–810.
8. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43:304–377.
9. Jeon JH, Park DW. Controversies regarding the new definition of sepsis. Korean J Med 2017;92:342–348.
10. 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;376:2235–2244.
11. 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;43:1907–1915.
12. Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999;115:462–474.
13. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of blood-stream infections on patient outcomes in the ICU setting. Chest 2000;118:146–155.
14. Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Kumar A, Simon D, Peters C, Ahsan M, Chateau D. Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009;136:1237–1248.
15. Micek ST, Roubinian N, Heuring T, Bode M, Williams J, Harrison C, Murphy T, Prentice D, Ruoff BE, Kollef MH. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med 2006;34:2707–2713.
16. 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;34:1589–1596.
17. Zhang D, Micek ST, Kollef MH. Time to appropriate antibiotic therapy is an independent determinant of postinfection ICU and hospital lengths of stay in patients with sepsis. Crit Care Med 2015;43:2133–2140.
18. 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 (CATSS) Database Research Group. CATSS) Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypo-tension prior to initiation of antimicrobial therapy. Intensive Care Med 2009;35:871–881.
19. Iscimen R, Cartin-Ceba R, Yilmaz M, Khan H, Hubmayr RD, Afessa B, Gajic O. Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study. Crit Care Med 2008;36:1518–1522.
20. Puskarich MA, Trzeciak S, Shapiro NI, Arnold RC, Horton JM, Studnek JR, Kline JA, Jones AE. Emergency Medicine Shock Research Network (EMSHOCKNET). EMSHOCKNET). Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resu-scitation protocol. Crit Care Med 2011;39:2066–2071.
21. 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;349:328–333.
22. Burnham JP, Lane MA, Kollef MH. Impact of sepsis classi-fication and multidrug-resistance status on outcome among patients treated with appropriate therapy. Crit Care Med 2015;43:1580–1586.
23. Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, Laporta D, Lapinsky S, Ellis P, Mirzanejad Y, Martinka G, Keenan S, Wood G, Arabi Y, Feinstein D, Kumar A, Dodek P, Kravetsky L, Doucette S. Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med 2010;38:1773–1785.
24. Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis 2004;4:519–527.
25. Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 2014;CD003344.
26. Masterton RG. Antibiotic de-escalation. Crit Care Clin 2011;27:149–162.
27. Wang A, Daneman N, Tan C, Brownstein JS, MacFadden DR. Evaluating the relationship between hospital antibiotic use and antibiotic resistance in common nosocomial pathogens. Infect Control Hosp Epidemiol 2017;38:1457–1463.
28. Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP, Huskins WC, Paterson DL, Fishman NO, Carpenter CF, Brennan PJ, Billeter M, Hooton TM. Infectious Diseases Society of America. Society for Healthcare Epidemiology of America. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44:159–177.
29. Kollef MH, Micek ST. Strategies to prevent antimicrobial resistance in the intensive care unit. Crit Care Med 2005;33:1845–1853.
30. Shorr AF. Review of studies of the impact on Gram-negative bacterial resistance on outcomes in the intensive care unit. Crit Care Med 2009;37:1463–1469.
31. Pollack LA, van Santen KL, Weiner LM, Dudeck MA, Edwards JR, Srinivasan A. Antibiotic stewardship programs in U.S. acute care hospitals: findings from the 2014 National Healthcare Safety Network Annual Hospital Survey. Clin Infect Dis 2016;63:443–449.
32. Silva BN, Andriolo RB, Atallah AN, Salomao R. De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev 2013;CD007934.
33. Rello J, Vidaur L, Sandiumenge A, Rodriguez A, Gualis B, Boque C, Diaz E. De-escalation therapy in ventilator-asso-ciated pneumonia. Crit Care Med 2004;32:2183–2190.
34. Leone M, Bourgoin A, Cambon S, Dubuc M, Albanese J, Martin C. Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome. Crit Care Med 2003;31:462–467.
35. Morel J, Casoetto J, Jospe R, Aubert G, Terrana R, Dumont A, Molliex S, Auboyer C. De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospec-tive study in a medico-surgical intensive care unit. Crit Care 2010;14R225.
36. Heenen S, Jacobs F, Vincent JL. Antibiotic strategies in severe nosocomial sepsis: why do we not de-escalate more often? Crit Care Med 2012;40:1404–1409.
37. Shime N, Kosaka T, Fujita N. De-escalation of antimicrobial therapy for bacteraemia due to difficult-to-treat Gram-nega-tive bacilli. Infection 2013;41:203–210.
38. Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, Corcia-Palomo Y, Fernandez-Delgado E, Herrera-Melero I, Ortiz-Leyba C, Marquez-Vacaro JA. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 2014;40:32–40.
39. Mokart D, Slehofer G, Lambert J, Sannini A, Chow-Chine L, Brun JP, Berger P, Duran S, Faucher M, Blache JL, Saillard C, Vey N, Leone M. De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Intensive Care Med 2014;40:41–49.
40. Hoffken G, Niederman MS. Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU. Chest 2002;122:2183–2196.
41. Leone M, Bechis C, Baumstarck K, Lefrant JY, Albanese J, Jaber S, Lepape A, Constantin JM, Papazian L, Bruder N, Allaouchiche B, Bezulier K, Antonini F, Textoris J, Martin C. AZUREA Network Investigators. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 2014;40:1399–1408.
42. Zadroga R, Williams DN, Gottschall R, Hanson K, Nordberg V, Deike M, Kuskowski M, Carlson L, Nicolau DP, Sutherland C, Hansen GT. Comparison of 2 blood culture media shows significant differences in bacterial recovery for patients on antimicrobial therapy. Clin Infect Dis 2013;56:790–797.
43. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001;108:1169–1174.
44. Peters RP, van Agtmael MA, Danner SA, Savelkoul PH, Vandenbroucke-Grauls CM. New developments in the diag-nosis of bloodstream infections. Lancet Infect Dis 2004;4:751–760.
45. Tissari P, Zumla A, Tarkka E, Mero S, Savolainen L, Vaara M, Aittakorpi A, Laakso S, Lindfors M, Piiparinen H, Mäki M, Carder C, Huggett J, Gant V. Accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform: an observational study. Lancet 2010;375:224–230.
46. Westh H, Lisby G, Breysse F, Böddinghaus B, Chomarat M, Gant V, Goglio A, Raglio A, Schuster H, Stuber F, Wissing H, Hoeft A. Multiplex real-time PCR and blood culture for identification of bloodstream pathogens in patients with suspected sepsis. Clin Microbiol Infect 2009;15:544–551.
47. Dyar OJ, Huttner B, Schouten J, Pulcini C. ESGAP (ESCMID Study Group for Antimicrobial stewardshiP). What is antimicrobial stewardship? Clin Microbiol Infect 2017;23:793–798.
48. Society for Healthcare Epidemiology of America. Infectious Diseases Society of America. Pediatric Infectious Diseases Society. Policy Statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect Control Hosp Epidemiol 2012;33:322–327.
49. McGowan JE Jr, Gerding DN. Does antibiotic restriction prevent resistance? New Horiz 1996;4:370–376.
50. Centers for Disease Control and Prevention. Core elements of hospital antibiotic stewardship programs [Internet] Atlanta: US Department of Health and Human Services; 2014. cited 2019 Oct 20. Available from: http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html.
51. Burston J, Adhikari S, Hayen A, Doolan H, Kelly ML, Fu K, Jensen TO, Konecny P. A role for antimicrobial stewardship in clinical sepsis pathways: a prospective interventional study. Infect Control Hosp Epidemiol 2017;38:1032–1038.
52. Reinhart K, Bauer M, Riedemann NC, Hartog CS. New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 2012;25:609–634.
53. Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Mélot C, Vincent JL. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003;123:2043–2049.
54. Silvestre J, Coelho L, Povoa P. Should C-reactive protein con-centration at ICU discharge be used as a prognostic marker? BMC Anesthesiol 2010;1017.
55. Tschaikowsky K, Hedwig-Geissing M, Braun GG, Radespiel-Troeger M. Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis. J Crit Care 2011;26:54–64.
56. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalci-tonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis 2013;13:426–435.
57. Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med 2011;171:1322–1331.
58. Prkno A, Wacker C, Brunkhorst FM, Schlattmann P. Procal-citonin-guided therapy in intensive care unit patients with severe sepsis and septic shock--a systematic review and meta-analysis. Crit Care 2013;17R291.
59. Matthaiou DK, Ntani G, Kontogiorgi M, Poulakou G, Arma-ganidis A, Dimopoulos G. An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care Med 2012;38:940–949.
60. Hoeboer SH, van der Geest PJ, Nieboer D, Groeneveld AB. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect 2015;21:474–481.
61. Jeon K, Suh JK, Jang EJ, Cho S, Ryu HG, Na S, Hong SB, Lee HJ, Kim JY, Lee SM. Procalcitonin-Guided Treatment on Duration of Antibiotic Therapy and Cost in Septic Patients (PRODA): a multi-center randomized controlled trial. J Korean Med Sci 2019;34e110.
62. Kopterides P, Siempos II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med 2010;38:2229–2241.
Article information Continued
© Korean Medical Association
Korean Medical Association
