Barriers to the effective treatment of sepsis: Antimicrobial agents, sepsis definitions, and host-directed therapies

Annals of the New York Academy of Sciences

Volumn 1323, Issue 1, 2014, Pages 101-114

  Lyle, Ngan H ^a   Pena, Olga M ^a   Boyd, John H ^a   Hancock, Robert E W ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

Antimicrobial resistance; Host directed therapies; Immunology; Sepsis; Sepsis definitions

Indexed keywords

ANTIINFECTIVE AGENT;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; ARTICLE; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; IMMUNE STATUS; OUTCOME ASSESSMENT; SEPSIS; TREATMENT INDICATION; HOST-DIRECTED THERAPIES; IMMUNOLOGY; REVIEW; SEPSIS DEFINITIONS;

ANTIMICROBIAL RESISTANCE; HOST-DIRECTED THERAPIES; IMMUNOLOGY; SEPSIS; SEPSIS DEFINITIONS;

ANTI-INFECTIVE AGENTS; HUMANS; SEPSIS;

EID: 84907956165     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/nyas.12444     Document Type: Article

References (106)

1. MacArthur, R.D. et al. 2004. Adequacy of early empiric antibiotic treatment and survival in severe sepsis: experience from the MONARCS trial. Clin. Infect. Dis. 38: 284-288.
2. Angus, D.C. et al. 2001. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit. Care Med. 29: 1303-1310.
3. Slade, E., P.S. Tamber & J.L. Vincent . 2003. The surviving sepsis campaign: raising awareness to reduce mortality. Crit. Care 7: 1-2.
4. Pallasch, T.J. 2003. Antibiotic resistance. Dent. Clin. North Am. 47: 623-639.
5. Jones, K.E. et al. 2008. Global trends in emerging infectious diseases. Nature 451: 990-993.
6. Hays, J. 2009. The Burdens of Disease. Rutgers University Press. New Brunswick, NJ.
7. Rolinson, G.N. 1961. "Celbenin"-resistant Staphylococci. Br. Med. J. 1: 125.
8. National Nosocomial Infections Surveillance System. 2004. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am. J. Infect. Control 32: 470-485.
9. Appelbaum, P.C. 2012. 2012 and beyond: potential for the start of a second pre-antibiotic era? J. Antimicrob. Chemother. 67: 2062-2068.
10. Rodríguez-Baño, J. et al. 2006. Bacteremia due to extended-spectrum beta -lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge. Clin. Infect. Dis. 43: 1407-1414.
11. Livermore, D.M. et al. 2007. CTX-M: changing the face of ESBLs in Europe. J. Antimicrob. Chemother. 59: 165-174.
12. Livermore, D.M. 2012. Fourteen years in resistance. Int. J. Antimicrob. Agents 39: 283-294.
13. Li, J. et al. 2006. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect. Dis. 6: 589-601.
14. Prasad, P. et al. 2012. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin. Infect. Dis. 54: 1699-1709.
15. Kollef, M.H. et al. 1999. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 115: 462-474.
16. Ibrahim, E.H. et al. 2000. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 118: 146-155.
17. Harbarth, S. et al. 2003. Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am. J. Med. 115: 529-535.
18. Garnacho-Montero, J. et al. 2003. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit. Care Med. 31: 2742-2751.
19. Kumar, A. et al. 2009. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 136: 1237-1248.
20. Kumar, A. et al. 2006. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit. Care Med. 34: 1589-1596.
21. Dellinger, R.P. et al. 2013. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit. Care Med. 41: 580-637.
22. Paolucci, M., M.P. Landini & V. Sambri . 2010. Conventional and molecular techniques for the early diagnosis of bacteraemia. Int. J. Antimicrob. Agents 36(Suppl 2): S6-S16.
23. Lyle, N. & J. Boyd . 2013. The potential for PCR based testing to improve diagnosis and treatment of sepsis. Curr. Infect. Dis. Rep. 15: 372-379.
24. Johnson, M.T. et al. 2011. Impact of previous antibiotic therapy on outcome of Gram-negative severe sepsis. Crit. Care Med. 39: 1859-1865.
25. Aliberti, S. et al. 2012. Stratifying risk factors for multidrug-resistant pathogens in hospitalized patients coming from the community with pneumonia. Clin. Infect. Dis. 54: 470-478.
26. Russell, J.A. 2006. Management of sepsis. N Engl J Med 355: 1699-1713.
27. Fjell, C.D. et al. 2013. Cytokines and signaling molecules predict clinical outcomes in sepsis. PLoS One 8: e79207.
28. Russell, J.A. et al. 2013. Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock. Am. J. Respir. Crit. Care Med. 188: 356-364.
29. Bone, R.C., C.J. Grodzin & R.A. Balk . 1997. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest 112: 235-243.
30. Xiao, W. et al. 2011. A genomic storm in critically injured humans. J. Exp. Med. 208: 2581-2590.
31. Hotchkiss, R.S., G. Monneret & D. Payen . 2013. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat. Rev. Immunol. 13: 862-874.
32. Boomer, J.S. et al. 2011. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 306: 2594-2605.
33. Russell, J.A. et al. 2008. Vasopressin versus norepinephrine infusion in patients with septic shock. N. Engl. J. Med. 358: 877-887.
34. Kellum, J.A. et al. 2007. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch. Intern. Med. 167: 1655-1663.
35. Rigato, O. & R. Salomao . 2003. Impaired production of interferon-gamma and tumor necrosis factor-alpha but not of interleukin 10 in whole blood of patients with sepsis. Shock 19: 113-116.
36. Werdan, K. et al. 2007. Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study. Crit. Care Med. 35: 2693-2701.
37. Rice, T.W. et al. 2010. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit. Care Med. 38: 1685-1694.
38. Abraham, E. et al. 1995. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA 273: 934-941.
39. Cohen, J. & J. Carlet . 1996. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit. Care Med. 24: 1431-1440.
40. Abraham, E. et al. 2001. Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1, 342 patients. Crit. Care Med. 29: 503-510.
41. Opal, S.M. et al. 1997. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit. Care Med. 25: 1115-1124.
42. Mullard, A. 2011. Drug withdrawal sends critical care specialists back to basics. Lancet 378: 1769.
43. McCulloh, R. & S.M. Opal . 2013. Human recombinant lactoferrin for sepsis: too good to be true? Crit. Care Med. 41: 908-909.
44. Verhoef, J. et al. 1996. Issues in the adjunct therapy of severe sepsis. J. Antimicrob. Chemother. 38: 167-182.
45. Riedemann, N.C., R.-F. Guo & P.A. Ward . 2003. Novel strategies for the treatment of sepsis. Nat. Med. 9: 517-524.
46. Goldenberg, N.M. et al. 2011. Broken barriers: a new take on sepsis pathogenesis. Sci. Transl. Med. 3: 88ps25.
47. Lodise, T.P., B. Lomaestro & G.L. Drusano . 2007. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin. Infect. Dis. 44: 357-363.
48. Dulhunty, J.M. et al. 2013. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin. Infect. Dis. 56: 236-244.
49. Chamot, E. et al. 2003. Effectiveness of combination antimicrobial therapy for Pseudomonas aeruginosa bacteremia. Antimicrob. Agents Chemother. 47: 2756-2764.
50. Micek, S.T. et al. 2010. Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis. Antimicrob. Agents Chemother. 54: 1742-1748.
51. Kumar, A. et al. 2010. Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit. Care Med. 38: 1773-1785.
52. Webster, L.T. 1930. The role of microbic virulence, dosage, and host resistance in determining the spread of bacterial infections among mice: I. Pasteurella lepiseptica and Pasteurella aviseptica infections. J. Exp. Med. 52: 901-907.
53. Acute Respiratory Distress Syndrome Network. 2000. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N. Engl. J. Med. 342: 1301-1308.
54. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. et al. 2006. Comparison of two fluid-management strategies in acute lung injury. N. Engl. J. Med. 354: 2564-2575.
55. Boyd, J.H. et al. 2011. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit. Care Med. 39: 259-265.
56. Bone, R.C. et al. 1992. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101: 1644-1655.
57. Levy, M.M. et al. 2003. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 29: 530-538.
58. Funk, D.J., J.E. Parrillo & A. Kumar . 2009. Sepsis and septic shock: a history. Crit. Care Clin. 25: 83-101.
59. Geroulanos, S. & E.T. Douka . 2006. Historical perspective of the word "sepsis." Intensive Care Med. 32: 2077.
60. Bone, R.C. et al. 1989. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit. Care Med. 17: 389-393.
61. Vincent, J.L. et al. 2013. Sepsis definitions: time for change. Lancet 381: 774-775.
62. Heffner, A.C. et al. 2010. Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department. Clin. Infect. Dis. 50: 814-820.
63. Klein Klouwenberg, P.M.C. et al. 2012. Classification of sepsis, severe sepsis and septic shock: the impact of minor variations in data capture and definition of SIRS criteria. Intensive Care Med. 38: 811-819.
64. Nguyen, D.B. et al. 2013. Invasive Methicillin-resistant Staphylococcus aureus infections among patients on chronic dialysis in the United States, 2005-2011. Clin. Infect. Dis. 57: 1393-1400.
65. Institute for Health Metrics and Evaluation. 2013. The Global Burden of Disease: Generating Evidence, Guiding Policy. Seattle, WA: IHME.
66. Lozano, R. et al. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: 2095-2128.
67. Sriskandan, S. 2011. Severe peripartum sepsis. J. R. Coll. Physicians Edinb. 41: 339-346.
68. Stoll, B.J. et al. 2011. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 127: 817-826.
69. Pinsky, M.R. et al. 1993. Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest 103: 565-575.
70. Bernard, G.R. et al. 2001. Efficacy and safety of recombinant human activated protein C for severe sepsis. N. Engl. J. Med. 344: 699-709.
71. Sutherland, A.M. & K.R. Walley . 2009. Bench-to-bedside review: association of genetic variation with sepsis. Crit. Care 13: 210.
72. Abraham, E. et al. 2005. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N. Engl. J. Med. 353: 1332-1341.
73. Nadel, S. et al. 2007. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 369: 836-843.
74. Ranieri, V.M. et al. 2012. Drotrecogin alfa (activated) in adults with septic shock. N. Engl. J. Med. 366: 2055-2064.
75. Annane, D. et al. 2013. Recombinant human activated protein C for adults with septic shock: a randomized controlled trial. Am. J. Respir. Crit. Care Med. 187: 1091-1097.
76. Ziegler, E.J. et al. 1991. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N. Engl. J. Med. 324: 429-436.
77. Marks, L. 2012. The birth pangs of monoclonal antibody therapeutics: the failure and legacy of Centoxin. MAbs 4: 403-412.
78. Murphy, S.T. & M.C. Bellamy . 2013. The quest for the magic bullet. Trends Anaesth. Crit. Care 3: 316-319.
79. Derkx, B., J. Wittes & R. McCloskey . 1999. Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock. European Pediatric Meningococcal Septic Shock Trial Study Group. Clin. Infect. Dis. 28: 770-777.
80. McCloskey, R.V. et al. 1994. Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group. Ann. Intern. Med. 121: 1-5.
81. Greenman, R.L. et al. 1991. A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group. JAMA 266: 1097-1102.
82. Bone, R.C. et al. 1995. A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group. Crit. Care Med. 23: 994-1006.
83. Angus, D.C. et al. 2000. E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators. JAMA 283: 1723-1730.
84. Fisher, C.J. et al. 1994. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. Crit. Care Med. 22: 12-21.
85. Fisher, C.J. et al. 1994. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA 271: 1836-1843.
86. Cohen, J., S. Opal & T. Calandra . 2012. Sepsis studies need new direction. Lancet Infect. Dis. 12: 503-505.
87. Moreno, R.P. et al. 2008. Sepsis mortality prediction based on predisposition, infection and response. Intensive Care Med. 34: 496-504.
88. Rubulotta, F. et al. 2009. Predisposition, insult/infection, response, and organ dysfunction: a new model for staging severe sepsis. Crit. Care Med. 37: 1329-1335.
89. Nguyen, H.B. et al. 2012. Comparison of predisposition, insult/infection, response, and organ dysfunction, acute physiology and chronic health evaluation II, and mortality in emergency department sepsis in patients meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle. J. Crit. Care 27: 362-369.
90. Granja, C. et al. 2013. The predisposition, infection, response and organ failure (PIRO) sepsis classification system: results of hospital mortality using a novel concept and methodological approach. PLoS One 8: e53885.
91. Chen, Y.-X. & C.-S. Li . 2013. Evaluation of community-acquired sepsis by PIRO system in the emergency department. Intern. Emerg. Med. 8: 521-527.
92. De Groot, B. et al. 2013. The prognostic performance of the predisposition, infection, response and organ failure (PIRO) classification in high-risk and low-risk emergency department sepsis populations: comparison with clinical judgement and sepsis category. Emerg. Med. J. doi:10.1136/emermed-2012-202165.
93. Llewelyn, M.J. & J. Cohen . 2007. Tracking the microbes in sepsis: advancements in treatment bring challenges for microbial epidemiology. Clin. Infect. Dis. 44: 1343-1348.
94. Legrand, M. et al. 2010. The response of the host microcirculation to bacterial sepsis: does the pathogen matter? J. Mol. Med. 88: 127-133.
95. Gardy, J.L. et al. 2009. Enabling a systems biology approach to immunology: focus on innate immunity. Trends Immunol. 30: 249-262.
96. Martin, G.S., D.M. Mannino & M. Moss . 2006. The effect of age on the development and outcome of adult sepsis. Crit. Care Med. 34: 15-21.
97. Girard, T.D., S.M. Opal & E.W. Ely . 2005. Insights into severe sepsis in older patients: from epidemiology to evidence-based management. Clin. Infect. Dis. 40: 719-727.
98. Opal, S.M., T.D. Girard & E.W. Ely . 2005. The immunopathogenesis of sepsis in elderly patients. Clin. Infect. Dis. 41(Suppl 7): S504-512.
99. Briel, M. et al. 2006. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection. Cochrane Database Syst. Rev. Issue 3. Art. No.: CD006150. DOI: 10.1002/14651858.CD006150.
100. Danai, P.A. et al. 2006. The epidemiology of sepsis in patients with malignancy. Chest 129: 1432-1440.
101. Shah, B.R. & J.E. Hux . 2003. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 26: 510-513.
102. Schuetz, P., P. Castro & N.I. Shapiro . 2011. Diabetes and sepsis: preclinical findings and clinical relevance. Diabetes Care 34: 771-778.
103. Koh, G.C.K.W. et al. 2012. The impact of diabetes on the pathogenesis of sepsis. Eur. J. Clin. Microbiol. Infect. Dis. 31: 379-388.
104. Krinsley, J.S. 2003. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin. Proc. 78: 1471-1478.
105. Falciglia, M. et al. 2009. Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis. Crit. Care Med. 37: 3001-3009.
106. Díaz-Martín, A. et al. 2012. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality. Crit. Care 16: R223.