Singer, M. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA : the journal of the American Medical Association 315, 801–810 (2016).
Gaieski, D. F., Edwards, J. M., Kallan, M. J. & Carr, B. G. Benchmarking the incidence and mortality of severe sepsis in the United States. Critical care medicine 41, 1167–1174 (2013).
Iwashyna, T. J., Cooke, C. R., Wunsch, H. & Kahn, J. M. Population burden of long-term survivorship after severe sepsis in older Americans. Journal of the American Geriatrics Society 60, 1070–1077 (2012).
Iwashyna, T. J., Ely, E. W., Smith, D. M. & Langa, K. M. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA : the journal of the American Medical Association 304, 1787–1794 (2010).
Ferrer, R. 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. Critical care medicine 42, 1749–1755 (2014).
Rivers, E. et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. The New England journal of medicine 345, 1368–1377 (2001).
The ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. The New England journal of medicine 370, 1683–1693 (2014).
Fink, M. P. Animal models of sepsis. Virulence 5, 143–153 (2014).
Levy, M. M. et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive care medicine 29, 530–538 (2003).
Deutschman, C. S. & Tracey, K. J. Sepsis: current dogma and new perspectives. Immunity 40, 463–475 (2014).
Wiersinga, W. J., Leopold, S. J., Cranendonk, D. R. & van der Poll, T. Host innate immune responses to sepsis. Virulence 5, 36–44 (2014).
Wichterman, K. A., Baue, A. E. & Chaudry, I. H. Sepsis and septic shock--a review of laboratory models and a proposal. J Surg Res. 29, 189–201 (1980).
Buras, J. A., Holzmann, B. & Sitkovsky, M. Animal models of sepsis: setting the stage. Nat. Rev. Drug Discov. 4, 854–865 (2005).
Groeneveld, A. B., Bronsveld, W. & Thijs, L. G. Hemodynamic determinants of mortality in human septic shock. Surgery 99, 140–153 (1986).
Parker, M. M., Shelhamer, J. H., Natanson, C., Alling, D. W. & Parrillo, J. E. Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis. Critical care medicine 15, 923–929 (1987).
Abraham, E., Shoemaker, W. C., Bland, R. D. & Cobo, J. C. Sequential cardiorespiratory patterns in septic shock. Critical care medicine 11, 799–803 (1983).
Kraft, B. D. et al. Development of a novel preclinical model of pneumococcal pneumonia in nonhuman primates. American journal of respiratory cell and molecular biology 50, 995–1004 (2014).
Carraway, M. S. et al. Blockade of tissue factor: treatment for organ injury in established sepsis. American journal of respiratory and critical care medicine 167, 1200–1209 (2003).
Reyes, L. F. et al. A Non-Human Primate Model of Severe Pneumococcal Pneumonia. PloS one 11, e0166092 (2016).
Hinshaw, L. B. et al. Survival of primates in LD100 septic shock following steroid/antibiotic therapy. J Surg Res. 28, 151–170 (1980).
Angus, D. C. & van der Poll, T. Severe sepsis and septic shock. The New England journal of medicine 369, 840–851 (2013).
Singer, M., De Santis, V., Vitale, D. & Jeffcoate, W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 364, 545–548 (2004).
Zanotti-Cavazzoni, S. L. & Goldfarb, R. D. Animal models of sepsis. Critical care clinics 25, 703–719, vii-viii, (2009).
Poli-de-Figueiredo, L. F., Garrido, A. G., Nakagawa, N. & Sannomiya, P. Experimental models of sepsis and their clinical relevance. Shock 30(Suppl 1), 53–59 (2008).
Haden, D. W. et al. Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis. American journal of respiratory and critical care medicine 176, 768–777 (2007).
Redl, H. & Bahrami, S. Large animal models: baboons for trauma, shock, and sepsis studies. Shock 24(Suppl 1), 88–93 (2005).
Matute-Bello, G., Frevert, C. W. & Martin, T. R. Animal models of acute lung injury. American journal of physiology. Lung cellular and molecular physiology 295, L379–399 (2008).
Hinshaw, L. B. et al. Survival of primates in lethal septic shock following delayed treatment with steroid. Circulatory shock 8, 291–300 (1981).
Hinshaw, L. B., Brackett, D. J., Archer, L. T., Beller, B. K. & Wilson, M. F. Detection of the ‘hyperdynamic state’ of sepsis in the baboon during lethal E. coli infusion. The Journal of trauma 23, 361–365 (1983).
Miller, F. J., Mercer, R. R. & Crapo, J. D. Lower Respiratory Tract Structure of Laboratory Animals and Humans: Dosimetry Implications. Aerosol Science and Technology 18, 257–271 (1993).
Crapo, J. D. et al. Morphometric characteristics of cells in the alveolar region of mammalian lungs. The American review of respiratory disease 128, S42–46 (1983).
Plopper, C. G. & Hyde, D. M. The non-human primate as a model for studying COPD and asthma. Pulm Pharmacol Ther. 21, 755–766 (2008).
Haudek, S. B. et al. Lipopolysaccharide dose response in baboons. Shock 20, 431–436 (2003).
Suffredini, A. F. et al. The cardiovascular response of normal humans to the administration of endotoxin. The New England journal of medicine 321, 280–287 (1989).
Hinshaw, L. B. et al. Effectiveness of steroid/antibiotic treatment in primates administered LD100 Escherichia coli. Ann Surg. 194, 51–56 (1981).
Cohen, J. The immunopathogenesis of sepsis. Nature 420, 885–891 (2002).
van Deventer, S. J. et al. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 76, 2520–2526 (1990).
Fiedler, V. B. et al. Monoclonal antibody to tumor necrosis factor--alpha prevents lethal endotoxin sepsis in adult rhesus monkeys. The Journal of laboratory and clinical medicine 120, 574–588 (1992).
van Leenen, D. et al. Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees. Journal of immunology 151, 2318–2325 (1993).
van der Poll, T. et al. Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 83, 446–451 (1994).
Levi, M. et al. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. The Journal of clinical investigation 93, 114–120 (1994).
Levi, M. et al. Differential effects of anti-cytokine treatment on bronchoalveolar hemostasis in endotoxemic chimpanzees. American journal of respiratory and critical care medicine 158, 92–98 (1998).
Emerson, T. E. Jr., Lindsey, D. C., Jesmok, G. J., Duerr, M. L. & Fournel, M. A. Efficacy of monoclonal antibody against tumor necrosis factor alpha in an endotoxemic baboon model. Circulatory shock 38, 75–84 (1992).
van der Poll, T. et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. The Journal of experimental medicine 179, 1253–1259 (1994).
Taylor, F. B. Jr. Staging of the pathophysiologic responses of the primate microvasculature to Escherichia coli and endotoxin: examination of the elements of the compensated response and their links to the corresponding uncompensated lethal variants. Critical care medicine 29, S78–89 (2001).
de Boer, J. P. et al. Activation patterns of coagulation and fibrinolysis in baboons following infusion with lethal or sublethal dose of Escherichia coli. Circulatory shock 39, 59–67 (1993).
Drake, T. A., Cheng, J., Chang, A. & Taylor, F. B. Jr. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. The American journal of pathology 142, 1458–1470 (1993).
Taylor, F. B. Jr., Kinasewitz, G. T. & Lupu, F. Pathophysiology, staging and therapy of severe sepsis in baboon models. J Cell Mol Med. 16, 672–682 (2012).
Taylor, F. B. Jr. et al. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. The Journal of clinical investigation 79, 918–925 (1987).
Kneidinger, R., Bahrami, S., Redl, H., Schlag, G. & Robinson, M. Comparison of endothelial activation during endotoxic and posttraumatic conditions by serum analysis of soluble E-selectin in nonhuman primates. The Journal of laboratory and clinical medicine 128, 515–519 (1996).
Redl, H. et al. Expression of endothelial leukocyte adhesion molecule-1 in septic but not traumatic/hypovolemic shock in the baboon. The American journal of pathology 139, 461–466 (1991).
Creasey, A. A. et al. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. The Journal of clinical investigation 91, 2850–2860 (1993).
Taylor, F. B. Jr. et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circulatory shock 33, 127–134 (1991).
Taylor, F. B. et al. Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli. Blood 91, 1609–1615 (1998).
Minnema, M. C. et al. Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli. Blood 95, 1117–1123 (2000).
de Boer, J. P. et al. Activation of the complement system in baboons challenged with live Escherichia coli: correlation with mortality and evidence for a biphasic activation pattern. Infection and immunity 61, 4293–4301 (1993).
Bengtsson, A. et al. Anti-TNF treatment of baboons with sepsis reduces TNF-alpha, IL-6 and IL-8, but not the degree of complement activation. Scand J Immunol 48, 509–514 (1998).
Silasi-Mansat, R. et al. Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis. Blood 116, 1002–1010 (2010).
Keshari, R. S. et al. Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis. Proceedings of the National Academy of Sciences of the United States of America (2017).
Huang, Y. C. et al. VA/Q abnormalities during gram negative sepsis. Respiration physiology 105, 109–121 (1996).
Capelozzi, V. L. What have anatomic and pathologic studies taught us about acute lung injury and acute respiratory distress syndrome? Current opinion in critical care 14, 56–63 (2008).
Levitt, J. E. & Matthay, M. A. Clinical review: Early treatment of acute lung injury--paradigm shift toward prevention and treatment prior to respiratory failure. Critical care 16, 223 (2012).
Ware, L. B. & Matthay, M. A. The acute respiratory distress syndrome. The New England journal of medicine 342, 1334–1349 (2000).
Matthay, M. A., Ware, L. B. & Zimmerman, G. A. The acute respiratory distress syndrome. The Journal of clinical investigation 122, 2731–2740 (2012).
Idell, S. et al. Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome. The Journal of clinical investigation 84, 695–705 (1989).
Welty-Wolf, K. E. et al. Bacterial priming increases lung injury in gram-negative sepsis. American journal of respiratory and critical care medicine 158, 610–619 (1998).
Welty-Wolf, K. E. et al. Tissue factor in experimental acute lung injury. Seminars in hematology 38, 35–38 (2001).
Tang, H. et al. Sepsis-induced coagulation in the baboon lung is associated with decreased tissue factor pathway inhibitor. The American journal of pathology 171, 1066–1077 (2007).
Welty-Wolf, K. E., Carraway, M. S., Ortel, T. L. & Piantadosi, C. A. Coagulation and inflammation in acute lung injury. Thrombosis and haemostasis 88, 17–25 (2002).
Welty-Wolf, K. E. et al. Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure. American journal of physiology. Lung cellular and molecular physiology 290, L21–31 (2006).
Keshari, R. S. et al. Acute lung injury and fibrosis in a baboon model of Escherichia coli sepsis. American journal of respiratory cell and molecular biology 50, 439–450 (2014).
Silasi-Mansat, R. et al. Complement inhibition decreases early fibrogenic events in the lung of septic baboons. J Cell Mol Med 19, 2549–2563 (2015).
Kinasewitz, G. T., Chang, A. C., Peer, G. T., Hinshaw, L. B. & Taylor, F. B. Jr. Peritonitis in the baboon: a primate model which stimulates human sepsis. Shock 13, 100–109 (2000).
Taylor, F. B. Jr. et al. Staging of the baboon response to group A streptococci administered intramuscularly: a descriptive study of the clinical symptoms and clinical chemical response patterns. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 29, 167–177 (1999).
Jain, S. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. The New England journal of medicine 373, 415–427 (2015).
Berendt, R. F., Long, G. G. & Walker, J. S. Influenza alone and in sequence with pneumonia due to Streptococcus pneumoniae in the squirrel monkey. The Journal of infectious diseases 132, 689–693 (1975).
Philipp, M. T. et al. Experimental infection of rhesus macaques with Streptococcus pneumoniae: a possible model for vaccine assessment. Journal of medical primatology 35, 113–122 (2006).
Dehoux, M. S. et al. Compartmentalized cytokine production within the human lung in unilateral pneumonia. American journal of respiratory and critical care medicine 150, 710–716 (1994).
Olsen, R. J. et al. Lack of a major role of Staphylococcus aureus Panton-Valentine leukocidin in lower respiratory tract infection in nonhuman primates. The American journal of pathology 176, 1346–1354 (2010).
Chertow, D. S. et al. Influenza A and methicillin-resistant Staphylococcus aureus co-infection in rhesus macaques - A model of severe pneumonia. Antiviral Res 129, 120–129 (2016).
Klevens, R. M. et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA : the journal of the American Medical Association 298, 1763–1771 (2007).
Centers for Disease Control & Prevention. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - United States, May-August 2009. MMWR. Morbidity and mortality weekly report 58, 1071–1074 (2009).
Kallen, A. J. et al. Staphylococcus aureus community-acquired pneumonia during the 2006 to 2007 influenza season. Annals of emergency medicine 53, 358–365 (2009).
Lina, G. et al. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 29, 1128–1132 (1999).
Kobayashi, S. D. et al. Seasonal H3N2 influenza A virus fails to enhance Staphylococcus aureus co-infection in a non-human primate respiratory tract infection model. Virulence 4, 707–715 (2013).
Stearns-Kurosawa, D. J., Lupu, F., Taylor, F. B. Jr., Kinasewitz, G. & Kurosawa, S. Sepsis and pathophysiology of anthrax in a nonhuman primate model. The American journal of pathology 169, 433–444 (2006).
Popescu, N. I. et al. Peptidoglycan induces disseminated intravascular coagulation in baboons through activation of both coagulation pathways. Blood 132, 849–860 (2018).
Grossman, T. H. et al. The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Bacillus anthracis Infection in BALB/c Mice and Cynomolgus Macaques. Antimicrobial agents and chemotherapy 61, https://doi.org/10.1128/AAC.01103-17 (2017).
Savransky, V. et al. Correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the AV7909 anthrax vaccine candidate. Vaccine 35, 4952–4959 (2017).
Vietri, N. J. et al. Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax. Proceedings of the National Academy of Sciences of the United States of America 103, 7813–7816 (2006).
Inglesby, T. V. et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA : the journal of the American Medical Association 287, 2236–2252 (2002).
Marshall, J. C. Such stuff as dreams are made on: mediator-directed therapy in sepsis. Nat Rev Drug Discov 2, 391–405 (2003).
Bevilacqua, M. P. & Nelson, R. M. Selectins. The Journal of clinical investigation 91, 379–387 (1993).
Carraway, M. S. et al. Antibody to E- and L-selectin does not prevent lung injury or mortality in septic baboons. American journal of respiratory and critical care medicine 157, 938–949 (1998).
Tracey, K. J. et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330, 662–664 (1987).
Hinshaw, L. B. et al. Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNF alpha). Circulatory shock 30, 279–292 (1990).
van der Poll, T. et al. Pretreatment with a 55-kDa tumor necrosis factor receptor-immunoglobulin fusion protein attenuates activation of coagulation, but not of fibrinolysis, during lethal bacteremia in baboons. The Journal of infectious diseases 176, 296–299 (1997).
Schlag, G., Redl, H., Davies, J. & Haller, I. Anti-tumor necrosis factor antibody treatment of recurrent bacteremia in a baboon model. Shock 2, 10–18 ; discussion 19-22. (1994).
Reinhart, K. et al. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study. Critical care medicine 29, 765–769 (2001).
Panacek, E. A. et al. Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab’)2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Critical care medicine 32, 2173–2182 (2004).
Abraham, E. et al. Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study. Critical care medicine 29, 2081–2089 (2001).
Abraham, E. et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA : the journal of the American Medical Association 290, 238–247 (2003).
Marlar, R. A., Kleiss, A. J. & Griffin, J. H. Mechanism of action of human activated protein C, a thrombin-dependent anticoagulant enzyme. Blood 59, 1067–1072 (1982).
Taylor, F. B. & Kinasewitz, G. Activated protein C in sepsis. J Thromb Haemost 2, 708–717 (2004).
Bernard, G. R. et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. The New England journal of medicine 344, 699–709 (2001).
Ranieri, V. M. et al. Drotrecogin alfa (activated) in adults with septic shock. The New England journal of medicine 366, 2055–2064 (2012).
Abraham, E. et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. The New England journal of medicine 353, 1332–1341 (2005).
Otterbein, L. E. et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nature medicine 6, 422–428 (2000).
Fredenburgh, L. E. et al. Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia. American journal of physiology. Lung cellular and molecular physiology 309, L834–846 (2015).
Shinohara, M. et al. Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1. American journal of physiology. Lung cellular and molecular physiology 307, L746–757 (2014).
Dalli, J. et al. The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by Inhaled Carbon Monoxide. American journal of respiratory cell and molecular biology 53, 314–325 (2015).
Fredenburgh, L.E. et al. A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS. J. CI Insight 3, pii: 124039 (2018).
Chabot, D. J. et al. Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys. Vaccine 30, 846–852 (2012).
Poliquin, P. G. et al. Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity Animal Model of Critical Illness. Sci Rep. 7, 1204 (2017).
Shade, R. E., Bishop, V. S., Haywood, J. R. & Hamm, C. K. Cardiovascular and neuroendocrine responses to baroreceptor denervation in baboons. The American journal of physiology 258, R930–938 (1990).
Friday, K. E. & Lipkin, E. W. Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model. The American journal of clinical nutrition 51, 470–476 (1990).
Weatherall, D. The use of non-human primates in research. (Academy of Medical Sciences, London, 2006).
Arnason, G. The ethical justification for the use of non-human primates in research: the Weatherall report revisited. Journal of medical ethics 44, 328–331 (2018).
Barnhill, A., Joffe, S. & Miller, F. G. The Ethics of Infection Challenges in Primates. Hastings Cent Rep. 46, 20–26 (2016).