Last updated: July 27, 2022

Summarytoggle arrow icon

Sepsis is an acute life-threatening condition characterized by organ dysfunction due to a dysregulated immune response to infection. Without prompt intervention, patients frequently progress to septic shock and multiple organ failure. The precipitating infection is often bacterial, typically originating in the respiratory, genitourinary, or gastrointestinal systems or in the skin or soft tissue. Clinical features include fever, tachycardia, confusion, and signs of the primary infection. Sepsis screening tools incorporating common clinical variables and laboratory values are used to facilitate early identification of sepsis. Favorable patient outcomes rely on early detection, effective resuscitation measures (e.g., aggressive fluid therapy and appropriate use of vasopressors), and early administration of antibiotics. The diagnostic workup of sepsis should occur in parallel with resuscitation efforts and focuses on identifying the site of infection and causative pathogen for definitive treatment.

Definitions and criteria in this section apply to adult patients.

Third International Consensus Definitions for Sepsis and Septic Shock [1][2]

  • Sepsis: a severe, life-threatening condition that results from a dysregulation of the patient's response to an infection, causing tissue and organ damage and subsequent organ dysfunction [1]
  • Septic shock: a sepsis syndrome accompanied by circulatory and metabolic abnormalities that can significantly increase mortality [1]

Organ dysfunction secondary to sepsis is defined as an acute increase of ≥ 2 in the total SOFA score due to the infection.

Other definitions of sepsis syndromes [1][3][4][5][6]

  • Systemic inflammatory response syndrome (SIRS) : a group of physiological and immune-mediated reactions that are triggered in response to an infectious or noninfectious insult (e.g., an acute inflammatory process or trauma) [1][3]
  • Sepsis: ≥ 2 SIRS criteria PLUS a suspected or confirmed underlying infection [1]
  • Severe sepsis: sepsis PLUS dysfunction of at least one organ or system [1]
  • Multiple organ dysfunction syndrome (MODS) : [1]
    • Progressive, but potentially reversible, dysfunction of several organs and/or systems [7]
    • The more organs that are affected, the greater the mortality risk.
  • Bacteremia: the presence of viable bacteria in the bloodstream, with or without clinical signs of infection [8]

See also “Etiology of bloodstream infections.”

Implanted devices are an important risk factor and a common source of infection. [1]


Sepsis is a hyperinflammatory systemic reaction.

  1. Local activation of inflammatory mediators (complement system, mast cells, macrophages) results in vessel dilation and further release of proinflammatory cytokines (esp. TNFα, IL-1).
  2. Generalized endothelial disruption → capillary leak → generalized edema due to a shift of intravascular fluid and albumin into the surrounding tissue
  3. Intravascular hypovolemia; → excessive triggering of the extrinsic coagulation cascade disseminated intravascular coagulation (DIC) and microvascular thrombosis
  4. Decreased oxygen utilization and tissue ischemia; → widespread cellular injury → organ dysfunction (commonly multisystem)

An adequate immune response requires a balance between proinflammatory (antiinfectious) and antiinflammatory signals!

The following recommendations are consistent with the 2021 Surviving Sepsis Campaign guidelines and the American College of Emergency Physicians (ACEP) task force consensus statement for adults with suspected sepsis in the emergency department. [2][17]

Sepsis is a medical emergency. Be vigilant for early signs of sepsis and begin treatment as soon as sepsis is suspected.

Approach [2]

Perform diagnostics and treatment simultaneously in patients with suspected sepsis.

Sepsis management is an iterative process requiring frequent reassessments. Favorable outcomes depend on early detection, effective resuscitation, and early administration of antibiotics. [2][17]

Hour-1 bundle for sepsis [2][20][22]

Hour-1 bundle: lactate + cultures + fluids + vasopressors + antibiotics

Disposition [2]

The main goals of the diagnostic workup in a patient with suspected sepsis are to determine the presence and severity of organ dysfunction and to identify the source of infection. See the “Definitions” section for diagnostic criteria. [1][4][22]

Positive cultures are not mandatory for the diagnosis of sepsis.

Sepsis screening tools [2][17]

  • Goal: early identification of patients with sepsis to reduce mortality [2][24]
  • Commonly used tools [24]
    • SIRS criteria [1][3]
    • Quick SOFA score (qSOFA) [25]
      • Can predict poor outcomes; not recommended as a sole screening tool for sepsis [2][26][27]
      • Considered positive if ≥ 2 of the following are present:
  • Limitations: Accuracy is low and can vary. [2][27][28]

The qSOFA score is not recommended as a sole screening tool for sepsis or septic shock. [2]

Laboratory studies

In addition to serum lactate and blood cultures (at least two sets), obtain the following studies to support the diagnosis and evaluate for organ dysfunction.

Identifying the source of infection


When possible, obtain the additional samples before starting antibiotic treatment, but do not delay antibiotics if samples are not rapidly available.


Direct decisions based on clinical suspicion. Examples of commonly performed imaging include:

See also “Immediate hemodynamic support” and “Septic shock.”

IV fluids [29][2]

Vasopressors for septic shock [2][23]

See “Septic shock” and “Vasopressors” for further details.

Consider starting vasopressor infusion through a peripheral IV to avoid delays while awaiting central venous access. [2]

Hemodynamic reassessment in sepsis [2][17][23][30]

Continuously monitor hemodynamic parameters and volume status to guide IV fluids and/or vasopressor therapy.

If possible, use invasive BP monitoring to facilitate continuous reassessment. [2]

Respiratory support [2][36][37]

Respiratory dysfunction is a common feature of sepsis. Patients with sepsis frequently have tachypnea, signs of increased work of breathing, and/or hypoxia.

Shock and metabolic acidosis are both associated with a high risk of peri-intubation mortality. [4][39]

Corticosteroids [2][17]


Empiric antibiotic therapy for sepsis [20][40][41][42][43]

There is little consensus regarding the optimal empiric antibiotic regimens for patients with sepsis and septic shock, especially if the source of infection is unclear.

Evident source of infection [4]

If the source of infection is clear, follow local hospital protocols to administer antibiotics that cover the most common causative pathogens.

Unclear source of infection [40][41][42][51]

The following regimens are examples commonly mentioned in the literature; follow local hospital protocols when available.

Empiric antibiotic regimens for sepsis with unclear source
Patient characteristics Commonly used regimens

Unknown risk factors

At risk for specific pathogens


Antifungal therapy [20]

Source control for sepsis [2][23]

Identify and eliminate sources of infection that cannot be adequately treated with antimicrobials as soon as possible (e.g., within 6–12 hours). [2]

The following is a list of noninfectious conditions that may mimic sepsis. [4][23]

Critical illness polyneuropathy is a common cause of prolonged weaning from mechanical ventilation in patients with sepsis!

We list the most important complications. The selection is not exhaustive.

Interested in the newest medical research, distilled down to just one minute? Sign up for the One-Minute Telegram in “Tips and links” below.

  1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315 (8): p.801-810. doi: 10.1001/jama.2016.0287 . | Open in Read by QxMD
  2. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock. Crit Care Med. 2021 . doi: 10.1097/ccm.0000000000005337 . | Open in Read by QxMD
  3. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med.. 2003; 29 (4): p.530-538. doi: 10.1007/s00134-003-1662-x . | Open in Read by QxMD
  4. Walls R, Hockberger R, Gausche-Hill M. Rosen's Emergency Medicine. Elsevier Health Sciences ; 2018
  5. Seymour CW, Coopersmith CM, Deutschman CS, et al. Application of a Framework to Assess the Usefulness of Alternative Sepsis Criteria. Crit Care Med. 2016; 44 (3): p.e122-e130. doi: 10.1097/ccm.0000000000001724 . | Open in Read by QxMD
  6. Sartelli M, Kluger Y, Ansaloni L, et al. Raising concerns about the Sepsis-3 definitions. World Journal of Emergency Surgery. 2018; 13 (1). doi: 10.1186/s13017-018-0165-6 . | Open in Read by QxMD
  7. Rello J, Kollef MH, Díaz E, Rodríguez A. Infectious Diseases in Critical Care. Springer Science & Business Media ; 2010
  8. Riedel S, Carroll KC. Blood cultures: key elements for best practices and future directions. J Infect Chemother. 2010; 16 (5): p.301-316. doi: 10.1007/s10156-010-0069-1 . | Open in Read by QxMD
  9. Gauer RL. Early recognition and management of sepsis in adults: the first six hours.. Am Fam Physician. 2013; 88 (1): p.44-53.
  10. Kalil A. Septic Shock. Septic Shock. New York, NY: WebMD. Updated: March 17, 2016. Accessed: February 21, 2017.
  11. Sepsis and Septic Shock. Updated: April 1, 2016. Accessed: February 21, 2017.
  12. Neviere R. Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: February 1, 2017. Accessed: February 21, 2017.
  13. Gauer RL. Early Recognition and Management of Sepsis in Adults: The First Six Hours. Am Fam Physician. 2013; 88 (1): p.44-53.
  14. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. . 2003; 348 (16): p.1546-1554. doi: 10.1056/nejmoa022139 . | Open in Read by QxMD
  15. Guideline summary: Sepsis: recognition, diagnosis and early management. Updated: July 13, 2016. Accessed: December 1, 2017.
  16. Gauer RL. Early recognition and management of sepsis in adults: The first six hours. Am Fam Physician. 2013; 88 (1): p.44-53.
  17. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical ; 2018
  18. Hermans G, De Jonghe B, Bruyninckx F, Berghe G. Clinical review: critical illness polyneuropathy and myopathy. Critical Care. 2008; 12 (6): p.238. doi: 10.1186/cc7100 . | Open in Read by QxMD
  19. Rhee C, Chiotos K, Cosgrove SE, et al. Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure. Clinical Infectious Diseases. 2020 . doi: 10.1093/cid/ciaa059 . | Open in Read by QxMD
  20. Yealy DM, Mohr NM, Shapiro NI, Venkatesh A, Jones AE, Self WH. Early Care of Adults With Suspected Sepsis in the Emergency Department and Out-of-Hospital Environment: A Consensus-Based Task Force Report. Ann Emerg Med. 2021; 78 (1): p.1-19. doi: 10.1016/j.annemergmed.2021.02.006 . | Open in Read by QxMD
  21. McLymont N, Glover GW. Scoring systems for the characterization of sepsis and associated outcomes. Ann Transl Med. 2016; 4 (24): p.527-527. doi: 10.21037/atm.2016.12.53 . | Open in Read by QxMD
  22. Lee SM, An WS. New clinical criteria for septic shock: serum lactate level as new emerging vital sign. Journal of Thoracic Disease. 2016; 8 (7): p.1388-1390. doi: 10.21037/jtd.2016.05.55 . | Open in Read by QxMD
  23. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med.. 2017; 43 (3): p.304-377. doi: 10.1007/s00134-017-4683-6 . | Open in Read by QxMD
  24. Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation. 2015; 132 (15): p.1435-1486. doi: 10.1161/CIR.0000000000000296 . | Open in Read by QxMD
  25. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med. 2018; 44 (6): p.925-928. doi: 10.1007/s00134-018-5085-0 . | Open in Read by QxMD
  26. Kalil AC, Gilbert DN, Winslow DL, Masur H, Klompas M. Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines. Clinical Infectious Diseases. 2017; 66 (10): p.1631-1635. doi: 10.1093/cid/cix997 . | Open in Read by QxMD
  27. Septimus EJ, Coopersmith CM, Whittle J, Hale CP, Fishman NO, Kim TJ. Sepsis National Hospital Inpatient Quality Measure (SEP-1): Multistakeholder Work Group Recommendations for Appropriate Antibiotics for the Treatment of Sepsis. Clinical Infectious Diseases. 2017; 65 (9): p.1565-1569. doi: 10.1093/cid/cix603 . | Open in Read by QxMD
  28. Saag MS et al. The Sanford Guide to Antimicrobial Therapy 2016. Antimicrobial Therapy, Inc ; 2016
  29. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019; 200 (7): p.e45-e67. doi: 10.1164/rccm.201908-1581st . | Open in Read by QxMD
  30. Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011; 52 (5): p.e103-e120. doi: 10.1093/cid/ciq257 . | Open in Read by QxMD
  31. 2022 EAU Guideline on Urological Infections. Updated: March 1, 2022. Accessed: May 4, 2022.
  32. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection. Surg Infect (Larchmt). 2017; 18 (1): p.1-76. doi: 10.1089/sur.2016.261 . | Open in Read by QxMD
  33. Ramakrishnan K, Salinas RC, Agudelo Higuita NI. Skin and Soft Tissue Infections.. Am Fam Physician. 2015; 92 (6): p.474-83.
  34. Bury DC, Rogers TS, Dickman MM. Osteomyelitis: Diagnosis and Treatment. Am Fam Physician. 2021; 104 (4): p.395-402.
  35. Chambers HF, Bayer AS. Native-Valve Infective Endocarditis.. N Engl J Med. 2020; 383 (6): p.567-576. doi: 10.1056/NEJMcp2000400 . | Open in Read by QxMD
  36. Bassetti M, Vena A, Croxatto A, Righi E, Guery B. How to manage Pseudomonas aeruginosa infections. Drugs in Context. 2018; 7 : p.1-18. doi: 10.7573/dic.212527 . | Open in Read by QxMD
  37. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy. 2020; 77 (11): p.835-864. doi: 10.1093/ajhp/zxaa036 . | Open in Read by QxMD
  38. Faust JS, Weingart SD. The Past, Present, and Future of the Centers for Medicare and Medicaid Services Quality Measure SEP-1. Emerg Med Clin North Am. 2017; 35 (1): p.219-231. doi: 10.1016/j.emc.2016.09.006 . | Open in Read by QxMD
  39. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of Clinical Criteria for Sepsis. JAMA. 2016; 315 (8): p.762. doi: 10.1001/jama.2016.0288 . | Open in Read by QxMD
  40. Serafim R, Gomes JA, Salluh J, Póvoa P. A Comparison of the Quick-SOFA and Systemic Inflammatory Response Syndrome Criteria for the Diagnosis of Sepsis and Prediction of Mortality. Chest. 2018; 153 (3): p.646-655. doi: 10.1016/j.chest.2017.12.015 . | Open in Read by QxMD
  41. Koch C, Edinger F, Fischer T, et al. Comparison of qSOFA score, SOFA score, and SIRS criteria for the prediction of infection and mortality among surgical intermediate and intensive care patients. World Journal of Emergency Surgery. 2020; 15 (1). doi: 10.1186/s13017-020-00343-y . | Open in Read by QxMD
  42. Almutary A, Althunayyan S, Alenazi K, et al. National Early Warning Score (NEWS) as Prognostic Triage Tool for Septic Patients.. Infect Drug Resist. 2020; 13 : p.3843-3851. doi: 10.2147/IDR.S275390 . | Open in Read by QxMD
  43. Liu VX, Lu Y, Carey KA, et al. Comparison of Early Warning Scoring Systems for Hospitalized Patients With and Without Infection at Risk for In-Hospital Mortality and Transfer to the Intensive Care Unit. JAMA Netw Open. 2020; 3 (5): p.e205191. doi: 10.1001/jamanetworkopen.2020.5191 . | Open in Read by QxMD
  44. Fleuren LM, Klausch TLT, Zwager CL, et al. Machine learning for the prediction of sepsis: a systematic review and meta-analysis of diagnostic test accuracy. Intensive Care Med. 2020; 46 (3): p.383-400. doi: 10.1007/s00134-019-05872-y . | Open in Read by QxMD
  45. Gando S, Shiraishi A, et al. The SIRS criteria have better performance for predicting infection than qSOFA scores in the emergency department. Scientific Reports. 2020; 10 (1). doi: 10.1038/s41598-020-64314-8 . | Open in Read by QxMD
  46. Kalantari A, Rezaie S. Challenging the One-hour Sepsis Bundle. West J Emerg Med. 2019; 20 (2): p.185-190. doi: 10.5811/westjem.2018.11.39290 . | Open in Read by QxMD
  47. Hernández G, Ospina-Tascón GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock. JAMA. 2019; 321 (7): p.654. doi: 10.1001/jama.2019.0071 . | Open in Read by QxMD
  48. Cecconi M, De Backer D, Antonelli M, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014; 40 (12): p.1795-1815. doi: 10.1007/s00134-014-3525-z . | Open in Read by QxMD
  49. Long E, Oakley E, Duke T, Babl FE. Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid Responsiveness. Shock. 2017; 47 (5): p.550-559. doi: 10.1097/shk.0000000000000801 . | Open in Read by QxMD
  50. Pourmand A, Pyle M, Yamane D, Sumon K, Frasure SE. The utility of point-of-care ultrasound in the assessment of volume status in acute and critically ill patients.. World J Emerg Med. 2019; 10 (4): p.232-238. doi: 10.5847/wjem.j.1920-8642.2019.04.007 . | Open in Read by QxMD
  51. Corl KA, George NR, Romanoff J, et al. Inferior vena cava collapsibility detects fluid responsiveness among spontaneously breathing critically-ill patients. J Crit Care. 2017; 41 : p.130-137. doi: 10.1016/j.jcrc.2017.05.008 . | Open in Read by QxMD
  52. Castro R, Kattan E, Ferri G, et al. Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial. Ann Intensive Care. 2020; 10 (1). doi: 10.1186/s13613-020-00767-4 . | Open in Read by QxMD
  53. Magder S. Bench-to-bedside review: Ventilatory abnormalities in sepsis. Critical Care. 2009; 13 (1): p.202. doi: 10.1186/cc7116 . | Open in Read by QxMD
  54. Martin GS, Bernard GR. Airway and lung in sepsis. Intensive Care Med. 2001; 27 (S1): p.S63-S79. doi: 10.1007/pl00003798 . | Open in Read by QxMD
  55. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 . doi: 10.1007/s00134-021-06506-y . | Open in Read by QxMD
  56. Archambault PM, St-Onge M. Invasive and Noninvasive Ventilation in the Emergency Department. Emerg Med Clin North Am. 2012; 30 (2): p.421-449. doi: 10.1016/j.emc.2011.10.008 . | Open in Read by QxMD
  57. Kortenoeven ML, Li Y, Shaw S, et al. Amiloride blocks lithium entry through the sodium channel thereby attenuating the resultant nephrogenic diabetes insipidus. Kidney Int. 2009; 76 (1): p.44-53. doi: 10.1038/ki.2009.91 . | Open in Read by QxMD
  58. Cunha BA. Bacterial Sepsis. Bacterial Sepsis. New York, NY: WebMD. Updated: March 18, 2016. Accessed: February 21, 2017.
  59. SIRS, Sepsis, and Septic Shock Criteria. Updated: March 14, 2017. Accessed: March 14, 2017.
  60. What is qSOFA?. Updated: March 14, 2017. Accessed: March 14, 2017.
  61. Saguil A, Fargo M. Acute Respiratory Distress Syndrome: Diagnosis and Management. Am Fam Physician. 2012; 85 (4): p.352-358.
  62. Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock for the Third International Consensus Definitions for sepsis and septic shock (sepsis-3). JAMA. 2016; 315 (8): p.775-787. doi: 10.1001/jama.2016.0289 . | Open in Read by QxMD
  63. Meisner M. Update on procalcitonin measurements. Ann Lab Med. . 2014; 34 (4): p.263. doi: 10.3343/alm.2014.34.4.263 . | Open in Read by QxMD
  64. Schmidt GA, Mandel J, Parsons PE, Sexton DJ, Hockberger RS, Finlay G. Evaluation and Management of Suspected Sepsis and Septic Shock in Adults . In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: July 20, 2017. Accessed: September 27, 2017.
  65. Goldman L, Schafer AI. Goldman-Cecil Medicine, 2-Volume Set. Elsevier ; 2019
  66. Horcajada JP, Montero M, Oliver A, et al. Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections. Clin Microbiol Rev. 2019; 32 (4). doi: 10.1128/cmr.00031-19 . | Open in Read by QxMD
  67. Shortridge D, Castanheira M, Pfaller MA, Flamm RK. Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015. Antimicrobial Agents Chemother (Bethesda). 2017; 61 (7). doi: 10.1128/aac.00465-17 . | Open in Read by QxMD
  68. Gallagher JC, Satlin MJ, Elabor A, et al. Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: A Multicenter Study. Open Forum Infectious Diseases. 2018; 5 (11). doi: 10.1093/ofid/ofy280 . | Open in Read by QxMD

Access full content

Sign up and get unlimited access.
 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer