Crit Care Med 2021;49:e1063-143

JAMA 2016;315:775-87


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Systemic inflammatory response syndrome (SIRS) criteria – sensitive but not specific for infection:

  • temperature >38.3°C or < 36°C

  • heart rate > 90 beats/min

  • respiratory rate > 20 breaths/min or PaCO2 < 32mmHg

  • WBC > 12 x 109/L, < 4 x 109/L or > 10% immature forms


Life-threatening organ dysfunction caused by a dysregulated host response to infection.

Septic shock:

Subset of sepsis with circulatory, cellular, and metabolic dysfunction associated with a higher risk of mortality than sepsis alone. Patients with septic shock are those with hypotension requiring vasopressor therapy to maintain a mean arterial pressure of 65mm Hg or greater AND serum lactate greater than 2mmol/L after adequate fluid resuscitation.


  • Blood cultures. For clinically significant Gram positive bacteremia or candidemia, repeat blood cultures every 48 hours after starting antimicrobial therapy to ensure clearance.

  • Other cultures/investigations including imaging as appropriate according to presentation and suspected source of infection:

    • urine

    • wound

    • sputum for C&S and CXR if respiratory symptoms

    • CSF

    • GI tract if Gram negative bacteremia/sepsis and negative urine culture

    • thick/thin smear for malaria if relevent travel history.

  • Thorough physical examination to rule out septic emboli and other skin manifestations

Antibiotic therapy:

  • Intravenous antibiotic therapy should be started within first hour of recognition of severe sepsis and septic shock, preferably after blood cultures have been taken.

  • Avoid recently (≤ 3 months) used antibiotics.

  • Vancomycin recommended empirically if patient at risk of MRSA.

  • Linezolid recommended empirically if patient immunocompromised and suspected/proven infection with VRE.

  • For proven/suspected candidemia, an echinocandin or fluconazole is recommended empirically. An echinocandin is preferred if:

    • septic shock

    • severe underlying illness

    • recent azole therapy

    • Nakaseomyces glabrata (previously Candida glabrata) proven/nonalbicans Candida not yet speciated.

  • Tailor/narrow antibiotic therapy according to C&S results.

In general, recommended duration of therapy is 7-10 days; 14 days minimum for S. aureus pneumonia/bacteremia. Longer courses may be required in patients with persistent bacteremia (rule out endocarditis), fungemia, slow clinical response, inadequate source control, or neutropenia.


Source control within 12 hours of diagnosis is critical in many causes of severe sepsis/septic shock including:

  • toxic megacolon or Clostridioides (Clostridium) difficile colitis with shock (discontinue inciting antibiotics)

  • ischemic bowel

  • perforated viscus

  • any significant abscesses, e.g. intra-abdominal

  • ascending cholangitis

  • gangrenous cholecystitis

  • necrotizing pancreatitis with infection

  • bacterial empyema

  • mediastinitis

  • purulent tunnel or foreign body infections

  • obstructive uropathy

  • complicated pyelonephritis/perinephric abscess

  • necrotizing soft tissue infections

  • clostridial myonecrosis.

[Kumar Crit Care Clin 2009;25:745]


Failure to clear blood cultures after 3 days of appropriate antimicrobial therapy indicative of:

  • septic thrombophlebitis

  • endocarditis or other endovascular source

  • undrained/metastatic foci.