PassFinals
Infectious Disease

Sepsis

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, in which inflammatory signalling and microvascular failure injure organs remote from the infected site.

In a nutshell

Sepsis is organ dysfunction from a dysregulated response to infection. Grade risk with NEWS2 (National Early Warning Score 2): 7 or more is high risk and needs broad-spectrum IV antibiotics plus a 250 mL crystalloid bolus within 1 hour.

Classic presentation

A 78-year-old with a long-term urinary catheter becomes confused and tachypnoeic, with systolic blood pressure 88 mmHg and temperature 35.8°C.

Key points

  • NEWS2 scores respiratory rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse, consciousness or new confusion, and temperature.
  • SOFA (Sequential Organ Failure Assessment) and qSOFA (quick SOFA) are Sepsis-3 research tools. UK practice uses NEWS2, not qSOFA.
  • Septic shock: vasopressors needed to hold mean arterial pressure at 65 mmHg or more, with lactate over 2 mmol/L despite fluids.
  • Senior clinical decision maker means ST3 or above in adults. FY2 (Foundation Year 2) covers the urgent review and moderate-risk lactate check.
  • NICE added risk factors in 2025: age 75 or over, frailty, immunosuppression, surgery within 6 weeks, catheters, homelessness, communication difficulties.
  • For 16 to 18 year olds with community-acquired sepsis, NICE specifies ceftriaxone 80 mg/kg once daily, maximum 4 g daily.
  • Post-sepsis syndrome causes fatigue, breathlessness, poor concentration and low mood, usually settling over 6 to 18 months.

First-line investigation

Venous blood gas for lactate and glucose, with blood cultures, FBC, CRP, U&E, creatinine, LFTs and clotting, without delaying the 1 hour antibiotic.

Management

Recognise and grade the risk

  • Full observations plus NEWS2: 7 or more high risk, 5 to 6 moderate, 1 to 4 low, 0 very low.5,4
  • Any parameter scoring 3, plus mottling, cyanosis, purpura or deterioration, pushes the patient up a band regardless of the total.5

High risk: the first hour

  • Venous gas (lactate, glucose), blood cultures, FBC, CRP, U&E, creatinine, LFTs, clotting. Sampling must not delay the antibiotic.6
  • Broad-spectrum IV antibiotic within 1 hour of the first NEWS2: piperacillin with tazobactam 4.5 g every 8 hours if the source is unknown.6,16,19
  • 250 mL Hartmann's over 10 to 15 minutes, reassess, repeat to a maximum of 1,000 mL. Oxygen to 94% to 98%, or 88% to 92% if hypercapnic risk.6,11

Match the antibiotic to the source

  • Chest: IV co-amoxiclav 1.2 g every 8 hours plus clarithromycin 500 mg every 12 hours; levofloxacin 500 mg every 12 hours if penicillin-allergic.12
  • Urine: IV co-amoxiclav 1.2 g every 8 hours, ceftriaxone 1 to 2 g daily, or gentamicin 5 to 7 mg/kg daily.13
  • Skin: IV co-amoxiclav 1.2 g every 8 hours, adding vancomycin 15 to 20 mg/kg every 8 to 12 hours if MRSA is likely.14
  • Meningitis: IV ceftriaxone 2 g every 12 hours. Neutropenic sepsis: piperacillin with tazobactam 4.5 g every 6 hours immediately.15,21,17,20
  • Check your trust's antimicrobial guideline, usually MicroGuide, before prescribing; adjust for renal impairment and allergy, and monitor gentamicin and vancomycin levels.11
  • Source control: urinalysis and chest X-ray in everyone, abdominal and pelvic imaging if no focus, then drain, decompress, debride or remove.9

When it is not working

  • No response within 1 hour of any intervention: senior clinical decision maker (ST3 or above) in person, critical care contacted, consultant informed.6,1
  • Shock persisting after 1,000 mL: vasopressors after critical care discussion. Peripheral start needs a visible cannula watched for extravasation.6

Before they leave

  • Narrow the antibiotic once cultures return. Explain the diagnosis, warning signs and how to get urgent help, and tell the GP.11,22,10
  • Check the pathway: NG255 for pregnancy or 4 weeks after birth, NG254 for under-16s, CG151 for neutropenic sepsis.23,24,25,21

Exam traps

  • The Sepsis Six is a UK Sepsis Trust bundle, not a NICE recommendation. NICE timing is risk-stratified, so not everyone needs antibiotics within 1 hour.
  • SIRS no longer defines sepsis. Sepsis-3 replaced it in 2016 with organ dysfunction, and NICE NG253 uses that wording.
  • NEWS2 of 0 is very low risk, not no risk. Purpura, mottling, cyanosis or deterioration override the score.
  • Moderate risk plus lactate over 2 mmol/L or acute kidney injury is high risk: the antibiotic is due within 1 hour, not 3.
  • Persistent shock after 1,000 mL needs vasopressors and critical care, not a fifth bolus.
  • Normal temperature does not exclude sepsis. Older, frail, immunosuppressed and cancer patients, and those with spinal cord injury, often stay afebrile.
  • Recent pregnancy means 4 weeks after birth, or 24 hours after miscarriage or termination, and takes the patient off the NG253 pathway.

Illustrations

Dysregulated host responseDiagram showing infection triggering excessive inflammatory signalling, causing vasodilation, capillary leak and microvascular dysfunction distant from the original site.PassFinals · original
Risk-stratified sepsis pathwayInfographic showing NEWS2 risk bands, the one-hour high-risk pathway, the maximum three-hour moderate-risk window, the maximum six-hour low-risk window, fluids, source control and escalation.PassFinals · original
Purpuric rash in severe sepsisNon-blanching purpuric rash and skin microvascular injury in severe sepsis and meningococcal disease; the same rash may be harder to detect on darker skin tones.Gley A.I. and Shkurba A.V., Wikimedia Commons · Public domain

Key sources

  1. NICE NG253, Terms used in this guideline (NG253)Published 19 Nov 2025
  2. Singer M and others, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA 2016;315(8):801-810 (Sepsis-3)Published 23 Feb 2016
  3. NICE NG253, Could this be sepsis? (NG253)Published 19 Nov 2025
  4. Royal College of Physicians, National Early Warning Score (NEWS) 2 (RCP NEWS2)Published 19 Dec 2017
  5. NICE NG253, Evaluating risk of severe illness or death from sepsis (NG253)Published 19 Nov 2025
  6. NICE NG253, Managing suspected sepsis (NG253)Published 19 Nov 2025
  7. Academy of Medical Royal Colleges, Statement on the initial antimicrobial treatment of sepsis (v2.0) (AoMRC sepsis statement v2.0)
  8. UK Sepsis Trust, information for healthcare professionals and the Sepsis Six (UK Sepsis Trust)
  9. NICE NG253, Finding and controlling the source of infection (NG253)Published 19 Nov 2025
  10. NHS, sepsis (NHS sepsis)Updated 14 May 2026
  11. NICE NG253, Antibiotic therapy, intravenous fluid and oxygen (NG253)Published 19 Nov 2025
  12. NICE NG250, Pneumonia: diagnosis and management, antibiotic choice for adults (NG250)
  13. NICE NG111, Pyelonephritis (acute): antimicrobial prescribing (NG111)Published 31 Oct 2018
  14. NICE NG141, Cellulitis and erysipelas: antimicrobial prescribing (NG141)Published 27 Sept 2019
  15. NICE NG240, Meningitis (bacterial) and meningococcal disease (NG240)Published 19 Mar 2024
  16. Summary of product characteristics, piperacillin 2 g/tazobactam 250 mg powder for solution for infusion (emc SmPC piperacillin with tazobactam)Updated 1 Jun 2022
  17. Summary of product characteristics, ceftriaxone 1 g powder for solution for injection or infusion (emc SmPC ceftriaxone)Updated 12 Aug 2020
  18. Summary of product characteristics, amoxicillin 1 g powder for solution for injection or infusion (emc SmPC amoxicillin)Updated 24 Jul 2023
  19. BNF, piperacillin with tazobactam (BNF piperacillin with tazobactam)
  20. BNF, ceftriaxone (BNF ceftriaxone)
  21. NICE CG151, Neutropenic sepsis: prevention and management in people with cancer (CG151)Published 19 Sept 2012
  22. NICE NG253, Information and support for all people with suspected sepsis (NG253)Published 19 Nov 2025
  23. NICE NG253, Update information (NG253)Published 19 Nov 2025
  24. NICE NG254, Suspected sepsis in under 16s (NG254)
  25. NICE NG255, Suspected sepsis in pregnant or recently pregnant people (NG255)

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.