Last reviewed: June 2018
Last updated: July  2018

Sepsis patients who receive prolonged infusion of anti-pseudomonal beta-lactam antibiotics are 30% less likely to die, meta-analysis finds

There has been long-running debate over whether prolonged infusion of intravenous antibiotics, including beta-lactams, is more effective than standard infusion in improving outcomes in sepsis. Now a meta-analysis has found that patients with sepsis who received their intravenous anti-pseudomonal beta-lactam infusion over at least 3 hours were 30% less likely to die than those who received beta-lactam either as a bolus or as a short-term infusion over 1 hour or less (RR 0.7, 95% CI 0.56 to 0.87). The meta-analysis included 22 randomised controlled trials totalling 1876 patients. The authors concluded that the weight of evidence is high for the benefits of prolonged infusion in patients with sepsis. An accompanying editorial called for the prolonged infusion of beta-lactams over at least 3 hours to become standard practice in intensive care unit settings, even though most administration guides still recommend an infusion over 15 to 60 minutes. [127]

See Management: approach See Management: treatment algorithm

Original source of update

Corticosteroids alone do not reduce mortality in patients with septic shock, but may help in combination with a mineralocorticoid

For many years corticosteroids have been recommended as an adjunctive treatment in patients with septic shock who are refractory to fluids and vasopressor agents. Now a large randomised controlled trial (RCT), published in January 2018, has cast doubt on the benefits of this approach. In the trial of 3,658 patients with septic shock, there was no significant difference in 28-day or 90-day mortality between those who received a continuous infusion of hydrocortisone (200 mg per day for 7 days) compared with those who received placebo (90-day mortality of 27.9% in the hydrocortisone group vs 28.8% for placebo). Those who received hydrocortisone did experience faster resolution of shock (median 3 vs 4 days) and were less likely to need a blood transfusion (37.0% vs 41.7%) but there were no significant differences in length of intensive care unit stay or need for renal replacement therapy.

However, in another RCT of patients with septic shock, when hydrocortisone was administered in combination with fludrocortisone, the 90- and 180-day all-cause-mortality rates were significantly lower. [181]

See Management: approach See Management: treatment algorithm

Original source of update



History and exam

Key diagnostic factors

  • presence of risk factors
  • high (>38°C) or low (<36°C) temperature
  • tachycardia
  • tachypnoea
  • acutely altered mental status
  • poor capillary refill, mottling of the skin, or ashen appearance
  • signs associated with specific source of infection
  • low oxygen saturation
  • arterial hypotension
  • decreased urine output
  • cyanosis

Other diagnostic factors

  • purpura fulminans
  • jaundice
  • ileus

Risk factors

  • underlying malignancy
  • age >65 years
  • immunocompromise
  • haemodialysis
  • alcoholism
  • diabetes mellitus
  • recent surgery or other invasive procedures
  • breached skin integrity
  • indwelling lines or catheters
  • intravenous drug misuse
  • pregnancy
  • urban residence
  • lung disease
  • male sex
  • non-white ancestry
  • winter season

Diagnostic investigations

1st investigations to order

  • FBC with differential
  • blood urea and serum electrolytes
  • serum creatinine
  • LFT
  • coagulation studies (INR, aPTT)
  • serum glucose
  • lactate levels
  • CRP
  • blood culture
  • other cultures (e.g., of sputum, stool, urine, wounds, catheters, prosthetic implants, epidural sites, pleural or peritoneal fluid)
  • arterial blood gas (ABG) or venous blood gas (VBG)
  • chest x-ray
  • ECG
Full details

Investigations to consider

  • lumbar puncture
  • echocardiogram (transthoracic or transoesophageal)
  • ultrasound scan
  • CT chest or abdomen
  • serum procalcitonin
Full details

Emerging tests

  • PhenoTest™ BC Kit
Full details

Treatment algorithm


Authors VIEW ALL

Chief Executive

United Kingdom Sepsis Trust

Chief Executive

Global Sepsis Alliance

Programme Director

Survive Sepsis

Consultant in Critical Care and Anaesthesia

Heart of England NHS Foundation Trust




RD has received payment for consultancy on sepsis from Kimal Plc, manufacturers of vascular access devices, from the Northumbria Partnership, a patient safety collaborative, and, where annual leave or other income was compromised in fulfilling his charity duties, from the UK Sepsis Trust. RD has received sponsorship to attend and speak at one meeting from Abbott Diagnostics. He is CEO of the UK Sepsis Trust and Global Sepsis Alliance, and advises HM Government, the World Health Organisation and NHS England on sepsis. Each of these positions demands that he express opinion on strategies around the recognition and management of sepsis.

Consultant Acute Physician & Sepsis Lead

Department of Acute Medicine

Royal Hampshire County Hospital

Hampshire Hospitals NHS Foundation Trust




MIK is a national clinical advisor on sepsis to NHS England and a national clinical advisor on deterioration to NHS Improvement. He was reimbursed for a slide set by Relias Learning.

Specialty Registrar in Gastroenterology and General Medicine

Maidstone and Tunbridge Wells NHS Trust



AS is the clinical fellow to the National Medical Director at NHS Improvement. AS has been sponsored on two occasions by Dr Falk Pharma UK to attend specialist gastroenterology conferences abroad; there was no contractual obligation to disseminate product information.

Consultant in Emergency Medicine

Clinical Academic

University of Plymouth

Lead Doctor

Devon Air Ambulance Trust

Derriford Hospital




TN is a clinical adviser to the UK Sepsis Trust.

Specialty Registrar in Emergency Medicine

Derriford Hospital




EC declares that he has no competing interests.

Dr Ron Daniels, Dr Matt Inada-Kimand, Dr Aamir Saifuddin, Dr Tim Nutbeam, and Dr Edward Berry would like to gratefully acknowledge Dr Lewys Richmond and Dr Paul Kempen, previous contributors to this topic. LR and PK declare that they have no competing interests.

Peer reviewers VIEW ALL

Professor of Medicine

Infectious Disease Division

Rhode Island Hospital

Alpert Medical School of Brown University




SMO declares that he has no competing interests.

Associate Professor

NYU School of Medicine

Medical Director of Critical Care

Bellevue Hospital Center

New York



LE serves as the guidelines co-chair and on the steering committee of the Surviving Sepsis Campaign.

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