Lucan · Conditions

Adult sepsis

Australian guidance: eTG Antibiotic — Sepsis + ACSQHC Sepsis Clinical Care Standard

1. Definition and epidemiology

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, as defined by the Third International Consensus Definitions (Sepsis-3). Septic shock is a subset of sepsis in which underlying circulatory and cellular metabolic abnormalities are associated with greater mortality risk than sepsis alone. In Australia in 2017 there were approximately 55,251 cases of sepsis with 8,702 sepsis-related deaths, and the direct cost to the health system is approximately $700 million per year. Sepsis hospitalisation rates in Australia are disproportionately higher among Aboriginal and Torres Strait Islander peoples, people aged over 85 years, and those living in very remote areas or areas of socioeconomic disadvantage.

2. Pathophysiology

Sepsis arises when the normal localised inflammatory response to infection becomes dysregulated and generalised, causing damage to the host's own tissues and organs (Robbins Ch 4). The triggering insult is usually microbial products such as lipopolysaccharide (gram-negative) or peptidoglycan and teichoic acid (gram-positive), which activate pattern recognition receptors including Toll-like receptors on innate immune cells. Downstream activation of NF-kB drives massive release of pro-inflammatory cytokines including tumour necrosis factor-alpha, interleukin-1 and interleukin-6. These mediators cause systemic vasodilation, increased vascular permeability and endothelial dysfunction, producing distributive shock, maldistribution of microcirculatory flow and mitochondrial dysfunction. Simultaneously, activation of the coagulation cascade with simultaneous impairment of fibrinolysis leads to disseminated intravascular coagulation, further reducing oxygen delivery to tissues and precipitating multi-organ failure across the renal, hepatic, pulmonary, cardiovascular and neurological systems.

3. Clinical presentation and diagnostic criteria

Patients typically present with acute onset of fever, rigors or hypothermia, tachycardia, tachypnoea and altered mental state in the context of a likely or confirmed infectious source. Common sources include pneumonia, urinary tract infection, intra-abdominal infection, skin and soft tissue infection, and intravascular catheter infection. The Sepsis-3 criteria define organ dysfunction by an acute change in total Sequential Organ Failure Assessment (SOFA) score of 2 or more points from baseline, reflecting dysfunction across respiratory, coagulation, hepatic, cardiovascular, neurological and renal domains. The lactate-enhanced quick SOFA (LqSOFA) and aggregate scoring systems such as National Early Warning Score (NEWS) or Modified Early Warning Score (MEWS) are supported for early identification of deteriorating patients in acute settings, though no single screening tool is recommended universally. Septic shock is identified clinically by vasopressor requirement to maintain a mean arterial pressure of 65 mmHg or greater and a serum lactate above 2 mmol/L in the absence of hypovolaemia.

4. Investigations and AU-specific cutoffs

Investigations should be obtained simultaneously with resuscitation and must not delay antimicrobial administration. The recommended order is as follows. Blood cultures (at least two sets from separate sites) must be collected before antimicrobials are started. Serum lactate is a mandatory early investigation; a level above 2 mmol/L identifies tissue hypoperfusion and above 4 mmol/L indicates high-risk septic shock. Full blood count, urea, creatinine, electrolytes, liver function tests, coagulation studies, C-reactive protein and procalcitonin should be obtained. A venous blood gas with point-of-care lactate provides rapid metabolic data. Urinalysis and midstream urine culture, chest X-ray, and source-specific specimens (sputum, wound swab, joint aspirate) are collected as clinically indicated. Bedside ultrasound can aid rapid assessment of volume status and cardiac function. Blood lactate measurement is an ACSQHC Sepsis Clinical Care Standard indicator (Indicator 1a) for all patients with suspected sepsis.

5. Management

Sepsis is a time-critical medical emergency managed according to a locally approved clinical pathway. The ACSQHC Sepsis Clinical Care Standard mandates that assessment and treatment begin urgently and that a clinician experienced in recognising and managing sepsis reviews the patient, escalating to a higher level of care when required.

Resuscitation targets a mean arterial pressure of 65 mmHg or greater using intravenous fluid and vasopressors as required. Crystalloid (balanced solution such as Hartmann's or normal saline) is first line at 30 mL/kg over the first hour for sepsis-related hypoperfusion, then reassessed to avoid fluid overload. Noradrenaline is the preferred vasopressor and should be commenced early for refractory hypotension.

When signs of infection-related organ dysfunction are present, appropriate antimicrobials must be started within 60 minutes of recognition. For sepsis without shock and with high likelihood that organ dysfunction is due to infection, antimicrobials should be given immediately and ideally within 1 hour. Blood cultures must be collected immediately before antimicrobials are administered, but must not delay their administration.

For empirical treatment of adults with sepsis or septic shock from a bone or joint source, eTG recommends gentamicin or tobramycin intravenously plus flucloxacillin 2 g intravenously 4-hourly plus vancomycin 25 mg/kg (actual body weight) loading dose up to 3 g. Regimens are modified within 48 hours based on Gram stain and culture results, and aminoglycoside-containing regimens are stopped at 72 hours if susceptibilities are not available. Empirical regimen choice for other sources is guided by the most likely organism and local susceptibility patterns, and should be reviewed daily against culture results and clinical response. Antimicrobial therapy is managed in line with the Antimicrobial Stewardship Clinical Care Standard, including a review within 48 hours from the first dose.

Source control is essential for all patients with an identifiable focus, including drainage of abscesses, removal of infected devices and debridement of necrotic tissue, performed as soon as feasible after initial stabilisation.

6. Pharmacology and AU PBS notes

First-line empirical antimicrobials vary by suspected source and local resistance patterns. For broad-spectrum community-acquired sepsis of unknown source in adults, piperacillin with tazobactam (Tazocin) 4.5 g intravenously 6-hourly is commonly used, with the addition of vancomycin when methicillin-resistant Staphylococcus aureus (MRSA) is possible. Meropenem 1 g intravenously 8-hourly is reserved for patients with known extended-spectrum beta-lactamase (ESBL)-producing organisms or prior eTG escalation criteria. For bone and joint sepsis, the eTG regimen includes flucloxacillin 2 g intravenously 4-hourly (Flopen, Staphcillin), targeting Staphylococcus aureus. In severe penicillin hypersensitivity, cefazolin 2 g intravenously 6-hourly or vancomycin monotherapy is used as per eTG guidance. Aminoglycosides (gentamicin, tobramycin) require weight-based dosing using institution-specific calculators, with therapeutic drug monitoring essential. Vancomycin loading is 25 mg/kg actual body weight rounded to the nearest 125 mg, with subsequent dosing guided by weight and renal function. Corticosteroids (hydrocortisone 200 mg per day as continuous infusion or divided doses) are considered for refractory septic shock unresponsive to adequate fluids and vasopressors. Antimicrobials for sepsis are largely funded through the Pharmaceutical Benefits Scheme under restricted or streamlined benefit categories according to confirmed organism and severity.

7. Complications and monitoring

Major complications include acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), disseminated intravascular coagulation (DIC), hepatic dysfunction, stress cardiomyopathy, secondary infections, and multi-organ failure. Inpatient mortality monitoring is an ACSQHC indicator (Indicator 8a: proportion of patients with sepsis who died during their admitted episode of care), with readmission within 30 days also tracked (Indicator 7a). Monitoring during acute management includes hourly urine output targeting at least 0.5 mL/kg/hour, continuous cardiac monitoring, serial serum lactate (at 2 and 6 hours) to guide resuscitation adequacy, daily renal function and electrolytes, and coagulation studies. Antimicrobial therapy must be reviewed formally at 48 hours with culture results and de-escalated where possible. Survivors of sepsis require individualised follow-up care to manage post-sepsis syndrome, which includes long-term cognitive impairment, physical deconditioning, psychological sequelae including post-traumatic stress disorder, and immune dysregulation with increased susceptibility to recurrent infection. Structured, holistic post-discharge care involving the general practitioner and relevant allied health services is required to optimise functional recovery and minimise rehospitalisation.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.