Improving the treatment of severe respiratory infections and sepsis

Research led by Professor Paul Dark, Professor of Critical Care Medicine, is helping clinicians treat severe respiratory infections and sepsis more precisely. The work aims to ensure patients receive life-saving antibiotics when needed, while avoiding treatment for longer than necessary.

When respiratory infection leads to sepsis

Respiratory tract infections are the most common cause of sepsis in the UK and worldwide. Infections such as pneumonia can become life-threatening, particularly in people who are older, have weakened immune systems or live with chronic lung conditions.

Sepsis is life-threatening organ dysfunction caused by the body’s dysregulated response to infection. Although it is an unusual complication, it can be triggered by any infection and is the most common reason people die from infectious diseases.

Respiratory tract infections are its leading cause. A patient may arrive at hospital seriously unwell with pneumonia or another infection affecting the lungs, which then triggers the harmful response associated with sepsis.

People at the extremes of age and those with weakened immune systems are particularly vulnerable. Respiratory infections can also develop during hospital care, particularly following surgery or long periods of immobility.

Recognising when a respiratory infection is becoming more severe is therefore an important part of preventing organ damage and improving a patient’s chances of recovery.

The challenge of treating severe infection

Severe respiratory infections can be difficult to assess in critically ill patients. Symptoms such as breathlessness, inflammation and organ dysfunction may suggest infection, but similar signs can also appear when illness has another cause.

Because delaying treatment for bacterial pneumonia or sepsis can be dangerous, clinicians may need to begin broad-spectrum antibiotics before the cause of illness is confirmed. This creates a difficult balance. Antibiotics can save lives, but unnecessary or prolonged treatment can cause side effects.

Unnecessary antibiotic use can also contribute to antimicrobial resistance, making severe respiratory infections and sepsis more difficult to treat in the future.

Clinicians therefore need better tools to recognise when a severe respiratory illness is caused by infection, select the most appropriate treatment and determine when antibiotics can safely be stopped.

Searching for signs of infection

Manchester researchers have spent almost two decades investigating whether blood tests can help clinicians recognise infection and guide treatment safely.

The work has explored both the body’s inflammatory response and molecular traces left by the microorganism causing the infection. This identified promising markers that could help distinguish infection from other causes of critical illness.

One focus has been procalcitonin, a substance in the blood that can rise during bacterial infection and fall as a patient responds to treatment.

Guiding treatment as patients recover

The Manchester-led ADAPT-Sepsis trial tested whether monitoring procalcitonin could help clinicians tailor the length of antibiotic treatment to each patient’s recovery.

The study involved 2,760 critically ill adults across 41 NHS intensive care units. It found that using the blood test reduced antibiotic treatment, without increasing risk to patients. Using this new precision medicine approach, on average 20% of antibiotics can be saved for sepsis patients, it is cost effective and has now been incorporated into international sepsis care guidance.

The findings apply to patients who had already started antibiotics and support decisions about when treatment can safely stop.

For people recovering from pneumonia or another severe respiratory infection, this could mean shorter, more personalised treatment based on how their body is responding.

Across healthcare systems, the approach could reduce side effects, lower costs and help preserve the effectiveness of antibiotics.

Manchester research influencing care

The work builds on Manchester’s strengths in respiratory infection, critical care, diagnostics and clinical trials.

Researchers across the University and its NHS partners are examining the full treatment pathway: identifying respiratory infection, selecting the most suitable antibiotic, determining the correct dose and deciding when treatment should stop.

Manchester’s specialist laboratories help move diagnostic approaches from early research into clinical studies and frontline care.

The findings have contributed to international recommendations on using procalcitonin to support decisions about stopping antibiotics. They could also inform future NICE guidance and how sepsis is treated across NHS hospitals.

Moving towards precision care

The longer-term ambition is to develop more personalised care for severe respiratory infection and sepsis.

Patients respond differently depending on factors including their immune system, genetics, age, health and environment. Manchester researchers are investigating how information about each patient can be combined with evidence about the infection to guide treatment more accurately.

The aim is to help clinicians identify respiratory infection quickly, provide the right antibiotic at the right dose and stop treatment safely.

By connecting respiratory medicine, laboratory research and critical care, Manchester is improving treatment for severe respiratory infections and sepsis while helping protect the future effectiveness of antibiotics.