University of Leeds: Extended drug treatment for life threatening infections

Hospital patients who develop infections where 10% of sufferers die will be offered double the traditional course of antibiotics in a new trial.

Patients with serious abdominal infections are usually given a two-week course, but often this is unsuccessful. Now, researchers at the Universities of Leeds and York are trialling a month-long course to establish whether it is more effective at clearing up the infection.

The EXTEND trial is funded by the National Institute for Health and Care Research (NIHR) and is co-led by Dr Andrew Kirby, Associate Professor in Leeds’ School of Medicine and an NHS Consultant in Microbiology, and Mr Dermot Burke, Associate Professor in Surgery in Leeds’ School of Medicine.

We want to see if a longer, fixed course of antibiotics saves lives.

Dr Andrew Kirby, School of Medicine
Dr Kirby said: “There can be aversion to prescribing longer courses of antibiotics due to the risk of antimicrobial resistance to the drugs. But these infections are extremely serious and the current treatments do not work for a large proportion of patients. We want to see if a longer, fixed course cures more people – whether it stops the infection coming back, prevents new infections, and saves lives.

Serious abdominal infections happen when the intestine is damaged, usually by bowel surgery or a disease, causing bacteria living in the intestine to leak into the surrounding cavity. These infections are a leading cause sepsis in patients on intensive care units. Sepsis in the UK kills more people than breast, bowel and prostate cancer combined.

Antibiotic resistance
Long courses of antibiotics can be contentious because they may increase the risk of bacteria finding ways to survive the antibiotics, meaning the antibiotics no longer work to fight the infection. Also, there is guidance that four days of antibiotics may be enough to treat serious abdominal infections. The problem with short antibiotic courses is that 20% of patients are not cured and 10% die following their infection.

Currently, doctors rely on blood tests and patient-reported symptoms to assess whether the infection has cleared up. But if the bacteria have not been fully eradicated by the antibiotics, they can start to regrow, resulting in a recurrence of the infection and potentially more episodes of sepsis. This is why researchers now want to establish whether a set 28-day course of antibiotics can cure these infections more effectively than a doctor deciding when to stop the course.

Mr Burke said: “Intra-abdominal infections make patients feel miserable, weary and keep people in hospital for lengthy periods. Improved methods of treatment are greatly needed.”

Important trial
Professor Andrew Ustianowski, NIHR Joint National Infection Specialty Lead, said: “Intra-abdominal infections and sepsis are very serious issues in our populations. We have a variety of antibiotics that can help but we need specific research to inform us on how best to use them, including for how long.

“This NIHR-funded study is therefore an important trial that I expect will have a direct beneficial impact on our future management of these infections.”

The EXTEND trial is due to start in August 2022 and will run for three years. It will follow patients for six months. Half will receive a course of antibiotics prescribed by their doctor, normally for a week or two, and the other half will receive the 28-day course. The trial will be open to patients in hospital with a serious abdominal infection.

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