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Case study: ARREST

Staphylococcus aureus is a type of bacteria that can cause range of infections from skin infections such as boils and impectigo to food poisoning and abscesses. However it becomes particularly serious and potentially life threatening, when the bacteria infects the blood stream (bacteraemia). This includes diseases such as MRSA, pneumonia, meningitis or sepsis, which can result in death in 25 per cent of cases.

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ARREST

ARREST - Adjunctive Rifampicin to Reduce Early mortality from STaphylococcus aureus bacteraemia

Staphylococcus aureus is a type of bacteria that can cause range of infections from skin infections such as boils and impectigo to food poisoning and abscesses. However it becomes particularly serious and potentially life threatening, when the bacteria infects the blood stream (bacteraemia). This includes diseases such as MRSA, pneumonia, meningitis or sepsis, which can result in death in 25 per cent of cases.

Approximately 12,500 cases of staphylococcus aureus occur in the UK each year, killing an estimated 3,000 patients and costing the NHS around £225 million.

With less than 1,600 people participating in trials to determine the best treatment option for staphylococcus aureus bacteraemia there was a limited evidence base until the ARREST trial.

Current UK guidelines recommend at least 14 days of antibiotic treatment for staphylococcus aureus bacteraemia. Rifampicin is often considered as a second antibiotic. This is because the drug can be given orally, kills bacteria in cells and tissues where other antibiotics work less well, serious side-effects are relatively rare, and it is cheap (daily oral dose: 15p). However, only three trials involving less than 250 patients in total have investigated whether rifampicin improves outcome from severe staphylococcus aureus disease. The combined results suggest rifampicin may halve the risk of treatment failure and death. Other studies indicate rifampicin may sterilise the blood faster, which is important as death or complications are more likely the longer bacteria remain in the blood.

The ARREST trial was designed to assess whether adding rifampicin to standard antibiotic treatment for staphylococcus aureus bacteraemia would improve survival from this infection. The study compared rifampicin’s effectiveness by recording the time to bacteriological failure or reoccurrence or death. It also investigated the relationship between the blood concentrations of rifampicin and other antibiotics and their clinical effect.

More than 770 patients with staphylococcus aureus bacteraemia were recruited from 29 NHS hospitals and were randomly assigned to 14 days rifampicin or identical placebo (dummy drug) in addition to their standard treatment. Patients were clinically assessed in hospital at various points over the 14 days while taking the treatment, and then once a week until discharge from the trial at 12 weeks.

Key features

  • Chief Investigator: Professor Guy Thwaites, Professor of Infectious Diseases, Director of Oxford University Clinical Research Unit, Vietnam.
  • Study dates: December 2012 - October 2016
  • Sample size: 772 participants
  • The study recruited from 29 sites in the UK
  • Funded by NIHR Health Technology Assessment

Outcomes and findings

Adding rifampicin to standard antibiotic treatment did not improve cure rates or reduce death for people with bacterial blood infections.

The results of the study found no significant difference between the rifampicin group (17 per cent) and the placebo group (18 per cent ) in curing or reoccurence of the bacteria, or reduce the death rate within the 12 week trial period. Therefore this difference is not statistically significant to impact a change in practice.

Breakdown of the results:

14.9 per cent of the rifampicin arm and 12.9 per cent of the placebo arm died without bacteriological failure or reoccurrence.

1.1 per cent of the rifampicin arm and 1.3 per cent of the placebo arm experienced bacteriological failure. Neither of these results are statistically significantly.

0.8 per cent of the rifampicin arm and 4.1 per cent of the placebo arm experienced biological reoccurrence. This was statistically significant.

The group being treated with rifampicin experienced more antibiotic or drug trial modyifying adverse events (17 per cent compared to 10 per cent with the placebo) and also had more drug interactions (6.5 per cent compared to 1.5 per cent compared to the placebo).

Value to the NHS

Despite rifampicin not improving the bacterialogical failure or reoccurrence, or improving the death rate of patients with staphylococcus aureus bacteraemia, it is the largest trial for bacteraemia treatment and strengthens the evidence base.

It means microbiologists can update their policies to take account of the trial results in relation to treating patients with staphylococcus aureus bacteraemia.