Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial

Trials, December 2012

23249501

Guy Thwaites, Cressida Auckland, Gavin Barlow, Richard Cunningham, Gerry Davies, Jonathan Edgeworth, Julia Greig, Susan Hopkins, Dakshika Jeyaratnam, Neil Jenkins, Martin Llewelyn, Sarah Meisner, Emmanuel Nsutebu, Tim Planche, Robert C Read, Matthew Scarborough, Marta Soares, Robert Tilley, M Estée Török, John Williams, Peter Wilson, Sarah Wyllie, A Sarah Walker

Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection's severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation.