Daptomycin as Adjunctive Therapy for Staphylococcus Aureus Bacteremia (DASH)

The purpose of our study is to examine the effects of a second antibiotic, daptomycin, in combination with a beta lactam antibiotic on treating bloodstream infection caused by methicillin-susceptible S. aureus.

When patients have a blood infection with methicillin-susceptible S. aureus, they will all be treated with the usual standard of care, including abeta-lactam antibiotic, have their blood tested daily for the presence of the infection until they test negative, as well as an ultrasound of the heart to rule out an infection of the heart valves, as well as have any catheters removed (if possible) to ensure adequate control of the infection. This study involves adding a second antibiotic, daptomycin, to the treatment regimen of half of the patients enrolled in this study. Daptomycin is approved by Health Canada for treating blood infections due to Staphylococcus aureus. It is currently not used in combination with a beta-lactam for these infections because there is insufficient evidence of benefit to justify the cost. The study participants will receive an additional daily iv therapy which will consist of either daptomycin or a placebo for a total of five days while admitted to the hospital. During this time, the participants will continue to have their blood drawn to assess for the presence of bacteria. The participants' liver and muscle enzymes will also be measured on the first and fifth day of therapy to test for potential side effects of the daptomycin.

51 patients receiving a daily placebo infusion for five days on top of standard of care treatment for methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia

51 patients receiving daily daptomycin infusion for five days on top of standard of care treatment for MSSA bacteremia

The development of a new deep seated infection (e.g. osteomyelitis, abscess, endocarditis) not present at time of initial bacteremia

The presence of a new positive blood culture occurring after the first negative culture and within 30 days of the initial positive

Inclusion Criteria: Patient has a methicillin susceptible Staphylococcus aureus bacteremia. Exclusion Criteria: Underlying terminal illness Significant contraindication to beta-lactam therapy (i.e. severe allergy, severe adverse drug reaction) Expected death before 5 days Microbiologically confirmed need for concomitant VANCOMYCIN or DAPTOMYCIN

McGill University Health Centre (Royal Victoria Hospital, Montreal Neurological Hospital, and Montreal General Hospital)

We will make this available under the right conditions including the appropriate data sharing agreements and ethics applications under Quebec law.

Cheng MP, Lawandi A, Butler-Laporte G, Paquette K, Lee TC. Daptomycin versus placebo as an adjunct to beta-lactam therapy in the treatment of Staphylococcus aureus bacteremia: study protocol for a randomized controlled trial. Trials. 2018 May 29;19(1):297. doi: 10.1186/s13063-018-2668-6.

Cheng MP, Lawandi A, Butler-Laporte G, De l'Etoile-Morel S, Paquette K, Lee TC. Adjunctive Daptomycin in the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Randomized, Controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e196-e203. doi: 10.1093/cid/ciaa1000.