Unnecessary long-term exposure to antibiotics should be avoided since it increases the risk of adverse events such as renal and hepatic toxicity, health-care-related infections and antibiotic resistance. Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections worldwide. Complicated SAB is typically treated with 6 weeks of antibiotics, but there are no randomized studies to guide this duration. International guidelines are not conclusive and recommend 4 to 6 weeks of treatment.
Our hypothesis is that for patients who have responded well to the initial treatment, a total antibiotic duration of 4 weeks is non-inferior to 6 weeks.
We propose a multi-center, non-inferiority, randomized controlled open trial comparing 4 versus 6
weeks of intravenous antibiotic therapy in patients with complicated SAB.
STUDY POPULATION & INTERVENTION
Adults with methicillin-sensitive complicated SAB in stable condition will be eligible for inclusion. They will be randomized to stop antibiotic treatment after either 4 or 6 weeks and will be followed up for 6 months after treatment cessation. Patients with methicillin-resistant S. aureus (MRSA) infections, with any undrained abscess, or with infected prosthetic material will be excluded.
The primary endpoint is a composite of all-cause mortality or relapse of bacteremia. Secondary outcomes will include antibiotic-related toxicity, perceived quality of life and societal costs.
Assuming a primary endpoint occurrence of 10%, a sample size of n=396 is required in order to prove non-inferiority with a margin of 7.5%, a one-sided a of 0.05 and ß of 0.20. Survival models will be used for the primary time-to-event outcome among intention-to-treat and per-protocol populations.