Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteremia

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. Previously it has
been shown that antibiotic treatment for many bacterial infections such as
pneumonia and blood-stream infections can safely and significantly be
shortened. 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.

This study has been transitioned to CTIS with ID 2024-515398-90-01 check the CTIS register for the current data.

To determine whether 4 weeks of total antibiotic treatment duration is
non-inferior to 6 weeks in patients with complicated SAB who have responded
well to the initial treatment.

Multi-center, non-inferiority, randomized controlled open trial comparing 4
versus 6 weeks of intravenous antibiotic therapy in patients with complicated
SAB.

Participants will be randomized to stop antibiotic treatment after either 4
weeks (28 days) or 6 weeks (42 days).

All study participants will receive standard of care for complicated SAB
including routine diagnostic work-up, antibiotic therapy, source control (if
indicated) and venipunctures to monitor clinical response and potential
treatment-related toxicity. After hospital discharge, participants will receive
outpatient parenteral antimicrobial treatment (OPAT), if applicable.
Participants will be asked to complete three sets of questionnaires (some by
phone).

Potential risks include inferiority of 4 weeks of antibiotics compared to 6
weeks of treatment, i.e. increased all-cause mortality or disease relapse.
Given the fact that 4 weeks of treatment is already standard of care in some
countries (i.e. the United Kingdom, Belgium), we do not expect this to be the
case. Furthermore, safety margins are built into the study design (i.e.
satisfactory clinical response to initial therapy and absence of infected
prosthetic material are required for inclusion). A DSMB will evaluate mortality
and infection relapse after one-half of the expected events in the intervention
group or control group have occurred.

Patient benefit will be demonstrated if the treatment duration for SAB can be
safely shortened in this study. Withholding unnecessary exposure to antibiotics
would avoid toxicity and complications. The results of this study are expected
to be applicable over 50% of all patients with complicated SAB in The
Netherlands on a yearly basis, based on an ongoing observational study among
patients with this infection.