What was the primary rationale for the SABATO study on early switch from intravenous (IV) to oral antimicrobial therapy in patients with low-risk Staphylococcus aureus bloodstream infection?

The Rationale for the SABATO Study on Early Switch Therapy in S. aureus Bloodstream Infection

The uncertainty about the efficacy and safety of an early switch from IV to oral antimicrobial therapy in low-risk Staphylococcus aureus bloodstream infection patients was the primary rationale for the SABATO study by Kaasch and colleagues. 1

Background on S. aureus Bloodstream Infection Treatment

Traditional management of S. aureus bloodstream infection (SAB) requires at least 14 days of intravenous (IV) antimicrobial therapy for uncomplicated cases and 4-6 weeks for complicated cases, as recommended by the Infectious Diseases Society of America 2. This long-standing practice is based primarily on historical observational research and expert opinion rather than high-quality randomized controlled trials.

The SABATO Study's Primary Rationale

The SABATO trial was designed specifically to address the knowledge gap regarding whether an early switch to oral therapy would be safe and effective in carefully selected low-risk patients. As stated in the original protocol:

• The primary objective was "to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy" 1

• The study aimed to assess whether early oral switch therapy could be implemented without increasing the risk of SAB-related complications (relapsing SAB, deep-seated infection, and attributable mortality) 1

Secondary Considerations in the SABATO Study Design

While addressing efficacy and safety was the primary rationale, the study also acknowledged several secondary considerations:

1. Potential reduction in healthcare costs: Prolonged IV therapy is resource-intensive and expensive 2

2. Reduction in complications of IV therapy: Long-term IV access carries risks including line infections and vascular access complications 2

3. Potential for earlier hospital discharge: This could improve patient quality of life and reduce hospital-associated complications 1

Study Results and Implications

The SABATO trial ultimately demonstrated that in carefully selected low-risk SAB patients, early switch to oral antimicrobial therapy was non-inferior to continued IV therapy, with a primary composite endpoint of 13% in the oral switch group versus 12% in the IV group 2, 3. This finding has significant implications for clinical practice, suggesting that carefully selected patients might safely benefit from shorter IV therapy courses.

Important Considerations for Implementation

When considering early oral switch therapy for SAB patients, clinicians should:

• Carefully assess patients for signs and symptoms of complicated SAB before considering early oral switch therapy 3
• Ensure patients have received 5-7 days of adequate IV antimicrobial therapy before switching 1
• Exclude patients with polymicrobial bloodstream infection, deep-seated infection, hematogenous dissemination, septic shock, prolonged bacteremia, or non-removable foreign bodies 1
• Provide close follow-up after transition to oral therapy 2

The SABATO trial has provided valuable evidence to potentially change practice in the management of low-risk S. aureus bloodstream infections, addressing the primary uncertainty about whether this approach would be safe and effective.