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

The Rationale for the SABATO Study on Early Switching from IV to Oral Therapy in Low-Risk S. aureus Bloodstream Infection

The uncertainty about the efficacy and safety of an early switch from IV to oral antimicrobial therapy in this patient population was the primary rationale for the SABATO study by Kaasch and colleagues. 1

Background on S. aureus Bloodstream Infection Treatment

S. aureus bloodstream infection (SAB) has traditionally been treated with prolonged courses of intravenous (IV) antimicrobial therapy to prevent complications such as:

• Relapsing bacteremia
• Deep-seated infections
• Metastatic foci
• Attributable mortality

Current guidelines recommend at least 14 days of IV therapy for uncomplicated SAB and 4-6 weeks for complicated cases 2. This approach has been largely based on observational studies and expert opinion rather than high-quality randomized controlled trials.

The SABATO Trial Design and Rationale

The SABATO (Staphylococcus aureus Bacteremia Adaptive Treatment Optimization) trial was designed to address a critical knowledge gap in SAB management. The study investigators recognized that:

1. Prolonged IV therapy carries significant risks:

   • Vascular access complications
   • Line-associated infections
   • Medication-related adverse events
   • Extended hospital stays
   • Increased healthcare costs

2. For carefully selected low-risk patients, these risks might outweigh the benefits of prolonged IV therapy.

3. Prior to SABATO, there was insufficient evidence regarding the safety and efficacy of early transition to oral therapy in low-risk SAB patients.

The trial was designed as a randomized, parallel-group, observer-blinded, clinical non-inferiority trial to determine if early oral switch therapy (OST) was non-inferior to conventional intravenous standard therapy (IST) in patients with low-risk SAB 3.

Evidence from the SABATO Trial Results

The SABATO trial results, published in The Lancet Infectious Diseases, demonstrated that in carefully selected low-risk SAB patients who had received 5-7 days of adequate IV therapy, early switch to oral antimicrobial therapy was non-inferior to continued IV therapy 1.

Key findings:

• The primary composite endpoint (relapsing SAB, deep-seated infection, and attributable mortality) occurred in 13% of the oral switch group versus 12% in the IV group
• The treatment difference was 0.7 percentage points (95% CI -7.8 to 9.1)
• Serious adverse events were comparable between groups (34% in oral switch vs. 26% in IV group)

Clinical Implications

The SABATO trial provides evidence that for carefully selected patients with low-risk SAB:

• Early transition to oral therapy after 5-7 days of IV treatment is safe and effective
• This approach may reduce complications associated with prolonged IV therapy
• Patient selection is critical - patients must be thoroughly assessed for signs of complicated SAB

Important Caveats

The trial emphasizes the importance of:

• Careful patient selection (excluding those with complicated SAB)
• Appropriate initial IV therapy (5-7 days)
• Close follow-up after transition to oral therapy
• Choosing appropriate oral antimicrobial agents

The findings challenge the traditional paradigm of mandatory prolonged IV therapy for all SAB patients and suggest that a more nuanced, risk-stratified approach may be appropriate.

In conclusion, the SABATO trial was designed to address the uncertainty about the efficacy and safety of early switch from IV to oral antimicrobial therapy in low-risk SAB patients, which was previously an unresolved question in infectious disease management.