Efficacy and Safety of an Early Oral Switch in

Low-Risk Staphylococcus aureus Bloodstream

Infection (SABATO)
Michael Commons
PGY1 Pharmacy Resident
Franciscan Health-Indianapolis

Kaasch AJ et al. Efficacy and safety of an early oral switch in low-risk

Staphylococcus aureus bloodstream infection (SABATO)
doi:10.1016/S1473-3099(23)00756-9
 OBJECTIVES
• Identify the proper treatment of S. aureus bloodstream infections
• Recognize new literature supporting the switch to oral antibiotics
 BACKGROUND
• Rationale:
• No previous randomized controlled trials have evaluated MSSA
bloodstream infections with oral therapy
• Studies have evaluated other organisms when converting to oral
therapy
 GUIDELINES: INTRAVASCULAR CATHETER-
RELATED INFECTIONS
Remove catheter: 5-7 Catheter retained add lock
Coag-negative staph
days systemic therapy therapy for 10-14 days

S. aureus Remove catheter Antibiotics ≥14 days

Enterococcus Remove catheter Antibiotics 7-14 days

Gram-negative
Remove catheter Antibiotics 7-14 days
bacilli

Antifungal 14 days after first

Candida spp. Remove catheter
negative blood culture

Leonard A, et al Clinical Practice Guidelines for Intravascular Catheter-Related Infections https://doi.org/10.1086/599376

 CATHETER-RELATED BLOODSTREAM
INFECTION: NONINFERIORITY OF LINEZOLID
Methods N= 169

• Noninferiority study, open-label, phase 3, and randomized 1:1

Comparator Groups

• Linezolid 600 mg 600 mg every 12 hours; N=95

• Vancomycin/Oxacillin/Dicloxacillin; N=74

Endpoints

• Primary: microbiologic outcome at test of cure 1-2 weeks after treatment

Wilcox MH, et al. Complicated skin and skin-structure infections and catheter-related bloodstream infectionsdoi:10.1086/595686
 CATHETER-RELATED BLOODSTREAM
INFECTION: NONINFERIORITY OF LINEZOLID

Linezolid Control 95% CI

Bloodstream infection 82/95 (86.3) 67/74 (90.5) -13.8-5.4

S. aureus 46/56 (82.1) 35/42 (83.3) -16.3-13.9

MRSA 21/26 (80.8) 18/21 (85.7) -26.2-16.4

Wilcox MH, et al. Complicated skin and skin-structure infections and catheter-related bloodstream infectionsdoi:10.1086/595686
WHY CAN WE NOT EXTRAPOLATE OTHER
ORGANISMS FOR MSSA?

Metastatic foci Relapse rate

Late metastatic
complications
Study Design N= 213

• Randomized, prospective, open-label, and non-inferiority study

• Organism: S. aureus
• Study groups:
• Intravenous
• N= 105
• Oral
• N= 108
 OUTCOMES
• Complications related to S. aureus bloodstream
Primary infection within 90 days
• Recurrent S. aureus bloodstream infection, deep-
seated infection, or death

• Length of stay from first positive blood culture

• Complications from intravenous medication
• C. difficile
Secondary • Survival: 14, 30, and 90-day
• Adverse events
 INCLUSION

Initiated intravenous
antimicrobials within 72
hours of + blood culture
≥1 + blood Negative repeat blood
≥ 18 years old culture with S. cultures obtained within
aureus 24-96 hours
Received 5-7 days of
intravenous
antimicrobials
 Exclusion

- Signs/symptoms of complicated bloodstream infection

- Septic shock within 4 days of randomization
- Positive blood cultures ≥72 hours
- Body temperature >38C before randomization
- Catheters not replaced within 4 days of positive culture
- Patients with higher a-priori score
- MSSA in past 3 months
- IVDU
- Immunocompromised
- Heart valve or vascular graft
 BASELINE CHARACTERISTICS

Variable Oral n=108 Intravenous n=105

Age 64.4 (16.8) 62.6 (17.6)
Male 71 (66%) 77 (73%)
BMI kg/m2 27.6 (6.7) 25.6 (5.4)
TTE/TEE 69 (64%) 60 (57%)
CRP 35 (13-70) 23 (10-59)
Hospital time prior to randomization 10 (7-14) 11 (7-15)
BASELINE INFECTION CHARACTERISTICS

Variable Oral n=108 Intravenous n=105

Peripheral venous catheter 64.4 (16.8) 62.6 (17.6)
Central venous catheter 71 (66%) 77 (73%)
Skin and soft-tissue 26 (24%) 22 (21%)
Other* 5 (5%) 4 (4%)
Unknown 6 (6%) 8 (8%)
*Urinary, pulmonary, cholecystitis
 STATISTICS
• Non-inferiority
• Originally wanted a 5% non-inferiority margin
• Needed 430 participants
• Ended up with 126 participants
• Allowed for a 10% non-inferiority margin
• Utilized intention-to-treat
 PRIMARY ENDPOINT
Intention-to-Treat
Oral Switch Intravenous Percentage point difference
N=108 N=105 (95% CI)
S. aureus bloodstream infection complication 14 (13%) 13 (12%) 0.7 (-7.8-9.1)
≤ 90 days

Clinically Evaluable (Per Protocol)

Oral Switch Intravenous Percentage point difference
N=86 N=79 (95% CI)
S. aureus bloodstream infection complication 3 (4%) 4 (5%) -2.9 (-9.6-3.9)
≤ 90 days
INCIDENCE OF PRIMARY OUTCOME
 SECONDARY ENDPOINTS: INTENTION-TO-
TREAT

Intention-to-Treat
Oral Switch Intravenous Percentage point difference
N=108 N=105 (95% CI)
Length of Stay 12 (9-19) 16 (10-19) -2(-4-0); p=0.043
Intravenous Complications 9 (9%) 17 (17%) -7.9 (-17.6-1.9)
C. difficile Infections 2 (2%) 2 (2%) -0.1 (-3.8-3.6)
14-Day Survival 98.1% 100% -1.9 (-4.5-0.7)
30-Day Survival 94.3% 96% -5.4 (-7.6-4.2)
90-Day Survival 83.6% 89% -5.4 (-14.8-4)
 SECONDARY ENDPOINTS: PER PROTOCOL

Per Protocol
Oral Switch Intravenous Percentage point difference
N=86 N=79 (95% CI)
Length of Stay 11 (9-16) 15 (10-18) -2 (-5-0); p=0.02
Intravenous Complications 6 (7%) 13 (17%) -9.5 (-20.5-1.5)
C. difficile Infections 2 2%) 1 (1%) 1.1 (-4-6.1)
14-Day Survival 98.8% 100% -1.2 (-3.4-1.1)
30-Day Survival 98.8% 98.7% 0.1 (-3.3-3.5)
90-Day Survival 92.9% 94.8% -1.9 (-9.3-5.5)
 Strengths Weaknesses
• The only randomized controlled trial for • Narrow patient population
S. aureus • Uncomplicated bloodstream infections
• Relatively large study • No Hoosier units
• Non-US based study
• Different antibiotics
• Composite primary endpoint
• Intention-to-treat
 CONCLUSION
• Study is the first of its’ kind for S. aureus and is a step in the
right direction for utilizing more oral agents
• Not enough evidence to use for most MSSA bloodstream
infections
QUESTIONS?
 Efficacy and Safety of an Early Oral
Switch in Low-Risk Staphylococcus
aureus Bloodstream Infection
(SABATO)

Michael Commons
PGY1 Pharmacy Resident
Franciscan Health-Indianapolis

Kaasch AJ et al. Efficacy and safety of an early oral switch in low-risk

Staphylococcus aureus bloodstream infection (SABATO)
doi:10.1016/S1473-3099(23)00756-9