SABATO Trial: Implications for Pharmacists in Staphylococcus Aureus Treatment

Author(s):

Victoria Wright, PharmD,Ron Welch, PharmD, BCPS, BCIDP

Study results indicate early swap to oral antibiotics in Staphylococcus aureus bacteremia is just as effective.

About the Study

Trial Name: Staphylococcus Aureus Bacteremia Antibiotic Treatment Options (SABATO)

ClinicalTrials.gov ID: NCT01792804

Sponsor: Heinrich-Heine University, Duesseldorf

Completion Date (Actual): March 26, 2020

Staphylococcus aureus bacteremia (SAB) bloodstream infections are known to be a critical concern and often require an extended duration of antibiotic therapy. Infectious Diseases Society of America guidelines have also recommended at least 14 days of antibiotics, which was recommended in intravenous (IV) form. The SABATO (Staphylococcus Aureus Bloodstream Infection Antibiotic Treatment Options) trial (NCT01792804) was recently published and has provided evidence to consider switching to oral antibiotics after 5 to 7 days of IV antibiotic therapy in uncomplicated SAB.

Participants in the multicenter, randomized trial were adults diagnosed with low-risk SAB, as determined by specific clinical criteria that excluded endocarditis, prosthetic infections, and other high-risk factors. Eligible patients were randomly assigned to either continue with the standard IV antibiotic regimen or switch to an oral antibiotic regimen within 72 hours of initial treatment.

The primary outcome measure was the success of treatment, defined as the resolution of symptoms without the need for additional antibiotics at 90 days post-treatment. Secondary outcomes included the length of hospital stay after the first positive blood culture to hospital discharge or death, complications of IV administration from the start of the study to the end of follow-up; Clostridium difficile infection; 14-day, 30-day, and up to 90-day survival; adverse events (AEs), and serious AEs.

Patient were included if they were over 18 years of age with SAB isolated from at least one blood culture and were eligible if they had received 5 to 7 days of appropriate IV antimicrobial therapy, initiated within 72 hours after the first positive blood culture was drawn, and at least one follow-up blood culture obtained within 24 to 96 hours after the start of appropriate antimicrobial therapy. Blood cultures taken in this period had to be negative for SAB for the patient to be included.

Blood cultures taken in this period had to be negative for SAB for the patient to be included. Image Credit: © neirfy - stock.adobe.com

Over 5000 patients were assessed for inclusion in the SABATO trial. In total, 165 patients were available for randomization, with 79 in the IV antibiotic only group, and 86 in the oral switch group.

The study excluded patients showing signs of complicated SAB bloodstream infections, including deep-seated infections like endocarditis or pneumonia, septic shock within 4 days before random assignment, prolonged bacteremia, or a body temperature over 38°C before random assignment. Additionally, patients were excluded if intravascular catheters were not removed within 4 days after detecting the infection or if they had a higher risk for complications due to factors like recent infection history, drug use, severe immune system issues, or having a prosthetic heart valve or deep-seated vascular graft.

There were some limitations in the SABATO trial. A significant one was the study included only a few patients with MRSA, which might severely limits the generalizability to real-world practice.

The implications from the SABATO trial allow for pharmacists to continue to advocate for antimicrobial stewardship, IV to oral swap of antibiotics, and optimizing patient care by reducing health care costs. Pharmacists can use the SABATO trial data to push for the appropriate use of antibiotics, promoting an early switch to oral therapy when clinically appropriate. This approach supports the broader goals of antimicrobial stewardship by minimizing unnecessary exposure to IV antibiotics and reducing the risk of resistance.

The study demonstrated that for patients with low-risk SAB, an early switch to oral antibiotics was not inferior to the continuation of IV antibiotic therapy in terms of treatment success. Specifically, the oral therapy group showed similar rates of treatment success, recurrence, and mortality compared to the IV group. Moreover, the switch to oral antibiotics was associated with a lower incidence of AEs, highlighting the safety of this approach. This approach does need to be balanced with carefully assessing the patient for signs and symptoms of complicated SAB.

REFERENCES

Kaasch AJ, López-Cortés LE, Rodríguez-Baño J, et al; SABATO study group. Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2024. doi:10.1016/S1473-3099(23)00756-9