The goal of this open-label, pragmatic, randomized controlled clinical trial is to learn if patients with Staphylococcus aureus bacteremia (SAB) given the intervention of early dual intravenous (IV) antibiotic therapy will decrease duration of bacteremia (< 6 days) and improve outcomes compared to single IV antibiotic therapy.

The main questions this study aims to answer are:

• To decrease SAB duration and improve outcomes by using early dual vs. single agent IV antibiotic therapy
• To accelerate practice transformation of earlier IV to oral (PO) antibiotic transition by switching to PO antibiotic therapy once blood cultures are negative at 72 hours

Participants will be asked to agree to be randomized (like flipping a coin) to receive two or one IV antibiotic(s). Once the infection has cleared, the treatment will be changed to PO antibiotics. As part of usual care, participants will have weekly lab tests for monitoring while on antibiotics, receive a telephone call to see how the participants are doing, and follow up in person or by telephone or video in Infectious Diseases (ID) Clinic. Participant participation will last 12 weeks after the participant is discharged from the hospital.

Inclusion Criteria:

• The patient is hospitalized at J.W. Ruby Memorial Hospital, Berkeley Medical Center, Camden Clark Medical Center, Princeton Community Hospital, Thomas Hospital, United Hospital Center, or Wheeling Hospital
• The patient has been identified to have Staphylococcus aureus bacteremia
• The patient is able to participate in lab monitoring and in-person or telemedicine ID Clinic follow-up

Exclusion Criteria:

• The patient or an appointed medical decision maker is unable to give informed consent
• The patient is a prisoner, pregnant, and/or mentally handicapped
• The patient is determined unsafe for enrollment at the primary team's discretion