Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia

Inclusion Criteria:

1. Blood culture positive for Staphylococcus aureus (S. aureus).

2. Received 3 to 7 days of definitive IV antimicrobial therapy, defined as:

• Cloxacillin or cefazolin for methicillin-sensitive staphylococcus aureus (MSSA); Vancomycin or ceftaroline for methicillin-resistant staphylococcusaureus (MRSA).

• Proven in-vitro susceptibility and adequate dosing given (as determined by theprincipal investigator).

3. Achieved clearance of bacteraemia, defined as at least one documented latestnegative follow-up blood culture obtained within 72 hours after the initiation ofdefinitive IV antimicrobial therapy.

4. Achieved defervescence, defined as sustained body temperature ≤37.5°C within 48hours before randomization.

5. Able to provide written informed consent to participate trial.

Exclusion Criteria:

1. Evidence of metastatic infection of S. aureus: for example, infective endocarditis,intraabdominal abscess, lung empyema, and osteomyelitis. Radiological investigationssuch as chest X-ray, ultrasound, echocardiogram, and CT scan are not mandatory priorto enrolment, but should be done at the discretion of the treating physician ifclinically indicated.

2. Septic shock, defined as hypotension requiring vasopressors to maintain MAP ≥65 mmHgdespite adequate volume resuscitation.

3. Received more than 5 days of non-study antibiotics as empirical therapy prior toenrolment.

4. Polymicrobial bloodstream infection, defined as isolation of pathogens other than S.aureus from a blood culture obtained prior to randomization. Common skincontaminants such as coagulase-negative staphylococci, Bacillus spp., anddiphtheroid will not be considered to represent polymicrobial infection.

5. Known history of S. aureus infection within the past 3 months.

6. Inability to tolerate oral therapy or poor absorption of oral medications, or notsuitable for ongoing IV therapy (for example, difficult intravenous access)

7. No options of oral antibiotic available for patient due to:

• In vitro resistance of S. aureus to all oral study drugs.

• Known contraindications to receive the active oral study drugs. For example,hypersensitivity reaction to trimethoprim-sulfamethoxazole, thrombocytopeniasecondary to linezolid etc.

• Non-availability of oral study drugs at the study sites.

8. Patient is concomitantly receiving oral antibiotics which are active against S.aureus. For example, trimethoprim-sulfamethoxazole for Pneumocystis jiroveciipneumonia prophylaxis.

9. Presence of a non-removable foreign body such as prosthetic heart valve, vasculargraft, pacemaker, automated implantable cardioverter-defibrillator,ventriculoperitoneal shunt, prosthetic joint, and fracture fixation implant

10. Failure or inability to remove intravascular catheter that is present when firstpositive blood culture was drawn.

11. Known comorbidity that increased the risk of complicated infections:

• End-stage renal disease

• Severe liver disease (Child-Pugh class C)

• Severe immunodeficiency:

• HIV-positive patients with CD4<200 cells/uL or AIDS

• primary immunodeficiency disorders

• high-dose steroid therapy (>1 mg/kg prednisone or equivalent doses givenfor > 4 weeks or planned during intervention)

• immunosuppressive therapy

• neutropenia (<500 neutrophils/μl) at randomization or neutropenia expectedduring intervention phase due to immunosuppressive treatment

• solid organ or hematopoietic stem cell transplantation within the past 6months or planned during treatment period

13.Short life expectancy < 3 months

14.Pregnancy (for women of childbearing potential)