Early Intravenous to Oral Antibiotic Switch in Uncomplicated Staphylococcus Aureus Bacteraemia

Exclusion Criteria

• •1. Evidence of metastatic infection of S. aureus: for example, infective endocarditis, intraabdominal abscess, lung empyema, and osteomyelitis. Radiological investigations such as chest X-ray, ultrasound, echocardiogram, and CT scan are not mandatory prior to enrolment, but should be done at the discretion of the treating physician if clinically indicated.
• •2. Septic shock, defined as hypotension requiring vasopressors to maintain MAP ≥65 mmHg despite adequate volume resuscitation.
• •3. Received more than 5 days of non-study antibiotics as empirical therapy prior to enrolment.
• •4. Polymicrobial bloodstream infection, defined as isolation of pathogens other than S. aureus from a blood culture obtained prior to randomization. Common skin contaminants such as coagulase-negative staphylococci, Bacillus spp., and diphtheroid 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 not suitable 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, thrombocytopenia secondary 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 jirovecii pneumonia prophylaxis.
• •9. Presence of a non-removable foreign body such as prosthetic heart valve, vascular graft, 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 first positive 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 given for \> 4 weeks or planned during intervention)
• •* immunosuppressive therapy
• •* neutropenia (\<500 neutrophils/μl) at randomization or neutropenia expected during intervention phase due to immunosuppressive treatment
• •* solid organ or hematopoietic stem cell transplantation within the past 6 months or planned during treatment period
• •13.Short life expectancy \< 3 months
• •14.Pregnancy (for women of childbearing potential)