Early Oral Step-down Antibiotic Therapy for Uncomplicated Gram-negative Bacteraemia

Inclusion Criteria: 1. One or more set(s) of blood cultures positive for Gram-negative bacteria (GNB) associated with evidence of infection 2. Able to be randomised within 72 hours of index blood culture collection 3. Age ≥18 years (≥21 in Singapore) 4. Latest Pitt bacteraemia score \<4 5. Patient or legal representative is able to provide informed consent Exclusion Criteria: 1. Established uncontrolled focus of infection, including but not limited to: * Undrained abdominal abscess, deep seated intra-abdominal infection and other unresolved abdominal sources requiring surgical intervention * Central nervous system abscess (patients with focal neurology should have cranial CT prior to enrolment) * Undrained moderate-to-severe hydronephrosis 2. Complicated infections, including but not limited to: * Necrotising fasciitis * Empyema * Central nervous system infections and meningitis * Endocarditis / endovascular infections 3. Septic shock as defined by systolic blood pressure \<90 or mean arterial pressure \<70 mmHg despite adequate fluid resuscitation or need for inotropic/vasopressor support 4. Polymicrobial bacteraemia involving Gram-positive pathogens or anaerobes (defined as either growth of 2 or more different microorganism species in the same blood culture, or growth of different species in 2 or more separate blood cultures within the same episode \[\<48 hours\] and with clinical or microbiological evidence of the same source) 5. Bacteraemia is due to a vascular catheter or intravascular materials (e.g. pacing wire, vascular graft) that cannot be removed 6. Specific Gram-negative pathogens that cannot be effectively treated with fluoroquinolones or trimethoprim-sulfamethoxazole, including but not limited to, Burkholderia spp. and Brucella spp. 7. Index GNB with resistance to fluoroquinolones AND trimethoprim-sulfamethoxazole 8. Hypersensitivity to fluoroquinolones AND sulphur drugs as defined by history of rash, urticaria, angioedema, bronchospasm, circulatory collapse or significant adverse reaction following prior administration 9. Unable to consume or absorb oral medications for any reason or unsuitable for ongoing IV therapy (e.g. no intravenous access) 10. Severely immunocompromised in the opinion of the treating doctor, including but not limited to, medical conditions such as: * Active leukaemia or lymphoma * Aplastic anaemia * Bone marrow transplant within two years of transplantation or transplants of longer duration still on immunosuppressive drugs or with graft-versus-host disease * Congenital immunodeficiency * HIV/AIDS with CD4 lymphocyte count \<200 * Neutropenia or expected post-chemotherapy neutropenia within 14 days from the time of screening, defined as absolute neutrophil count \< 500 cells/μL 11. Women who are known to be pregnant or breast-feeding 12. Treatment is not with intent to cure the infection (i.e. palliative care) 13. Unable to collect patient's follow-up data for at least 30 days post-randomisation for any reason 14. Treating doctor deems enrolment into the trial is not in the best interest of the patient 15. Previous enrolment in this trial