None listed
Conditions
Interventions
Drug : Randomisation into the intervention or standard arms will be performed with a 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 hours from the time of index blood
Sponsors
Samsung Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria will be non-restrictive allowing a representative and generalisable cohort of eligible participants including elderly patients: 1. =1 set of blood cultures positive for 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
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. Sepsis as defined by infection with consequent acute organ dysfunction or septic shock as defined by systolic blood pressure <90 or mean arterial pressure <70 mmHg despite adequate fluid resuscitation 4. Polymicrobial bacteraemia involving Gram-positive pathogens or anaerobes (defined as either growth of ?2 different microorganism species in the same blood culture, or growth of different species in ?2 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| all-cause mortality at day 30 post-randomisation in patients from the standard arm versus intervention arm | — |
Secondary
| Measure | Time frame |
|---|---|
| All-cause mortality at days 14 and 90 from the time of randomisation ;Duration of survival from the time of randomisation until day 90;Number of days on IV antibiotic therapy in the total index hospitalisation (including outpatient parenteral antibiotic therapy [OPAT]) for surviving participants from the time of randomisation until i. hospital discharge and ii. day 90 ;Number of days alive and free of antibiotics (i. for all antibiotics and ii. for IV antibiotics) between the time of randomisation and day 90 ;Adverse events from the time of randomisation until day 90 including: C. difficile-associated diarrhoea, Peripherally inserted central catheter and other central venous catheter complications (such as catheter-related bloodstream infection, catheter-related superficial or deep venous thrombosis/thrombophlebitis, catheter blockage, and exit site infection) requiring line removal during index hospitalisation (including OPAT) from the time of randomisation, Liver function test abnormalities or acute kidney injury ;Change in treatment strategy between the time of randomisation and day 30 due to: An adverse event deemed by the treating doctor to be of sufficient severity to change treatment strategy, Presumed lack of efficacy of treatment strategy according to the judgement of treating doctor;Time to being discharged alive from the total index hospitalisation (including OPAT and hospital in the home) between the time of randomisation and day 90 ;Number of days alive and not in hospital (including OPAT) between the time of randomisation and day 90;Readmission or extended hospitalisation by day 90. Readmission is defined as a new hospitalisation for any cause or a return to ambulatory hospital services occurring after discharge from the index hospitalisation. Extended hospitalisation is defined as >14 days of hospital LOS starting from the day of randomisation.;Health economic evaluation, including estimation of total healthcare cost (from healthcare system and patien | — |
Countries
Korea, Republic of
Contacts
Public ContactJinyoung Yang
Samsung Medical Center
Outcome results
None listed