Early Oral Step-down Antibiotic Therapy for Uncomplicated Gram-negative Bacteraemia
Gram-negative Bacteraemia
About this trial
This is an interventional treatment trial for Gram-negative Bacteraemia focused on measuring Gram-negative bacteraemia, Early step-down to oral antibiotics, Oral fluoroquinolones, Oral trimethoprim-sulfamethoxazole, Continuing intravenous antibiotics, Health economics evaluation
Eligibility Criteria
Inclusion Criteria:
- One or more set(s) of blood cultures positive for Gram-negative bacteria (GNB) associated with evidence of infection
- Able to be randomised within 72 hours of index blood culture collection
- Age ≥18 years (≥21 in Singapore)
- Latest Pitt bacteraemia score <4
- Patient or legal representative is able to provide informed consent
Exclusion Criteria:
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 computed tomography scan prior to enrolment)
- Undrained moderate-to-severe hydronephrosis
Complicated infections, including but not limited to:
- Necrotising fasciitis
- Empyema
- Central nervous system infections and meningitis
- Endocarditis / endovascular infections
- 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
- 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)
- Bacteraemia is due to a vascular catheter or intravascular materials (e.g. pacing wire, vascular graft) that cannot be removed
- Specific Gram-negative pathogens that cannot be effectively treated with fluoroquinolones or trimethoprim-sulfamethoxazole, including but not limited to, Burkholderia spp. and Brucella spp.
- Index GNB with resistance to fluoroquinolones AND trimethoprim-sulfamethoxazole
- Hypersensitivity to fluoroquinolones AND sulphur drugs as defined by history of rash, urticaria, angiodema, bronchospasm, circulatory collapse or significant adverse reaction following prior administration
- Unable to consume or absorb oral medications for any reason or unsuitable for ongoing intravenous therapy (e.g. no intravenous access)
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
- Current radiation therapy
- 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
- Women who are known to be pregnant or breast-feeding
- Treatment is not with intent to cure the infection (i.e. palliative care)
- Unable to collect patient's follow-up data for at least 30 days post-randomisation for any reason
- Treating doctor deems enrolment into the trial is not in the best interest of the patient
- Previous enrolment in this trial
Sites / Locations
- Tan Tock Seng HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Early step-down to oral antibiotic therapy
Continuing intravenous antibiotic therapy
The oral antibiotic options are fluoroquinolones (most commonly, ciprofloxacin) or trimethoprim-sulfamethoxazole. The recommended doses for patients with normal renal function would be ciprofloxacin 750 mg twice daily (if body weight ≥70 kg) or ciprofloxacin 500 mg twice daily (if body weight <70 kg) or trimethoprim-sulfamethoxazole 5 mg/kg (for trimethoprim component) every 12 hourly or trimethoprim-sulfamethoxazole (160 mg / 800 mg; double strength) two tablets twice daily. Doses may be adjusted in the setting of renal dysfunction. The minimum treatment duration should be 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days due to regimen extension or requirement for prolonged regimen as clinically indicated.
The intravenous antibiotic(s) to be administered will be determined by the treating doctor according to what would be considered standard of care in the hospital site. Commonly used intravenous antibiotics (and doses) for treatment of Gram-negative bacteraemia include ceftriaxone 2 g daily or cefazolin 2 g three times daily. The minimum treatment duration should be 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days due to regimen extension or requirement for prolonged regimen as clinically indicated.