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

• Status: Not yet recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Current management of uncomplicated Gram-negative bacteraemia entails prolong intravenous (IV) antibiotic therapy with limited evidence to guide oral conversion. This trial aim to evaluate the clinical efficacy and economic impact of early step-down to oral antibiotics (within 72 hours from index blood culture collection) versus continuing standard of care IV therapy (for at least another 48 hours post-randomisation) for clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tan Tock Seng Hospital
• Collaborators: Changi General Hospital; Imperial College Healthcare NHS Trust; John Hunter Hospital; Melbourne Health; National University Hospital, Singapore; Ng Teng Fong General Hospital; Royal Brisbane and Women's Hospital; Samsung Medical Center; Sengkang General Hospital; Singapore Clinical Research Institute; Singapore General Hospital; University of Malaya
• Treatments: Anti-Bacterial Agents; Cefazolin; Ceftriaxone; Ciprofloxacin; Fluoroquinolones; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Criteria

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 (e.g. cholecystitis)

• Central nervous system abscess (patients with focal neurology should have cranial computed tomography scan 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, 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, angiodema, bronchospasm or circulatory collapse following prior administration

9. Unable to consume or absorb oral medications for any reason or unsuitable for ongoing intravenous 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

• Generalised malignancy

• 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

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