Shortened antibiotic treatment for Gram-negative bacteremia

Short Course Antibiotic Treatment of Gram-negative Bacteremia: A Multicenter, Randomized, Non-blinded, Non-inferiority Interventional Study

This study is testing if a 5-day antibiotic treatment can help people with a serious infection from a urinary tract issue just as well as the usual 7-day treatment.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 380 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hvidovre University Hospital (other)
• Drugs / interventions: Chemotherapy, prednisone
• Locations: 13 sites (Aalborg and 12 other locations)
• Trial ID: NCT04291768 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of a 5-day antibiotic treatment regimen for patients hospitalized with Gram-negative bacteremia originating from a urinary tract infection. Participants will be randomized into two groups: one receiving the shortened treatment and the other receiving the standard treatment of at least 7 days. The primary goal is to assess 90-day survival without clinical or microbiological failure, while secondary outcomes include all-cause mortality and hospital readmission rates. The study aims to determine if a shorter course of antibiotics can be as effective as the longer standard treatment, potentially reducing the risk of antibiotic resistance and adverse effects.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years with a confirmed Gram-negative bacteremia and evidence of a urinary tract infection.

Not a fit: Patients with immunosuppression or those with specific types of Gram-negative infections may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to shorter antibiotic courses for patients, minimizing the risk of antibiotic resistance and side effects.

How similar studies have performed: Other studies have explored shortened antibiotic regimens, but this specific approach for Gram-negative bacteremia is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Age \>18 years
* Blood culture positive for Gram-negative bacteria
* Evidence of urinary tract source of infection (positive urine culture or at least one clinical symptom compatible with urinary tract infection)
* Antibiotic treatment with antimicrobial activity to Gram-negative bacteria administrated within 12 hours of first blood culture
* Temperature \<37.8°C at randomization
* Clinically stabile at randomization (systolic blood pressure \> 90 mm Hg, heart rate \<100 beats/min., respiratory rate \<24/minute, peripheral oxygen saturation \> 90 %)
* Oral and written informed consent

Exclusion Criteria:

* Antibiotic treatment (\>2 day) with antimicrobial activity to Gram-negative bacteria within 14 days of inclusion
* Gram-negative bacteremia within 30 days of blood culture
* Immunosuppression (Untreated HIV-infection, Neutropenia (absolute neutrophil count \< 1.0 x 109/l), Untreated terminal cancer, Receiving immunosuppressive agents (ATC-code L04A), Corticosteroid treatment (≥20 mg/day prednisone or the equivalent for \>14 days) within the last 30 days, Chemotherapy within the last 30 days, Immunosuppressed after solid organ transplantation, Asplenia)
* Polymicrobial growth in blood culture
* Bacteremia with non-fermenting Gram-negative bacteria (Acinetobacter spp, Burkholderia spp, Pseudomonas spp), Brucella spp, or Fusobacterium spp
* Failure to remove source of infection within 72 hours of first blood culture (e.g. change of catheter á demeure)
* Pregnancy or breastfeeding

Where this trial is running

Aalborg and 12 other locations

• University Hospital of Aalborg — Aalborg, Denmark (NOT_YET_RECRUITING)
• University Hospital of Aarhus — Aarhus, Denmark (NOT_YET_RECRUITING)
• Rigshospitalet — Copenhagen, Denmark (NOT_YET_RECRUITING)
• Bispebjerg Hospital — Copenhagen, Denmark (RECRUITING)
• Gentofte Hospital — Hellerup, Denmark (RECRUITING)
• Herlev Hospital — Herlev, Denmark (RECRUITING)
• Herning Hospital — Herning, Denmark (NOT_YET_RECRUITING)
• Nordsjaellands Hospital — Hillerød, Denmark (RECRUITING)
• Hvidovre Hospital — Hvidovre, Denmark (RECRUITING)
• Kolding Hospital — Kolding, Denmark (NOT_YET_RECRUITING)
• Odense University Hospital — Odense, Denmark (NOT_YET_RECRUITING)
• Roskilde Hospital — Roskilde, Denmark (NOT_YET_RECRUITING)
• Regionshospitalet Silkeborg — Silkeborg, Denmark (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Sandra Tingsgård, MD — Hvidovre University Hospital
• Study coordinator: Sandra Tingsgård, MD

Conditions: Gram-negative Bacteremia, Urinary Tract Infection Bacterial, Gram-negative bacteremia, Urinary tract infection, Shortened antibiotic treatment, Bacterial infection