Staphylococcus Aureus Bacteremia
Conditions
Brief summary
Introduction: Staphylococcus aureus bacteremia (SAB) plays an important role in long-course antibiotic therapy. Current international guidelines recommend fourteen days of intravenous antibiotic treatment for SAB in order to minimize risks of secondary deep infections and complications. However, patients with simple SAB are known to have a low risk of complications. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, adverse events and duration of hospital admission. SAB7 seeks to determine if seven days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to fourteen days of treatment. Method: The study is designed as a randomized, non-blinded, non-inferiority interventional study. Primary measure of outcome will be failure to treatment or recurrence of SAB twelve weeks after termination of antibiotic treatment. As a measure of secondary outcome the prevalence of severe adverse effects will be evaluated, in particular secondary infection with Clostridium difficile, mortality as well as public health related costs. Patients identified with uncomplicated SAB, are randomized 1:1 in two parallel arms to seven or fourteen days of antimicrobial treatment, respectively. Endpoints will be tested with a statistical non-inferiority margin of 10%. Conclusion: SAB 7 will determine if seven days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe, potentially modifying current treatment recommendations.
Interventions
DRUGAntibiotic therapy duration for 7 days
Antibiotic therapy for seven days
Sponsors
Thomas Benfield
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Blood culture positive for Staphylococcus aureus * Antibiotic treatment with antimicrobial activity to S. aureus administrated within 12 hours of the first positive blood culture * Temperature \< 37,5 degrees celsius at randomization * S. aureus negative follow-up blood culture obtained 48-96 hours after microbiological verified SAB. * Patients written consent obtained
Exclusion criteria
* Persistence of S. aureus bacteremia before randomization (S. aureus positive follow-up blood culture obtained 48-96 hours of the first positive blood culture) * Polymicrobial infection * Antibiotic treatment whit no antimicrobial activity to S. aureus administrated more than 12 hours of the first positive blood culture * Endocarditis or other intracardiac infection demonstrated with transthoracic or transesophageal echocardiography * Previous history of endocarditis * Pacemaker or other intracardiac implant * Failure to remove a likely focus of infection, such as central venous catheter within 72 hours of the first positive blood culture. * Prosthetics in joints and bones or vascular grafts * Pneumonia or infection involving bone or joints * Previously bone/join infection * S. aureus infection within the last 90 days * Pregnancy or breastfeeding * Neutropenia (blood neutrophils \< 1,0 x 109/l) * Untreated cancer * Chemotherapy within 90 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 90-day survival without clinical or microbiological failure to treatment or relapse | up to 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microbiologically relapse | more than 7 days after treatment termination | Verified S. aureus infection of the same genotype as the initial infection |
| Clinical failure to treatment or relapse | Up to day 90 | Initiation of anti-staphylococcal therapy for more than 48 hours due to suspected recurrence. |
| Mortality | Days 14, 28, 90 and 180 | All-cause mortality |
| Severe adverse events | Up to 26 weeks | grade 3 or above adverse events |
| Microbiologically failure to treatment | less than 7 days after treatment termination | Verified S. aureus infection of the same genotype as the initial infection |
| Clostridium difficile infection | Up to 26 weeks | Microbiologically verified C. difficile infection |
| Multidrug-resistance organism | Up to 26 weeks | Microbiologically verified multidrug-resistance organism |
| Health-associated costs | Up to 26 weeks | Public health related cost estimated from a general consideration of the expenses associated with hospitalization for SAB. |
| Acute renal injury | Up to 26 weeks | A 1.5 fold increase in creatinine or a 25% decrease of the glomerular filtration rate (GFR) |
Countries
Denmark
Contacts
Primary ContactLouise Thorlacius-Ussing, MD
Backup ContactThomas Benfield, MD, DMSc
Outcome results
None listed