Seven Versus Fourteen Days of Treatment in Uncomplicated Staphylococcus Aureus Bacteremia

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy of Seven and Fourteen Days of Antibiotic Treatment in Uncomplicated Staphylococcus Aureus Bacteremia: A Randomized, Non-blinded, Non-inferiority Interventional Study

Conditions
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Staphylococcus Aureus Bacteremia

Intervention / Treatment
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* Drug: Antibiotic therapy duration for 7 days


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antibiotic therapy duration for 7 days<br> | Drug: Antibiotic therapy duration for 7 days<br>* Antibiotic therapy for seven days<br>|
| No Intervention: Antibiotic therapy duration for 14 days<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day survival without clinical or microbiological failure to treatment or relapse |  | up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiologically failure to treatment | Verified S. aureus infection of the same genotype as the initial infection | less than 7 days after treatment termination | 
| Microbiologically relapse | Verified S. aureus infection of the same genotype as the initial infection | more than 7 days after treatment termination | 
| Clinical failure to treatment or relapse | Initiation of anti-staphylococcal therapy for more than 48 hours due to suspected recurrence. | Up to day 90 | 
| Mortality | All-cause mortality | Days 14, 28, 90 and 180 | 
| Severe adverse events | grade 3 or above adverse events | Up to 26 weeks | 
| Acute renal injury | A 1.5 fold increase in creatinine or a 25% decrease of the glomerular filtration rate (GFR) | Up to 26 weeks | 
| Clostridium difficile infection | Microbiologically verified C. difficile infection | Up to 26 weeks | 
| Multidrug-resistance organism | Microbiologically verified multidrug-resistance organism | Up to 26 weeks | 
| Health-associated costs | Public health related cost estimated from a general consideration of the expenses associated with hospitalization for SAB. | Up to 26 weeks |