TY - JOUR

T1 - Efficacy of seven and fourteen days of antibiotic treatment in uncomplicated Staphylococcus aureus bacteremia (SAB7)

T2 - study protocol for a randomized controlled trial

AU - Thorlacius-Ussing, Louise

AU - Andersen, Christian Østergaard

AU - Frimodt-Møller, Niels

AU - Knudsen, Inge Jenny Dahl

AU - Lundgren, Jens

AU - Benfield, Thomas Lars

PY - 2019

Y1 - 2019

N2 - BACKGROUND: Staphylococcus aureus bacteremia (SAB) is frequently encountered in the hospital setting, and current guidelines recommend at least 14 days of antibiotic treatment for SAB in order to minimize risks of secondary deep infections and relapse. However, evidence to support these treatment recommendations remains scarce. Patients with uncomplicated SAB are known to have a low of risk of recurrence and death. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, duration of hospital admission, and potentially the risk of adverse events. With SAB7 we seek to determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to 14 days of treatment.METHODS/DESIGN: The study is designed as a randomized, non-blinded, non-inferiority, multicenter interventional study. Primary measure of outcome will be 90-day survival without clinical or microbiological failure to treatment or relapse. Secondary outcomes include the prevalence of severe adverse effects, in particular secondary infection with Clostridium difficile, all-cause mortality, as well as public health related costs. Patients identified with uncomplicated SAB who have received 7 days of protocol-approved antibiotics will be eligible for inclusion and randomized 1:1 in two parallel arms to either (i) discontinue antibiotic treatment at day 7 or (ii) to continue antibiotic treatment for a total of 14 days. Main exclusion criteria include signs of complicated SAB, such as the presence of secondary deep infections, persistent bacteremia, and implantable devices. Patients are followed for 6 months with clinical examinations, consecutive blood tests, and registration of adverse events. A total of 284 patients are to be included at ten centers across Denmark. The primary endpoint will be tested with a statistical non-inferiority margin of 10 percentage points.DISCUSSION: SAB 7 will determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe. Results of the study will provide important knowledge on optimized SAB management and could potentially modify the current treatment recommendations.TRIAL REGISTRATION: ClinicalTrails.gov, H-17027414 . Registered on May 2, 2018. The Danish Medicines Agency (EudraCT), 2017-003529-13. Registered on October 30, 2017.

AB - BACKGROUND: Staphylococcus aureus bacteremia (SAB) is frequently encountered in the hospital setting, and current guidelines recommend at least 14 days of antibiotic treatment for SAB in order to minimize risks of secondary deep infections and relapse. However, evidence to support these treatment recommendations remains scarce. Patients with uncomplicated SAB are known to have a low of risk of recurrence and death. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, duration of hospital admission, and potentially the risk of adverse events. With SAB7 we seek to determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to 14 days of treatment.METHODS/DESIGN: The study is designed as a randomized, non-blinded, non-inferiority, multicenter interventional study. Primary measure of outcome will be 90-day survival without clinical or microbiological failure to treatment or relapse. Secondary outcomes include the prevalence of severe adverse effects, in particular secondary infection with Clostridium difficile, all-cause mortality, as well as public health related costs. Patients identified with uncomplicated SAB who have received 7 days of protocol-approved antibiotics will be eligible for inclusion and randomized 1:1 in two parallel arms to either (i) discontinue antibiotic treatment at day 7 or (ii) to continue antibiotic treatment for a total of 14 days. Main exclusion criteria include signs of complicated SAB, such as the presence of secondary deep infections, persistent bacteremia, and implantable devices. Patients are followed for 6 months with clinical examinations, consecutive blood tests, and registration of adverse events. A total of 284 patients are to be included at ten centers across Denmark. The primary endpoint will be tested with a statistical non-inferiority margin of 10 percentage points.DISCUSSION: SAB 7 will determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe. Results of the study will provide important knowledge on optimized SAB management and could potentially modify the current treatment recommendations.TRIAL REGISTRATION: ClinicalTrails.gov, H-17027414 . Registered on May 2, 2018. The Danish Medicines Agency (EudraCT), 2017-003529-13. Registered on October 30, 2017.

KW - Anti-Bacterial Agents/administration & dosage

KW - Bacteremia/diagnosis

KW - Bacterial Load

KW - Denmark

KW - Drug Administration Schedule

KW - Equivalence Trials as Topic

KW - Humans

KW - Length of Stay

KW - Multicenter Studies as Topic

KW - Staphylococcal Infections/diagnosis

KW - Staphylococcus aureus/drug effects

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1186/s13063-019-3357-9

DO - 10.1186/s13063-019-3357-9

M3 - Journal article

C2 - 31046810

VL - 20

SP - 250

JO - Trials

JF - Trials

SN - 1745-6215

ER -