Evaluation of Antibiotic Regimens in Uncomplicated Staphylococcus aureus Bacteremia: A Randomized Study of Clarithromycin and Drug Combinations

The primary objective of this study is to compare the efficacy of 7-day versus 14-day antibiotic treatment regimens in patients with uncomplicated **Staphylococcus aureus bacteremia** (SAB). The study aims to evaluate the impact of these treatment durations on mortality rates, as well as the prevalence of microbiological and clinical failure to treat and recurrence within 90 days of diagnosis. This is clinically relevant as it may inform optimal treatment duration, potentially reducing unnecessary antibiotic exposure and associated risks.

Secondary objectives include exploring the potential to reduce antibiotic consumption and shorten hospital admissions, which could decrease the risk of adverse events and the development of microbial resistance.

The clinical trial involves a total of **20 participants** diagnosed with **Staphylococcus aureus bacteremia**. The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants were selected based on specific criteria, including a positive blood culture for Staphylococcus aureus and the administration of antibiotic treatment with antimicrobial activity against S. aureus within 12 hours of the first positive blood culture. Additionally, participants were required to have a body temperature below 37.8°C at randomization and a negative follow-up blood culture obtained 48-120 hours after microbiological verification of the bacteremia. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** of two different durations of antibiotic treatment in patients with uncomplicated **Staphylococcus aureus bacteremia**. This study is a randomized, non-blinded, non-inferiority interventional trial. Participants will be randomly assigned to receive either 7 or 14 days of antibiotic therapy. The primary objective is to compare the two treatment durations in terms of 90-day survival without clinical or microbiological failure or relapse. Secondary endpoints include all-cause mortality at various time points, microbiological and clinical failure, severe adverse events, and health-associated costs.

The trial is expected to run until December 31, 2025, with recruitment having started on July 20, 2018. Participants will be involved in the study for a maximum of 14 days, corresponding to the longest treatment duration. The study includes several key visits: an initial screening visit to confirm eligibility, follow-up visits to monitor treatment response and adverse events, and an end-of-study visit to assess final outcomes. Inclusion criteria require participants to be at least 18 years old, have a positive blood culture for **Staphylococcus aureus**, and have received appropriate antibiotic treatment within 12 hours of the first positive culture. Exclusion criteria are not specified in the provided data.

Participants may be withdrawn from the study if they experience severe adverse events or if they do not adhere to the study protocol. The trial's design ensures that all participants receive active treatment, with the primary difference being the duration of therapy. This approach allows for a comprehensive assessment of the optimal treatment length for uncomplicated **Staphylococcus aureus bacteremia**, potentially informing future clinical guidelines.

The clinical trial involves the administration of several **experimental medications** to evaluate their efficacy in treating uncomplicated Staphylococcus aureus bacteremia. The medications include **Clarithromycin "Accord"**, which is provided in the form of film-coated tablets. The active substance is **clarithromycin**, administered orally at a maximum daily dose of 500 mg, with a total maximum dose of 7000 mg over a 14-day period.

**Meropenem Fresenius Kabi** is another experimental medication used in this trial. It is a solution for injection/infusion containing **meropenem trihydrate**. This medication is administered intravenously, with a maximum daily dose of 2 g and a total maximum dose of 28 g over the course of 14 days.

**Ceftriaxon "Kalceks"** is provided as a solution for injection/infusion, with **ceftriaxone** as the active substance. It is administered intravenously, with a maximum daily dose of 2 g and a total maximum dose of 28 g over 14 days.

**Cefotaxim "MIP"** is also used in the trial, available as a solution for injection/infusion. The active substance is **cefotaxime**, administered intravenously, with a maximum daily dose of 2 g and a total maximum dose of 28 g over 14 days.

**Piperacillin/Tazobactam "Sandoz"** is administered as a powder for solution for infusion, containing **piperacillin** and **tazobactam**. This medication is given intravenously, with a maximum daily dose of 16 g and a total maximum dose of 224 g over 14 days.

**Bactocin** is provided as a solution for infusion, with **vancomycin hydrochloride** as the active substance. It is administered intravenously, with a maximum daily dose of 2 g and a total maximum dose of 28 g over 14 days.

**Dicloxacillin "Alternova"** is available in hard capsule form, containing **dicloxacillin**. It is administered orally, with a maximum daily dose of 4 g and a total maximum dose of 56 g over 14 days.

**Ertapenem Fresenius Kabi** is a solution for infusion containing **ertapenem sodium**. It is administered intravenously, with a maximum daily dose of 1 g and a total maximum dose of 14 g over 14 days.

**Flucloxacillin "Orion"** is provided as film-coated tablets, with **flucloxacillin** as the active substance. It is administered orally, with a maximum daily dose of 4 g and a total maximum dose of 56 g over 14 days.

**Cefuroxim Fresenius Kabi** is a solution for injection/infusion containing **cefuroxime sodium**. It is administered intravenously, with a maximum daily dose of 6000 mg and a total maximum dose of 84000 mg over 14 days.

**Gentamicin "B. Braun"** is a solution for infusion with **gentamicin** as the active substance. It is administered intravenously, with a maximum daily dose of 5 mg/kg and a total maximum dose of 70 mg/kg over 14 days.

**Benzylpenicillin "Panpharma"** is provided as a solution for injection/infusion, containing **benzylpenicillin sodium**. It is administered intravenously, with a maximum daily dose of 4 million IU and a total maximum dose of 56 million IU over 14 days.

**Linezolid "Teva"** is available as film-coated tablets, with **linezolid** as the active substance. It is administered orally, with a maximum daily dose of 1200 mg and a total maximum dose of 16800 mg over 14 days.

**Cloxacillin "Stragen"** is a solution for injection/infusion containing **cloxacillin sodium**. It is administered intravenously, with a maximum daily dose of 4 g and a total maximum dose of 56 g over 14 days.

**Clindamycin "Abcur"** is provided as a solution for injection/infusion, with **clindamycin** as the active substance. It is administered intravenously, with a maximum daily dose of 1800 mg and a total maximum dose of 25200 mg over 14 days.

**Sulfametoxazol med trimetoprim SAD** is available in tablet form, containing **sulfamethoxazole** and **trimethoprim**. It is administered orally, with a maximum daily dose of 1600 mg and a total maximum dose of 22400 mg over 14 days.

**Daptomycin "Accord Healthcare"** is a solution for injection/infusion containing **daptomycin**. It is administered intravenously, with a maximum daily dose of 10 mg/kg and a total maximum dose of 240 mg/kg over 14 days.

**Moxifloxacin Fresenius Kabi** is a solution for infusion with **moxifloxacin hydrochloride** as the active substance. It is administered intravenously, with a maximum daily dose of 400 mg and a total maximum dose of 5600 mg over 14 days.

**Levofloxacin "Macure"** is provided as film-coated tablets, with **levofloxacin** as the active substance. It is administered orally, with a maximum daily dose of 1000 mg and a total maximum dose of 14000 mg over 14 days.

**Primcillin** is available as film-coated tablets, containing **phenoxymethylpenicillin potassium**. It is administered orally, with a maximum daily dose of 3200 mg and a total maximum dose of 44800 mg over 14 days.

**Amikacin "Macure"** is a solution for injection containing **amikacin**. It is administered intravenously, with a maximum daily dose of 15 mg/kg and a total maximum dose of 360 mg/kg over 14 days.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimen. The trial does not include any non-experimental treatments such as placebo or standard-of-care therapy. The focus is on evaluating the efficacy of the experimental medications in achieving the trial's main objective.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the 90-day survival without clinical or microbiological failure to treatment or relapse in patients treated with 7 days versus 14 days of antibiotic therapy for uncomplicated **Staphylococcus aureus** bacteremia. Secondary endpoints include all-cause mortality at days 14, 28, 90, and 180, microbiological failure to treatment, microbiological relapse, clinical failure to treatment, severe adverse events grade ≥3, **Clostridium difficile** infection, multidrug-resistance organism, health-associated costs related to treatment lengths, desirability of outcome ranking (DOOR), and hospital admissions during follow-up.

Data collection will occur at specified time points, including days 14, 28, 90, and 180, to evaluate the secondary endpoints. The analysis will focus on comparing the outcomes between the two treatment durations, 7 days and 14 days, to determine non-inferiority in terms of efficacy and safety. The trial aims to provide insights into the optimal duration of antibiotic therapy for uncomplicated **Staphylococcus aureus** bacteremia, considering both clinical outcomes and healthcare resource utilization.