Vancomycin Versus Daptomycin for the Treatment of Methicillin-resistant Staphylococcus Aureus Bacteremia Due to Isolates With High Vancomycin Minimum Inhibitory Concentrations (MICs)

Study Overview
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Brief Summary
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There is an increased failure rate for the treatment of Staphylococcus Aureus Bacteremia (SAB) with traditional doses of vancomycin, the standard of care for patients with MRSA bacteremia over the last 40 years. This has been largely attributed to isolates with increased resistance to vancomycin (increased MIC). Daptomycin is an antibiotic that was approved several years ago for the treatment of SAB and is being increasingly used for MRSA bacteremia due to isolates with increased MIC. Increased doses have been recommended for both of these drugs in the treatment of this infection without a trial demonstrating their relative efficacy or safety at higher doses. This study will randomize patients with SAB due to MRSA with an increased MIC to determine the relative efficacy and safety of vancomycin and daptomycin used at higher than traditional doses.

Conditions
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Bacteremia

Intervention / Treatment
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* Drug: Vancomycin
* Drug: Daptomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Signed informed consent All cases of suspected MRSA bacteremia as determined by a patient with at least one blood culture growing gram-positive cocci in clusters with a clinical syndrome consistent with true bacteremia including fever, hypothermia (temperature < 36.0º C), tachycardia (heart rate > 100 beats/minute), hypotension (systolic blood pressure < 90 mm Hg) or other clinical features of sepsis. All cases of right-sided native valve endocarditis due to MRSA Patients who are diagnosed with left-sided native valve endocarditis after randomization will be continued in the study Patients with MRSA bacteremia associated with infected foreign bodies, including vascular prostheses, orthopedic prostheses

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose vancomycin<br>Vancomycin dosed to achieve a trough of 15-20 microgram/mL. | Drug: Vancomycin<br>* Vancomycin dosed to achieve a trough of 15-20 microgram/mL.<br>|
| Experimental: High-dose daptomycin<br>Daptomycin dosed at 8 mg/kg/daily (every 48 hours in end-stage renal disease) | Drug: Daptomycin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Success at Test of Cure Visit. | Clinical success is the absence of treatment failures. Treatment failures will include death, clinical failure, microbiologic failure, or an adverse event requiring a change in therapy or discontinuation in therapy. | 30-42 days post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event Rate in Each Arm, Including the Nephrotoxicity and Skeletal Muscle Toxicity |  | 30-42 days post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methicillin-resistant, Staphylococcus aureus