Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia

Exclusion Criteria

• •Received \>48 hours of vancomycin therapy in the 7 days prior to enrollment;
• •Received any systemic antibacterial agents potentially effective against MRSA in the 7 days prior to enrollment;
• •Anticipated requirement of antibiotics potentially effective against MRSA;
• •High likelihood of left-sided infective endocarditis (LIE);
• •Known/suspected polymicrobial bacteremia or infection including Gram-negative infections;
• •Known pneumonia, osteomyelitis, or meningitis;
• •Intravascular foreign material unless material intended removed within 3 days;
• •Prosthetic heart valve;
• •Cardiac decompensation, valve damage, or both such that high likelihood of valve replacement surgery within first 3 days of study drug treatment;
• •Moribund clinical condition such that death likely within first 3 days of study drug treatment;
• •Shock or hypotension or oliguria unresponsive to fluids after 4 hours;
• •Received investigational drug within 30 days of study entry
• •Received statins or other therapy with associated with rhabdomyolysis within 2 days of study entry;
• •History of significant allergy or intolerance to vancomycin or daptomycin
• •Infecting pathogen with confirmed reduced susceptibility to vancomycin;
• •Infecting pathogen with confirmed reduced susceptibility to daptomycin
• •Creatinine clearance \<30 mL/min (Cockcroft-Gault equation actual body weight)
• •Serum creatine phosphokinase (CPK) ≥500 U/L
• •Alanine transaminase (ALT) or aspartate aminotransferase (AST) \>5 X ULN;
• •Total bilirubin ≥3.0 mg/dL;
• •Severe neutropenia or expected development severe neutropenia during study;
• •Known or suspected HIV infection with a CD4+ T-cell count \<200/μL;
• •Unlikely to comply with study procedures or return for evaluations;
• •Body Mass Index (BMI) ≥40 kg/m2;
• •Pregnant or nursing;
• •Female of childbearing potential not willing to practice barrier methods of birth control.
• •CONTINUATION CRITERIA:
• •Fulfills A or B or both: A) Confirmed complicated MRSA bacteremia B) Possible or definite RIE caused by MRSA according to modified Duke criteria;
• •Infecting S. aureus strain susceptible to vancomycin;
• •Infecting S. aureus strain susceptible to daptomycin;
• •Appropriate treatment of any foci of infection within first 3 days of study;