Intervention: Daptomycin
Trial phase: Phase 4
ATC code: J01XX09
SMILES: CCCCCCCCCC(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(N)=O)C(=O)NC(CC(=O)O)C(=O)NC1C(=O)NCC(=O)NC(CCCN)C(=O)NC(CC(=O)O)C(=O)NC(C)C(=O)NC(CC(=O)O)C(=O)NCC(=O)NC(CO)C(=O)NC(C(C)CC(=O)O)C(=O)NC(CC(=O)c2ccccc2N)C(=O)OC1C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 5
Group description: Cohort 4. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 7 to 14 days based on disease resolution or Investigator discretion.
Eligibility criteria:
Inclusion Criteria:

Written informed consent
Male or female ≥18 years of age
Diagnosis of cSSSI or Staphylococcus aureus (S. aureus) bacteremia
Renal impairment of CLcr of 30 - 50 mL/min or CLcr <30 mL/min per Cockcroft-Gault equation using actual body weight
Functioning hemodialysis access and on stable regimen for those receiving dialysis
In appropriate health for the study with no acute or chronic illnesses that could adversely impact safety or ability to complete the study

Specific inclusion criteria for cSSSI:

Presence of a wound infection, major abscess, severe carbunculosis, infected ulcers, dialysis access site infection, or other type of infection in presence of complicating factor
At least 3 of the following symptoms, signs, or laboratory values of a skin infection: elevated temperature; elevated white blood cell (WBC) count; pain; tenderness; swelling; erythema greater than 1 centimeter (cm) beyond wound edge; induration; pus formation
Evidence of a Gram-positive infecting pathogen as indicated by positive Gram stain or culture obtained within 96 hours prior to study drug administration
Infection of sufficient severity to require parenteral antimicrobial therapy

Specific inclusion criteria for S. aureus bacteremia:

• Documented S. aureus bacteremia defined as at least one positive blood culture for S. aureus obtained within 96 hours prior to the first dose of study medication

Exclusion Criteria:

Pregnant or lactating females, or unwilling to practice barrier methods of birth control
Received an investigational drug (including experimental biologic agents) within 30 days of study entry
Unable to discontinue use of HMG-CoA reductase inhibitor therapy while on study
Known allergy or intolerance to daptomycin, penicillin, or vancomycin
Active intravenous (IV) drug abuse
Confirmed or suspected osteomyelitis, septic arthritis, meningitis, epidural abscess, intra-abdominal infection, pneumonia, or infective endocarditis
Required use of non-study systemic antibacterial agent with activity against target pathogen
History of muscular disease
Neurological disease except stroke >6 months prior to study entry
Intramuscular injection within 7 days of study drug administration
Moribund clinical condition (high likelihood of death during next 3 days)
Shock or hypotension (supine systolic blood pressure <80 millimeters of mercury [mmHg])
Body mass index (BMI) <18 or >40 kilograms per meter squared (kg/m^2) [BMI = weight (kg)/height (m^2)]
Known human immunodeficiency virus (HIV) infection with CD4 count ≤200 cells/millimeter (mm)^3
Neutropenic participants with an absolute neutrophil count ≤500 cells/mm^3
Anticipated to develop neutropenia absolute neutrophil count ≤500 due to prior or planned chemotherapy
Alanine aminotransferase (ALT) value >3 × upper limit of normal (ULN)
Aspartate aminotransferase (AST) value >3 × ULN
Total bilirubin values ≥ 1.5 x ULN associated with ALT values >3 x ULN
Creatine phosphokinase (CPK) value >2 × ULN
Hemoglobin <8 grams per deciliter (gm/dL)
Unlikely to comply with study procedures or to return for evaluations
History of rhabdomyolysis
Prior enrollment into this study
Infections caused by Gram-positive pathogens known to be resistant to daptomycin or selected comparator agent

Specific exclusion criteria for cSSSI:

Minor or superficial skin infections as the primary site of infection
Cellulitis or erysipelas not associated with complicating factor as primary site of infection
Perirectal abscess, hidradenitis suppurativa, concomitant gangrene, myositis, multiple infected ulcers at distant sites, necrotizing fasciitis, or infected third-degree burn wounds
Infections requiring emergency surgery
Infections suspected or documented to be due exclusively to gram-negative, anaerobic, or fungal organism
Confirmed or suspected disorder that could interfere with the evaluations (for example, primary skin disorders)
Use of a topical antibiotic at the site of the infection
Use of systemic antibacterial therapy for the infection for >24 hours within 48 hours prior to start of study drug unless (a) infecting Gram-positive pathogen resistant to therapy or (b) therapy administered for 3 or more days with worsening or no improvement
Planned surgical treatment that is considered curative of the infection

Specific exclusion criteria for S. aureus bacteremia:

Has intravascular foreign material at the time the positive blood culture was drawn (for example., intracardiac pacemaker wires, percutaneous or implanted venous catheters, vascular grafts) unless material removed within 4 days after first dose of study medication or approval of medical monitor (exceptions: vascular stents in place for >6 months, permanent pacemaker attached via epicardial leads, or any dialysis access device unless this material is felt to be infected)
Prosthetic heart valve
Cardiac decompensation or valve damage or both with high likelihood of valve surgery in the 3 days after randomization
Polymicrobial blood infection