Peptide Comparison
DaptomycinvsGramicidin
Cyclic lipodepsipeptide antibiotic containing 13 amino acids and a decanoyl lipid tail from Streptomyces roseosporus — FDA-approved as Cubicin for complicated skin infections (2003) and S. aureus bacteremia including right-sided endocarditis (2006), operating through calcium-dependent phosphatidylglycerol-specific membrane depolarization with rapid bactericidal activity against MRSA, VRE, and other multidrug-resistant Gram-positive pathogens
Historic 15-amino-acid linear pentadecapeptide antibiotic with alternating D- and L-amino acids — the first commercially produced antibiotic discovered by René Dubos in 1939, forming monovalent cation-selective transmembrane channels in bacterial membranes, FDA-approved as a topical/ophthalmic antimicrobial component of Neosporin and related preparations
At a Glance
Quick
comparison
Dose Range
Daptomycin
4–6 mg/kg
Gramicidin
0.025–0.25 mg/mL
Frequency
Daptomycin
Once daily
Gramicidin
Multiple times daily
Administration
Daptomycin
Intravenous infusion over 30 minutes (FDA-approved)
Gramicidin
Topical application (primary clinical route)
Cycle Length
Daptomycin
4-6 weeks
Gramicidin
8-12 weeks
Onset Speed
Daptomycin
Rapid (hours to days)
Gramicidin
Rapid (hours to days)
Evidence Level
Daptomycin
Strong human trials (Phase 3 or FDA approved)
Gramicidin
Strong human trials (Phase 3 or FDA approved)
Efficacy
Benefit
ratings
Immune
Energy
Technical Data
Compound
specifications
Daptomycin
Molecular Formula
C₇₂H₁₀₁N₁₇O₂₆
Molecular Weight
1,620.69 Da
Half-Life
Terminal half-life: 8-9 hours in healthy adults with normal renal function; supports once-daily dosing; post-antibiotic effect: 1-6 hours against S. aureus; renal dose adjustment: CrCl <30 mL/min — extend interval to every 48 hours
Bioavailability
IV: 100% (direct administration); not orally bioavailable (degraded in GI tract); inactivated in lungs by pulmonary surfactant
CAS Number
103060-53-3
Gramicidin
Molecular Formula
C₉₉H₁₄₀N₂₀O₁₇ (gramicidin A)
Molecular Weight
1,882.3 Da (gramicidin A); Gramicidin D mixture: ~1,880-1,900 Da average
Half-Life
Local tissue persistence: hours to days at topical application sites (protease-resistant D-amino acid structure); systemic half-life: not applicable (hemolytic — never administered systemically); single channel lifetime: ~1 second (open/close kinetics in electrophysiology)
Bioavailability
Topical: local tissue concentrations at application site; systemic absorption negligible through intact skin and eye; oral bioavailability: not applicable (not used orally for systemic effect; would cause GI hemolysis); intrinsically resistant to proteases due to D-amino acid content
CAS Number
11029-61-1 (gramicidin A); 1405-97-6 (gramicidin D mixture)
Protocols
Dosing
tiers
Daptomycin
Gramicidin
Applications
Best
suited for
Daptomycin
Treatment of MRSA bacteremia and right-sided infective endocarditis (FDA-approved indication at 6 mg/kg)
Daptomycin is particularly well-suited for individuals focused on treatment of mrsa bacteremia and right-sided infective endocarditis (fda-approved indication at 6 mg/kg). Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Complicated skin and skin structure infections including surgical site infections and diabetic foot infections (FDA-approved at 4 mg/kg)
Daptomycin is particularly well-suited for individuals focused on complicated skin and skin structure infections including surgical site infections and diabetic foot infections (fda-approved at 4 mg/kg). Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
VRE bloodstream infections and endocarditis when ampicillin-based therapy is not feasible
Daptomycin is particularly well-suited for individuals focused on vre bloodstream infections and endocarditis when ampicillin-based therapy is not feasible. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Outpatient parenteral antibiotic therapy (OPAT) for Gram-positive infections requiring IV treatment
Daptomycin is particularly well-suited for individuals focused on outpatient parenteral antibiotic therapy (opat) for gram-positive infections requiring iv treatment. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Gramicidin
Topical treatment of bacterial conjunctivitis and external eye infections (FDA-approved)
Gramicidin is particularly well-suited for individuals focused on topical treatment of bacterial conjunctivitis and external eye infections (fda-approved). Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Prophylaxis and treatment of superficial skin infections, minor cuts, scrapes, and burns (OTC topical preparations)
Gramicidin is particularly well-suited for individuals focused on prophylaxis and treatment of superficial skin infections, minor cuts, scrapes, and burns (otc topical preparations). Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Research into ion channel biophysics, single-channel electrophysiology, and membrane transport mechanisms
Gramicidin is particularly well-suited for individuals focused on research into ion channel biophysics, single-channel electrophysiology, and membrane transport mechanisms. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Combination topical antimicrobial therapy providing Gram-positive coverage alongside polymyxin B for Gram-negatives
Gramicidin is particularly well-suited for individuals focused on combination topical antimicrobial therapy providing gram-positive coverage alongside polymyxin b for gram-negatives. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Safety Profile
Side
effects
Daptomycin
Common
- CPK elevation
- GI effects (nausea, diarrhea, vomiting)
- Headache and insomnia
- Injection site reactions
Uncommon
- Eosinophilic pneumonia
Serious
- Rhabdomyolysis
Gramicidin
Common
- Ophthalmic stinging/burning
- Local skin irritation
- Temporary blurred vision
- Contact sensitization
Uncommon
- Superinfection
Serious
- Hemolytic toxicity with systemic absorption
Research Status
Safety
& evidence
Daptomycin
Evidence Level
Strong human trials (Phase 3 or FDA approved)
FDA Status
FDA approved for this use
Safety Overview
Daptomycin is an FDA-approved antibiotic with extensive clinical safety data from Phase 2/3 trials and post-market pharmacovigilance spanning over 20 years. Key safety concerns include muscle toxicity (creatine phosphokinase elevation) occurring in 3-12% of treated patients, potentially progressing to myopathy with weakness if unmonitored. Pulmonary toxicity (eosinophilic pneumonia) is rare (<1%) but serious. Peripheral neuropathy, nausea, and injection site reactions are common but usually mild. Creatinine elevation in renal impairment is significant—dosing must be reduced in patients with eGFR <30 mL/min. CPK monitoring is essential during treatment, especially in patients on statins or with baseline elevations.
Contraindications
- xKnown hypersensitivity to daptomycin or any component of the formulation
- xPneumonia or any lower respiratory tract infection — daptomycin is inactivated by pulmonary surfactant (phosphatidylcholine) and will fail to treat pneumonia
- xConcurrent use of HMG-CoA reductase inhibitors (statins) is relatively contraindicated — consider temporary discontinuation to reduce risk of additive myotoxicity
- xPre-existing significant skeletal muscle disease or unexplained CPK elevation >5x ULN
Gramicidin
Evidence Level
Strong human trials (Phase 3 or FDA approved)
FDA Status
FDA approved for this use
Safety Overview
Gramicidin is a cyclic peptide antibiotic derived from Bacillus brevis with a 70+ year track record of topical safety. It functions as a pore-former in bacterial membranes and shows minimal systemic absorption when applied to intact skin or mucous membranes, making it extremely low-toxicity for localized use. The primary safety concern is sensitization reactions in 1-5% of users with prolonged exposure, not organ toxicity. Gramicidin is FDA-approved for topical antibacterial applications and generally well-tolerated across age groups.
Contraindications
- xKnown hypersensitivity to gramicidin or any component of topical/ophthalmic formulations
- xSystemic administration by any route — gramicidin is hemolytic and toxic to red blood cells; strictly topical/ophthalmic use only
- xDeep puncture wounds or severe burns requiring systemic antimicrobial coverage
- xProlonged use on large open wounds — even topical gramicidin may cause hemolysis if absorbed systemically through extensive denuded skin
Decision Guide
Which is
right for you?
Choose Daptomycin if...
- Treatment of MRSA bacteremia and right-sided infective endocarditis (FDA-approved indication at 6 mg/kg)
- Complicated skin and skin structure infections including surgical site infections and diabetic foot infections (FDA-approved at 4 mg/kg)
- VRE bloodstream infections and endocarditis when ampicillin-based therapy is not feasible
- Outpatient parenteral antibiotic therapy (OPAT) for Gram-positive infections requiring IV treatment
Choose Gramicidin if...
- Topical treatment of bacterial conjunctivitis and external eye infections (FDA-approved)
- Prophylaxis and treatment of superficial skin infections, minor cuts, scrapes, and burns (OTC topical preparations)
- Research into ion channel biophysics, single-channel electrophysiology, and membrane transport mechanisms
- Combination topical antimicrobial therapy providing Gram-positive coverage alongside polymyxin B for Gram-negatives