NisinvsDaptomycin

Molecular Formula

C₁₄₃H₂₃₀N₄₂O₃₇S₇

Molecular Weight

3,354.12 Da

Half-Life

Rapidly degraded in GI tract by digestive proteases; stable for hours to days in food matrices at acidic pH; lanthionine ring structures resist most environmental proteases; thermostable (survives pasteurization)

Bioavailability

Degraded by pancreatic proteases in GI tract (does not affect gut microbiome at dietary levels); topical application achieves effective local concentrations; optimal activity at pH 2-6; lanthionine bridges provide significant protease resistance compared to linear peptides

CAS Number

1414-45-5

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

Common

• No significant effects at dietary levels
• Mild GI discomfort at research doses
• Local irritation (topical use)

Uncommon

• Milk protein allergic reaction
• Gram-negative overgrowth

Serious

• No documented serious adverse effects

Common

• CPK elevation
• GI effects (nausea, diarrhea, vomiting)
• Headache and insomnia
• Injection site reactions

Uncommon

• Eosinophilic pneumonia

Serious

• Rhabdomyolysis

Evidence Level

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Nisin holds FDA GRAS status since 1988 with over 50 years of documented safe human consumption, making it the only antimicrobial peptide with this comprehensive long-term safety record. Oral LD50 of 174 mg/kg in mice (comparable to table salt) demonstrates extraordinary safety margin. Acceptable daily intake established at 0.13 mg/kg body weight with no reported serious adverse events at this or higher levels. Primary risk is milk protein contamination during production, requiring screening for lactose-intolerant or milk-allergic individuals.

Contraindications

• xKnown hypersensitivity to nisin or Lactococcus lactis-derived products
• xMilk protein allergy — nisin production involves dairy-associated bacteria and preparations may contain trace milk proteins
• xPregnancy and breastfeeding at therapeutic (non-dietary) doses — standard dietary exposure through preserved foods is considered safe
• xActive inflammatory bowel disease — potential for local irritation at high oral concentrations exceeding normal dietary levels

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