LL-37 vs Polymyxin B
Human cathelicidin-derived antimicrobial peptide (37 amino acids) that disrupts bacterial membranes at MIC 0.62 μM against S. aureus, neutralizes endotoxin (LPS) to prevent septic shock, and has reached Phase II clinical trials as Ropocamptide for wound healing — achieving 6-fold accelerated healing at 0.5 mg/mL in venous leg ulcers
Cyclic lipopeptide antibiotic from Paenibacillus polymyxa containing 10 amino acids with 6 diaminobutyric acid residues and a fatty acid tail — FDA-approved since 1964 as a last-resort treatment for multidrug-resistant Gram-negative infections including Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacteriaceae, targeting lipid A of bacterial lipopolysaccharide with rapid bactericidal membrane disruption
Written by Michael Carroll — Owner, Director of Research · Reviewed by the Peptide Initiative Research Team · Editorial standards
Quick comparison
Dose range
LL-37
1.6–1.6 mg/mL
Polymyxin B
1.25–1.5 mg/kg
Frequency
LL-37
Once daily
Polymyxin B
Multiple times daily
Administration
LL-37
Topical application (wound healing)
Polymyxin B
Intravenous infusion (on the FDA label)
Cycle length
LL-37
12+ weeks
Polymyxin B
7-14 days, infection-dependent — no source sets a fixed course
Onset speed
LL-37
Moderate (1-2 weeks)
Polymyxin B
Rapid (hours to days)
Evidence level
LL-37
Moderate human trials (Phase 1-2)
Polymyxin B
Strong human trials (Phase 3 or FDA approved)
Benefit ratings
Wound Healing
Fighting Infections
Immune Boost
Fighting Resistant Infections
Stopping Bacterial Toxins
Wound Protection
Compound specifications
LL-37
Molecular formula
C205H340N60O53
Molecular weight
4,493.26 Da
Half-life
Short systemic half-life (minutes) due to protease susceptibility; local tissue persistence at wound sites is longer due to binding to extracellular matrix components and lipid membranes
Bioavailability
Topical application achieves high local wound-bed concentrations; systemic bioavailability limited by rapid proteolytic degradation and serum protein binding; not intended for oral delivery
CAS number
154947-66-7
Polymyxin B
Molecular formula
C₅₆H₉₈N₁₆O₁₃ (polymyxin B₁ free base)
Molecular weight
1,203.5 g/mol (free base); ~1,385 g/mol (sulfate salt)
Half-life
Terminal half-life: 9-11.5 hours in patients with normal renal function; does not require renal dose adjustment (unlike colistimethate); achieves steady-state within 1-2 days with loading dose
Bioavailability
IV: 100% (direct administration); oral: negligible (not absorbed from GI tract — used topically in the gut for selective decontamination); inhaled: local pulmonary concentrations achieved with systemic absorption variable; topical: minimal systemic absorption
CAS number
1405-20-5 (polymyxin B sulfate)
Dosing compared
LL-37
Topical
0.5 mg/mL gel
Twice weekly · 4 weeks
Lowest dose in the LL-37 (ropocamptide) Phase I/IIa venous leg-ulcer trial and the most effective: ~6-fold faster healing and ~68% ulcer-area reduction vs placebo, applied to the wound twice weekly [4].
1.6 mg/mL gel
Twice weekly · 4 weeks
Mid dose in the same trial; ~3-fold improvement and ~50% area reduction vs placebo. The highest tested concentration (3.2 mg/mL) showed no benefit over placebo, so dose escalation above this is not supported [4].
Polymyxin B
Intravenous
Loading dose 2.0-2.5 mg/kg (20,000-25,000 units/kg)
Once on day 1 · Day 1 loading, then maintenance
The consensus loading dose for serious multidrug-resistant Gram-negative infection, by total body weight, infused over 1 hour [7]. It is not on the FDA label, which predates this guidance [6]. 1 mg of polymyxin B is 10,000 units — a dose quoted without saying which convention it uses cannot be interpreted [7].
1.25-1.5 mg/kg (12,500-15,000 units/kg) per dose
Every 12 hours · 7-14 days, infection-dependent
Consensus maintenance dosing, infused over 1 hour [7]. That works out to 2.5-3 mg/kg/day, or 25,000-30,000 units/kg/day — ABOVE the FDA label's stated maximum of 25,000 units/kg/day [6], which is one of the outdated-product-information problems the consensus panel was convened to resolve [7]. Unlike colistin, polymyxin B is not dose-reduced for renal impairment or dialysis [7]; the FDA label, written before that was understood, does instruct reduction in renal impairment [6]. This is a hospital drug given by clinicians who know which convention they are using.
Intramuscular
25,000-30,000 units/kg/day divided every 4-6 hours
Every 4-6 hours · Infection-dependent
FDA label intramuscular dosing; not generally recommended due to injection-site pain. [6]
Intrathecal
50,000 units once daily for 3-4 days, then 50,000 units every other day
Daily then every other day · At least 2 weeks after CSF cultures turn negative
FDA label intrathecal regimen for meningitis (adults and children >2 yr); typically given with concomitant IV polymyxin. Children <2 yr: 20,000 units/day for 3-4 days. [6]
Topical
10,000-25,000 units/mL solution, 1-3 drops
Hourly at first, lengthening the interval as the response allows · Until infection resolves
Topical and subconjunctival use for eye infections caused by susceptible Pseudomonas aeruginosa is on the FDA label [6]. The concentration is 0.1-0.25%, which is the same thing as 10,000-25,000 units per mL — written here in units because that is how the rest of this drug's dosing is expressed.
Best suited for
LL-37
Treatment of chronic non-healing wounds including venous leg ulcers and diabetic ulcers
LL-37 is particularly well-suited for individuals focused on treatment of chronic non-healing wounds including venous leg ulcers and diabetic ulcers. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Immune defense against antibiotic-resistant bacterial infections (MRSA, Pseudomonas)
LL-37 is particularly well-suited for individuals focused on immune defense against antibiotic-resistant bacterial infections (mrsa, pseudomonas). Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Anti-biofilm strategies for chronic wound infections and medical device-associated infections
LL-37 is particularly well-suited for individuals focused on anti-biofilm strategies for chronic wound infections and medical device-associated infections. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Boosting innate immune defense in immunocompromised or aging individuals
LL-37 is particularly well-suited for individuals focused on boosting innate immune defense in immunocompromised or aging individuals. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Polymyxin B
Treatment of life-threatening multidrug-resistant Gram-negative infections when carbapenems and other agents have failed
Polymyxin B is particularly well-suited for individuals focused on treatment of life-threatening multidrug-resistant gram-negative infections when carbapenems and other agents have failed. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Salvage therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections and pneumonia
Polymyxin B is particularly well-suited for individuals focused on salvage therapy for carbapenem-resistant acinetobacter baumannii (crab) bloodstream infections and pneumonia. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Intrathecal/intraventricular treatment of MDR Gram-negative meningitis and ventriculitis
Polymyxin B is particularly well-suited for individuals focused on intrathecal/intraventricular treatment of mdr gram-negative meningitis and ventriculitis. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Inhaled therapy for MDR Gram-negative ventilator-associated pneumonia (VAP) as adjunct to systemic therapy
Polymyxin B is particularly well-suited for individuals focused on inhaled therapy for mdr gram-negative ventilator-associated pneumonia (vap) as adjunct to systemic therapy. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Side effects
LL-37
Common
- Local site irritation
- Transient stinging or burning
- Mild perilesional erythema
- Increased wound exudate
Uncommon
- Allergic contact reaction
Serious
- Hemolytic activity at systemic concentrations
Polymyxin B
Common
- Nephrotoxicity
- Infusion-related histamine release
- Neurotoxicity
- Skin hyperpigmentation
Uncommon
- Neuromuscular blockade
Serious
- Acute kidney injury requiring dialysis
Safety & evidence
LL-37
Evidence level
Moderate human trials (Phase 1-2)
FDA status
Research compound
Safety overview
LL-37 is an endogenous cathelicidin antimicrobial peptide naturally produced by immune cells and epithelial tissues, conferring inherent biocompatibility and low toxicity at physiological concentrations. Synthetic LL-37 shows excellent safety in in vitro immune assays and animal models with no hepatotoxicity, nephrotoxicity, or genotoxicity at relevant doses. At elevated concentrations, the cationic amphipathic structure can cause hemolysis and cell membrane damage, but therapeutic doses are far below these thresholds. Injection site reactions are minimal in research applications.
Contraindications
- Known hypersensitivity to cathelicidin peptides or formulation components
- Active hemolytic conditions — LL-37 demonstrates concentration-dependent hemolytic activity
- Pregnancy and breastfeeding — insufficient reproductive safety data from clinical trials
- Severe renal impairment — peptide clearance may be altered
Polymyxin B
Evidence level
Strong human trials (Phase 3 or FDA approved)
FDA status
FDA approved. Indicated for acute infections caused by susceptible Pseudomonas aeruginosa (urinary tract, meninges, bloodstream), and for serious infections caused by H. influenzae, E. coli, Aerobacter aerogenes and Klebsiella pneumoniae when less toxic drugs are ineffective or contraindicated. Carries a BOXED WARNING. Meningeal infections must be treated by the intrathecal route only.
Safety overview
Polymyxin B carries a BOXED WARNING, and it is the most important thing on this page [6]. When given intramuscularly or intrathecally it is to be given only to hospitalised patients under constant physician supervision. Renal function must be determined before use and dosage reduced in renal damage; nephrotoxicity shows as albuminuria, cellular casts and azotemia, and falling urine output with a rising BUN is an instruction to stop the drug. Neurotoxic reactions present as irritability, weakness, drowsiness, ataxia, perioral paraesthesia, numbness of the extremities and blurred vision, usually with the high serum levels seen in renal impairment. Most seriously, the label states the neurotoxicity CAN RESULT IN RESPIRATORY PARALYSIS FROM NEUROMUSCULAR BLOCKADE, especially when given soon after anaesthesia or muscle relaxants. The boxed warning names the drugs to avoid concurrently or sequentially: bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, cephaloridine, paromomycin, viomycin and colistin. Safety in human pregnancy has not been established. Beyond the box, the label reports drug fever, urticarial rash, severe pain at intramuscular injection sites, thrombophlebitis at intravenous sites, and Clostridioides difficile associated diarrhoea ranging from mild to fatal colitis, which can begin more than two months after the antibiotic was given [6].
Contraindications
- Prior hypersensitivity reaction to polymyxins — the FDA label's only stated contraindication
- Concurrent or sequential use of other neurotoxic or nephrotoxic drugs, which the boxed warning names: bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, cephaloridine, paromomycin, viomycin and colistin
- Soon after anaesthesia or muscle relaxants — the boxed warning flags respiratory paralysis from neuromuscular blockade
- Pregnancy — the boxed warning states safety in human pregnancy has not been established
- Myasthenia gravis — neuromuscular blockade is the mechanism behind the label's respiratory-paralysis warning
Which is right for you?
Choose LL-37 if...
- Treatment of chronic non-healing wounds including venous leg ulcers and diabetic ulcers
- Immune defense against antibiotic-resistant bacterial infections (MRSA, Pseudomonas)
- Anti-biofilm strategies for chronic wound infections and medical device-associated infections
- Boosting innate immune defense in immunocompromised or aging individuals
Choose Polymyxin B if...
- Treatment of life-threatening multidrug-resistant Gram-negative infections when carbapenems and other agents have failed
- Salvage therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections and pneumonia
- Intrathecal/intraventricular treatment of MDR Gram-negative meningitis and ventriculitis
- Inhaled therapy for MDR Gram-negative ventilator-associated pneumonia (VAP) as adjunct to systemic therapy