Topical peptide spray outperforms placebo in healing burn wounds

Burn wound infections remain a major global health burden, often requiring hospitalization and delaying tissue repair. Topical antibiotics are widely used, but their overuse can disrupt the skin microbiome and drive antimicrobial resistance. Antimicrobial peptides (AMPs) offer a different approach: they disrupt microbial membranes through non-specific mechanisms, giving them broad-spectrum activity and a lower likelihood of resistance. Peceleganan (PL-5) is a synthetic α-helical AMP with 26 amino acid residues, designed to target wound pathogens. Earlier trials suggested it outperformed silver sulfadiazine (SSD) cream, but a placebo-controlled evaluation in burn wound infections was still needed. Given these challenges, further research into novel, placebo-controlled topical antimicrobial strategies for burn wound infections is needed.

The trial was led by researchers at the First Affiliated Hospital of Shenzhen University/Shenzhen Second People's Hospital and conducted across 23 centers in China. It was published (DOI: 10.1093/burns/tkaf064) on 06 October 2026 in Burns & Trauma. The phase IIIb trial randomized 348 adults with mild infected burn wounds to 2‰ PL-5 (peceleganan) spray or placebo once daily for 14 days. It assessed complete healing, bacterial clearance, overall efficacy, safety, and drug absorption. The primary endpoint was complete wound healing on day 15.

The trial enrolled 348 patients and randomly assigned 232 to PL-5 and 116 to placebo in a 2:1 ratio. Eligible participants were 18-65 years old, had mild burn infections covering no more than 10% of total body surface area (TBSA), and had test wounds of 25-100 cm² with positive bacterial cultures. Treatment was applied once daily for 14 days. On day 15, complete wound healing was 64.3% with PL-5 versus 43.1% with placebo (P = 0.0002), an absolute risk difference (ARD) of 21.2% and a number needed to treat (NNT) of 5. By day 21, healing reached 73.5% versus 56.9% (P = 0.0018). On day 15, microbiological efficacy was 72.3% versus 50.5% (P = 0.0001), and comprehensive efficacy was 63.1% versus 41.9% (P = 0.0003). Day 8 differences were not significant. Minimum inhibitory concentration (MIC) testing showed PL-5 inhibited nine common wound pathogens at a geometric mean MIC ≤ 9.110 μg/mL (MIC₅₀ 2-8 μg/mL; MIC₉₀ 2-16 μg/mL). PL-5 was active against common pathogens, including Staphylococcus epidermidis and Staphylococcus aureus. The PL-5 group showed better microbiological efficacy than placebo against both Staphylococcus epidermidis and Staphylococcus aureus. Pharmacokinetic sampling found blood concentrations below the lower limit of quantification (BQL), indicating no systemic absorption. Adverse events were similar between groups, with no drug-related serious adverse events (SAEs) and no deaths.

The authors said the trial was designed to test whether a topical antimicrobial peptide could speed wound closure without entering the bloodstream. They said PL-5's membrane-disrupting mechanism may help address antibiotic resistance, and the day-15 healing advantage over placebo was clinically meaningful. They added that the low adverse-event rates and undetectable plasma concentrations support further evaluation in broader wound-care settings. They said the results do not yet justify replacing standard care in all burn patients, but they support PL-5 as a promising local option for mild infections.

If approved, PL-5 topical spray could offer a locally acting, antibiotic-sparing option for mild burn wound infections, potentially reducing reliance on systemic or broad-spectrum antibiotics. Its lack of systemic absorption may be especially useful in outpatient or ward-based wound care, where repeated dressing changes are common. However, the trial focused on mild infections, excluded some patients with comorbidities, and followed patients for only 15 days after treatment. Longer studies are needed to assess recurrence, resistance, and effectiveness in surgical, chronic, and severe burn wounds. The authors say future phase IV research will test broader patient populations. For now, PL-5 remains an investigational therapy. Its role in standard burn care will depend on confirmatory studies and regulatory review.