Eradication of meticillin-resistant Staphylococcus aureus from human skin by the novel LL-37-derived peptide P10 in four pharmaceutical ointments

Int J Antimicrob Agents. 2019 Nov;54(5):610-618. doi: 10.1016/j.ijantimicag.2019.07.014. Epub 2019 Jul 26.

Abstract

Skin bacterial colonization/infection is a frequent cause of morbidity in patients with chronic wounds and allergic/inflammatory skin diseases. This study aimed to develop a novel approach to eradicate meticillin-resistant Staphylococcus aureus (MRSA) from human skin. To achieve this, the stability and antibacterial activity of the novel LL-37-derived peptide P10 in four ointments was compared. Results indicate that P10 is chemically stable and antibacterial in hypromellose gel and Softisan-containing cream, but not in Cetomacrogol cream (with or without Vaseline), at 4 °C for 16 months. Reduction in MRSA counts on Leiden human epidermal models (LEMs) by P10 in hypromellose gel was greater than that of the peptide in Cetomacrogol cream or phosphate buffered saline. P10 did not show adverse effects on LEMs irrespective of the ointment used, while Cetomacrogol with Vaseline and Softisan cream, but not hypromellose gel or Cetomacrogol cream, destroyed MRSA-colonized LEMs. Taking all this into account, P10 in hypromellose gel dose-dependently reduced MRSA colonizing the stratum corneum of the epidermis as well as biofilms of this bacterial strain on LEMs. Moreover, P10 dose-dependently reduced MRSA counts on ex-vivo human skin, with P10 in hypromellose gel being more effective than P10 in Cetomacrogol and Softisan creams. P10 in hypromellose gel is a strong candidate for eradication of MRSA from human skin.

Keywords: Antimicrobial peptides; Biofilm; MRSA; Release profile; Skin; Stability study; Topical ointments.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Topical
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Cetomacrogol / pharmacology
  • Drug Carriers / pharmacology
  • Humans
  • Hypromellose Derivatives / pharmacology
  • Lipids / pharmacology
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Ointments / pharmacology*
  • Petrolatum / pharmacology
  • Skin / microbiology
  • Staphylococcal Skin Infections / drug therapy*

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Drug Carriers
  • Lipids
  • Ointments
  • ropocamptide
  • Hypromellose Derivatives
  • Petrolatum
  • Cetomacrogol
  • softisan 100