OBJECTIVES: Staphylococcus aureus colonization of the skin and the nostrils remains a major cause of surgical-site infections despite preoperative and preventive procedures. To date, many compounds have been used for S. aureus decolonization, including mupirocin ointments and antiseptics, with variable results. The emergence of mupirocin-resistant S. aureus strains has led to the search for new antimicrobial agents specifically for S. aureus decolonization. In this work we evaluated squalamine and related parent-derived ointments (1%) as potential new compounds for S. aureus decolonization in a new mouse model. METHODS: We report the development and application of squalamine and related parent-derived ointments in a new mouse skin model. After skin shaving, mice were colonized with an S. aureus suspension that was calibrated to 10⁴-10⁶ cfu/mL. The remaining bacterial load was monitored for 2 days after a single application of squalamine by spreading. RESULTS: We found that S. aureus colonization of the skin was stable for at least 2 days before it was naturally eliminated. Using this model we found that squalamine ointment (1%) could reduce S. aureus viable cells by up to 4 log with a single, 1 h application of ointment, whereas mupirocin application reduced viable cell numbers by only 1.3 log during that same time (P < 0.05). CONCLUSIONS: Our results suggest that such compounds may be useful for S. aureus nasal and skin decolonization and may constitute a potent alternative for skin and nasal antisepsis before surgery.
OBJECTIVES:Staphylococcus aureus colonization of the skin and the nostrils remains a major cause of surgical-site infections despite preoperative and preventive procedures. To date, many compounds have been used for S. aureus decolonization, including mupirocin ointments and antiseptics, with variable results. The emergence of mupirocin-resistant S. aureus strains has led to the search for new antimicrobial agents specifically for S. aureus decolonization. In this work we evaluated squalamine and related parent-derived ointments (1%) as potential new compounds for S. aureus decolonization in a new mouse model. METHODS: We report the development and application of squalamine and related parent-derived ointments in a new mouse skin model. After skin shaving, mice were colonized with an S. aureus suspension that was calibrated to 10⁴-10⁶ cfu/mL. The remaining bacterial load was monitored for 2 days after a single application of squalamine by spreading. RESULTS: We found that S. aureus colonization of the skin was stable for at least 2 days before it was naturally eliminated. Using this model we found that squalamine ointment (1%) could reduce S. aureus viable cells by up to 4 log with a single, 1 h application of ointment, whereas mupirocin application reduced viable cell numbers by only 1.3 log during that same time (P < 0.05). CONCLUSIONS: Our results suggest that such compounds may be useful for S. aureus nasal and skin decolonization and may constitute a potent alternative for skin and nasal antisepsis before surgery.
Authors: Bo Wang; Boobalan Pachaiyappan; Jordon D Gruber; Michael G Schmidt; Yong-Mei Zhang; Patrick M Woster Journal: J Med Chem Date: 2016-03-28 Impact factor: 7.446