Squalamine ointment for Staphylococcus aureus skin decolonization in a mouse model

• Published in: Journal of antimicrobial chemotherapy Vol. 66; no. 6; pp. 1306 - 1310
• Main Authors: DJOUHRI-BOUKTAB, Lamia, ALHANOUT, Kamel, ANDRIEU, Veronique, RAOULT, Didier, MARC ROLAIN, Jean, BRUNEL, Jean Michel
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2011; Oxford Publishing Limited (England)
• Subjects: Administration, Topical; Animals; Anti-Bacterial Agents - administration & dosage; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Bacterial Load; Biological and medical sciences; Cells; Cholestanols - administration & dosage; Drug resistance; Female; Human bacterial diseases; Humans; Infectious diseases; Medical sciences; Mice; Models, Animal; Ointments - administration & dosage; Pharmacology. Drug treatments; Rodents; Sepsis; Skin; Skin - microbiology; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - isolation & purification; Staphylococcus infections; Antineoplastic agent; Animal model; Rodentia; Ointment; Infection; Vertebrata; Squalamine; Mammalia; S. aureus; Mouse; mouse skin model; Bacteriosis; Dosage form; Bacteria; Micrococcales; Micrococcaceae; Skin; Staphylococcal infection; aminosterol derivatives; Staphylococcus aureus
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkr114

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. 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. 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). 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.