The treatment of skin infections caused by Staphylococcus aureus is limited by acquired antibiotic resistance and poor drug delivery into pathogen and host cells. Here, we investigated the antibacterial activities of six topically used antimicrobials and a cationic polymer, polyhexamethylene biguanide (PHMB), against intracellular MSSA strain RN4420 and MRSA strains EMRSA-15 and USA 300.