The present invention relates to antimicrobial deoxyribonuclease-based compositions that inhibit growth and proliferation of Staphylococcus aureus bacteria. The present invention also relates to methods of administering the compositions in the treatment and prevention of S. aureus infections. The present invention also relates to methods of administering the compositions in the eradication of S. aureus nasal carriage, in order to prevent the transmission of S. aureus bacteria