The present invention describes method of treating bacterial infections, including MRSA. In various embodiments, the methods can use interferon beta, which is found to have antimicrobial activity. In certain embodiments, the interferon beta can be human interferon beta. In other embodiments, the interferon beta can be mouse interferon beta. In further embodiments, the interferon beta can be human interferon beta containing amino acid substitutions to make the human interferon beta more cationic in neutral pH.