The invention generally relates to compositions and methods for preventing sternal wound infections, such as mediastinitis. In certain embodiments, the invention provides an antimicrobial composition including at least one bioresorbable polymer, such as a tyrosine-derived polyesteramide, and at least one antimicrobial agent, in which the composition is adapted to be topically applied to an esophageal perforation in a subject or a median sternotomy incision site in the subject, and in which the at least one antimicrobial agent is present in an amount effective to inhibit development of mediastinitis in the subject.