The present invention is directed to compositions and methods for preventing and/or treating diseases and disorders of patients caused by non-Staphylococcal microorganisms. In particular, compositions and methods contain lysostaphin, altered forms of lysostaphin as compared to wild-type, and synergistic combinations of lysostaphin plus additional conventional treatments such as other enzyme, antibiotic and/or antibody treatment. The invention is also directed to detecting and identifying altered forms of lysostaphin that possess increased efficacy against infections as compared to wild-type lysostaphin, and forms that generate a minimal or no immune response in a patient. The invention is also directed to method of manufacturing lysostaphin and altered forms of lysostaphin, and compositions that direct the lysostaphin to the site of the infection such as aerosolized nanoparticles.