Methicillin: A semisynthetic penicillin-related antibiotic, also known as Staphcillin, that once was effective against staphylococci (staph) resistant to penicillin because they produce the enzyme penicillinase. Rarely used now, methicillin has been largely superceded by Vancomycin. Over the past 50 years, staph bacteria have become resistant to various antibiotics, including the commonly used penicillin-related antibiotics, including methicillin. These resistant bacteria are called methicillin-resistant Staphylococcus aureus, or MRSA.