Mupirocin (formerly pseudomonic acid) is a naturally occurring antibiotic produced by Pseudomonas fluorescens active against most gram-positive cocci, including methicillin-sensitive and methicillin-resistant S aureus and most streptococci (but not enterococci). Used topically, it is somewhat effective in eliminating staphylococcal nasal carriage in the majority of patients for up to 3 months after application to the anterior nares twice daily for 5 days. However, recurrent colonization occurs (50% at the end of 1 year), and when mupirocin is used long-term over months, resistance can emerge. High rates of mupirocin resistance have been observed in methicillin-resistant S aureus isolates from surgical intensive care unit patients, despite minimal in-hospital mupirocin use. This finding suggests the benefit of mupirocin is limited. Monthly application for 5 days each month for up to a year decreases staphylococcal colonization, which in turn lowers the risk of recurrent staphylococcal skin infections. Studies demonstrate an associated reduction in postoperative staphylococcal lung infections in colonized patients treated with mupirocin. Whether it is more effective than trimethoprim-sulfamethoxazole or dicloxacillin plus rifampin for eradication of staphylococcal nasal carriage is unknown. The Infectious Diseases Society of America recommends the use of mupirocin with chlorhexidine preferentially over oral antibacterials for methicillin-resistant S aureus decolonization. Mupirocin appears to be equal to oral -lactams in the treatment of mild impetigo.