Fourteen mupirocin-resistant Staphylococcus aureus strains were isolated over 18 months; 12 exhibited low-level resistance, while two showed high-level resistance. Highly mupirocin-resistant strains contained a large plasmid which transferred mupirocin resistance to other S. aureus strains and to Staphylococcus epidermidis. This plasmid and pAM899-l, a self-transferable gentamicin resistance plasmid, have molecular and biologic similarities.Mupirocin is a topical antibiotic with excellent antistaphylococcal and antistreptococcal activity (3). It has been used to eradicate staphylococcal carriage in health care workers and patients (2,4,10,11,18,20,24). With increased use of mupirocin, especially with chronic use, resistance in Staphylococcus aureus has emerged (1,5,7,11,12,16,17,20,22,25). Of most concern is high-level mupirocin resistance, reported initially from England (5, 16,17,22) and now from the United States (11) and associated with clinical failure (11,16,22).In our long-term-care facility, we used mupirocin ointment in nares and wounds from June 1990 to December 1991 in an attempt to eradicate methicillin-resistant S. aureus from chronically colonized residents (11). This paper describes the emergence of mupirocin resistance in this setting, characterizes the mupirocin-resistant strains, and shows evidence for plasmid-mediated transfer of this resistance. This plasmid is further characterized by comparison with pAM899-1, a well-described conjugative plasmid.Fourteen mupirocin-resistant S. aureus strains were isolated from clinical specimens collected between June 1990 and December 1991 (11). Antibiotic susceptibilities were determined by Kirby-Bauer disc diffusion (14). Methicillin resistance was determined by growth after 24 h at 35°C on plates containing Mueller-Hinton agar (Difco, Inc., Detroit, Mich.) containing 6 ,ug of oxacillin (Sigma, St. Louis, Mo.) per ml and 4% sodium chloride (23). Fusidic acid susceptibility was determined by using growth on brain heart infusion agar (Difco) containing 25 p,g of fusidic acid per ml. Mupirocin MICs were determined by a microdilution method (9); a macrodilution assay with Mueller-Hinton broth was used to determine MICs of > 100 ,ug of mupirocin per ml.Transferability of mupirocin resistance was examined by filter matings as previously described by Forbes and Schaberg (8 made by using appropriate selective antibiotic-containing media. Additional mating experiments attempted to transfer high-level mupirocin resistance from LZ-1/879R4 (first-generation transconjugant, Mupr) to S. aureus SA-136 containing the gentamicin resistance plasmid, pAM899-1, to determine compatibility between these two self-transferable elements. Selective antibiotic media allowed the examination of the transfer of gentamicin resistance to the mupirocin-resistant strain in the same mating.DNA was isolated from S. aureus strains by the method described by Macrina et al. (13) and modified by Forbes and Schaberg (8). DNA was electrophoresed through 0.7% agarose (Bethesda Research Laboratori...
