Clinical relevance of mupirocin resistance in Staphylococcus aureus

SummaryMupirocin is a topical antibiotic used for decolonization of meticillin-susceptible S. aureus (MSSA) and meticillin-resistant S. aureus (MRSA), both in patients and in healthcare personnel, and for treatment of local skin and soft tissue infections caused by S. aureus and streptococcal species. Mupirocin prevents bacterial protein synthesis by inhibiting the bacterial isoleucyl-tRNA synthetase (IleRS). Low-level resistance against mupirocin, defined as minimum inhibitory concentration (MIC) of 8–256 mg/L, results from a point mutation in the native IleRS, and high-level resistance (MIC ≥512 mg/L) is mediated by the mupA (ileS-2) gene, located on mobile genetic elements decoding for an alternate IleRS. EUCAST and BSAC clinical thresholds for S. aureus are ≤1 mg/L for susceptible and >256 mg/L for resistant, placing the susceptible threshold at the epidemiological cut-off value (ECOFF). Isolates with MICs above the wild type (ECOFF 1 mg/L) but without a recognized resistance mechanism (MIC ≤4 mg/L) will thus be reported intermediate. Resistance to mupirocin, both high- and low-level, reduces the effectiveness of decolonizing strategies for S. aureus or MRSA. Low-level resistant isolates may initially be eradicated as effectively as susceptible isolates, but recolonization appears to be more usual. Increased use of mupirocin has been associated with emergence of resistance through enhanced selective pressure and cross-transmission. Unrestricted over-the-counter use and treatment of wounds and pressure sores with mupirocin are especially strongly associated with resistance. Yet emergence of mupirocin resistance following increased use has not been reported consistently, and an integrated understanding of all factors underlying the dynamics of mupirocin resistance in hospitals and communities is lacking.