Genomic and Phenotypic Characterization of Mupirocin-resistant Staphylococcus aureus Clinical Isolates

Colonization with Staphylococcus aureus is a risk factor for subsequent infection. Decolonization with the topical antibiotic mupirocin is effective and reduces the risk of subsequent S. aureus infection for both methicillin-sensitive and methicillin-resistant (MRSA) strains but may select for mupirocin-resistant isolates.

We characterized oxacillin and mupirocin susceptibility amongst 384 S. aureus strains isolated from clinical samples isolated in 2017-2023 in Tampa, Florida, spanning strains collected before and after the onset of the coronavirus disease 2019 (COVID-19) pandemic. Whole genome sequencing of bacterial isolates was conducted in parallel and correlated with drug susceptibility profiles.

Mupirocin resistance (MupR) was nearly exclusively present in MRSA strains (103/106, 97.1% of MupR; 103/299, 34.4% of MRSA). Although our hospital protocol for decolonization shifted to povidone iodine in the post-COVID period, the overall prevalence of MupR did not change in pre-COVID and post-COVID samples (28.9% vs 26%). Genotype correlated with antibiotic susceptibility with low-level MupR, linked to mutations in ileS and high-level MupR, linked to the presence of mupA. Genome analysis revealed that most MupR strains fell into 3 sequence types (ST) falling into 2 major clonal complexes (CC): CC8 ST8 (including community-associated MRSA strains USA300 and USA500), CC5 ST5 (associated with healthcare-associated MRSA such as USA100), and CC5 ST3390. ST3390 isolates had the highest prevalence of MupR (30/36 83%; high-level MupR 20/36 55.6%; low-level MupR 10/36 27.8%).

Mupirocin resistance was prevalent in our hospital MRSA strains. We also found evidence for emergence and persistence of ST3390 MRSA-MupR strains in Florida.