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 (MSSA) 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 2017-2023 in Tampa, Florida, spanning strains collected before and after the onset of the 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 (MupLR), linked to mutations in ileS and high level MupR (MupHR), linked to the presence of mupA . Genome analysis revealed that most MupR strains fell into three sequence types (ST) falling into two 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%; MupHR 20/36 55.6%; MupLR 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.

In a survey of clinical isolates in Florida, 34.4% of MRSA strains were mupirocin resistant. Mupirocin resistance correlated with mutations in ileS or carriage of mupA . We found evidence for emergence of MRSA mupirocin-resistant strains that were sequence type ST3390.