Increasing prevalence of a mupirocin- and fusidic acid-resistant MSSA CC121-t1994 clone in pediatric skin and soft tissue infections: 8-year longitudinal study at an Spanish Hospital

Introduction Skin and soft tissue infections (SSTI) in pediatric patients have increased in recent years, and mupirocin and fusidic acid are important therapeutic options. Materials and methods All 217 Staphylococcus aureus isolates recovered from pediatric SSTIs in a Spanish hospital during January 2018-october 2025 were characterized (one isolate/patient). The phenotypes and genotypes of antimicrobial resistance, virulence genes and genetic lineages were analyzed along three time periods (2018–2021, 2022–2023 and 2024–2025). Results Most of 217 isolates were methicillin-susceptible (MSSA, 91.2%), and these MSSA belonged to 14 clonal-complexes (CC), being CC121 (54.5%) the most prevalent followed by CC30 (11.6%) and CC45 (7.1%). Ten spa -types were found among MSSA-CC121 isolates, being t1994 predominant (75.0%), followed by t1077 and t272. Seventeen of the 19 MRSA isolates identified belonged to the lineages CC8, CC30, and CC5. Most of MSSA-CC121 isolates carried eta and/or etb (98/108, 90.7%), and this prevalence was even higher among CC121-t1994 isolates (93.8%). The tst gene was mainly detected among MSSA-CC30/CC22. The prevalence of MSSA-CC121 isolates increased during the 8-year study (21.6%/2018–2021, 50.6%/2022–2023, 65.2%/2024–2025), associated with an enrichment of spa -t1994 (9.8%/2018–2021, 59.6%/2024–2025), and a decrease in CC30 prevalence. High frequencies of mupirocin-resistant (MUP R , mostly mediated by mupA ) and fusidic-acid-resistant (FA R , mostly mediated by fusB ) were observed among S. aureus (43.8 and 30.9%, respectively), and resistance to both (MUP R -FA R ) was found in 29.5% of isolates, most of them MSSA-CC121 (95.3%). A significant increase in the rate of MUP R -FA R isolates was observed along the years, both among S. aureus (5.9%/2018–2021, 28.6%/2022–2023 and 43.8%/2024–2025) and CC121 isolates (27.3%/2018–2021, 53.8%/2022–2023 and 63.8%/2024–2025) ( p < 0.05). The prevalence of impetigo cases among the pediatric SSTIs increased along the years (2018–2021: 37.3%; 2022–2023: 68.8%; 2024–2025: 80.9%); in addition, a significant increase was observed in the prevalence of MSSA-CC121 and MSSA-CC121-MUP R -FA R in impetigo cases along the years ( p < 0.05). Conclusion a MUP R -FA R MSSA-CC121-t1994 clone, harboring mupA , fusB and exfoliatin genes, was increasingly detected among pediatric SSTIs in this hospital-based study, especially in impetigo cases, what deserves careful monitoring for its control.