Trends and characteristics of multidrug-resistant MRSA in Norway 2008-2020

Infections caused by multidrug-resistant (MDR) bacteria are recognized as a critical One Health concern which poses a significant threat to public health, leading to increased morbidity and mortality across both high- and low-income countries. In this study, we investigated the epidemiology and molecular mechanisms of multidrug-resistant methicillin-resistant <i>Staphylococcus aureus</i> (MDR-MRSA) strains identified in Norway from 2008 to 2020, in order to gain a better understanding of the evolution and dissemination of multidrug resistance in <i>S. aureus</i>. A total of 452 MDR-MRSA strains isolated from 429 individuals were analyzed from a dataset of 23,412 MRSA strains. Methods included epidemiological characterization, antimicrobial susceptibility testing (AST), and genetic analysis of a selection of strains using nanopore sequencing to identify antimicrobial resistance (AMR) genes and mutations, as well as their location on plasmids, SCC<i>mec</i> and other mobile genetic elements (MGEs). The study revealed an overall increasing trend in MDR-MRSA strains, with healthcare-associated strains being more prevalent among MDR-MRSA compared to the overall MRSA population. Significant heterogeneity in <i>spa</i>-types and clonal complexes exhibiting multidrug resistance was observed, with high resistance rates against multiple antibiotic groups, particularly erythromycin, ciprofloxacin/norfloxacin, tetracycline, gentamicin, and clindamycin in addition to cefoxitin. The predominant MDR-MRSA clones included t1476/CC8, t127/CC1, t189/CC188, and t030, t037/CC239. Among these, MRSA t1476/CC8 showed an upward trend toward the conclusion of the study period, indicating the emergence of a MDR-MRSA clone. A broad range of AMR genes and mutations were detected, linked to a wide variety of MGEs, highlighting the complex mechanisms of resistance development and dissemination within the MRSA population. This study highlights the rising challenge posed by MDR-MRSA strains, and reveals the multifactorial nature of AMR in <i>S. aureus</i>, thus emphasizing the importance of continued surveillance, antibiotic stewardship and infection control measures, as well as global cooperation, in order to combat the spread of these multidrug-resistant pathogens.