Annette Westgeest

83 Genetic determinants in MRSA carriage 5 characteristics, antibiotic regimen, and isolate characteristics are all considered to contribute to decolonization treatment outcomes [7–9]. Different MRSA clones have emerged throughout the world with a high variety in virulence factors [10]. The rapid developments in the field of genetic diagnostics, especially whole-genome sequencing (WGS), have expanded the knowledge of the complexity and heterogeneity of this pathogen. MRSA strains produce a broad range of virulence factors, such as toxins, immune evasion factors, and adhesion proteins [11]. These virulence determinants are mostly carried on mobile genetic elements (MGEs), such as pathogenicity islands, plasmids, or bacteriophages [3]. Furthermore, virulence determinants can vary between hospital-associated, community-associated, and livestock-associated (LA) MRSA strains [12]. WGS of MRSA strains has been deployed extensively for infection control purposes. It has proven to be of great value in the epidemiology and outbreak management of MRSA [13]. In addition, WGS allows for molecular characterization of isolates by identifying clinically relevant genetic determinants that can help to predict response to decolonization treatment. So far, microbial genomics is not yet broadly applied to identify determinants related to MRSA eradication treatment outcome [14]. As an example, the presence of Panton-Valentine leucocidin (PVL) genes and genes associated with mupirocin resistance were associated with successful eradication outcome [9, 15]. A recent study elaborated on genetic factors and carriage duration, and showed a potential role of bacteriophage-related chemotaxis inhibitory protein encoded by chp [8]. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. Ultimately, differentiating between MRSA carriers that will benefit from an eradication treatment and carriers more prone to eradication failure may enable personalized medicine. In this explorative pilot cohort study, we evaluated genomic characteristics that are associated with MRSA decolonization failure. This was established by linking WGS data of MRSA isolates to clinical patient characteristics. Methods This cohort study was conducted at the University Medical Center Groningen, a tertiary hospital in the Northern part of the Netherlands, between 2017 and 2022. The prevalence of MRSA carriage in the Netherlands during this time was < 1%. During these years, genetic analyses of first MRSA isolates (both from carriage and infection) had been performed in all index patients and most of the healthcare workers, for the purpose of surveillance and outbreak management. Genetic analysis was not performed in healthcare workers who were positive at their pre-employment

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