82 Chapter 5 Abstract Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. The aim of this study was to explore genetic characteristics that are associated with MRSA decolonization failure. This cohort study was performed in a tertiary care hospital in the Netherlands. Patients with≥1 positive MRSA culture from any site and with available whole -genome sequencing data of the MRSA isolate between 2017 and 2022 were included. Lineages, resistance, and virulence factors were stratified by MRSA decolonization outcome. In total, 56 patients were included: 12/56 (21%) with treatment failure and 44/56 (79%) with successful decolonization (with or without preceding treatment). A significant association was found between ciprofloxacinresistant lineages and failure of eradication (OR 4.20, 95%CI 1.11–15.96, P = 0.04). Furthermore, livestock-associated MRSA and the major community-associated MRSA lineages ST6-t304 and ST8-t008 were associated with successful eradication treatment or spontaneous clearance. In conclusion, this explorative study showed a higher eradication failure rate in complicated MRSA carriers with ciprofloxacinresistant MRSA lineages, which are predominantly healthcare-associated. Further studies are warranted to confirm the higher eradication failure risk of ciprofloxacinresistant lineages, and identify the underlying mechanisms. Introduction Methicillin-resistant Staphylococcus aureus (MRSA) is a global health threat with high morbidity and mortality rates [1]. Colonization with MRSA leads to increased infection rates of up to 25% [2, 3]. The Netherlands has one of the lowest levels of endemic MRSA in the world [4]. This low prevalence is for a large part attributed to a successful ‘search and destroy’ policy aiming at MRSA carriage, that has been executed for over three decades [5]. This policy consists of screening and preemptive strict isolation of patients with increased risk of MRSA carriage when hospitalized and subsequent decolonization treatment when carriage is found. Response to decolonization treatment is highly variable; in some patients, eradication treatment fails despite multiple attempts, in others colonization is self-limiting without treatment [6, 7]. Spontaneous clearance or persistent carriership is driven by a complex host–pathogen interaction, which is largely unraveled. Furthermore, antimicrobial treatment (i.e., eradication therapy) adds to this complex interaction, and introduces pharmacodynamic and pharmacokinetic effects. In summary, patient
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