252 Chapter 11 success rate in patients treated with oral rifampin and doxycycline. Due to the retrospective design of the study and the small sample size, the causal relationship of this antimicrobial regimen with the higher success rate is not yet indisputably proven. To evaluate this further, we are currently conducting the CLEANEST study, a multicenter cluster-randomized trial comparing rifampin-doxycycline with rifampintrimethoprim for the treatment of complicated MRSA colonization. Apart from recolonization risks and individual risk factors for treatment failure, differences in genetic characteristics of the MRSA isolates may play a role in the probability of successful eradication. In chapter 5, we performed an explorative study on genetic determinants of MRSA isolates and their association with decolonization treatment outcome. We found a higher eradication failure rate in complicated MRSA carriers with ciprofloxacin-resistant MRSA lineages, which are mostly healthcareassociated. Although limited by a small and heterogenous patient population, this study suggests an effect of pathogen-associated factors on the success rates of MRSA eradication treatments as well. These pathogen-associated factors potentially interact with host factors, and this complex host-pathogen interaction adds to the likelihood of successfully eradicating individual MRSA carriers, in addition to the effectivity of the antimicrobial eradication treatment. A more individualized treatment approach could potentially be achieved with a deeper understanding of the genetic determinations and host-pathogen interaction. In conclusion, there is room for improvement in every step of the cascade of MRSA care, in order to optimize the continuity of the cascade (Figure 1). These different targets at different levels underscore the importance of taking a comprehensive view when addressing potential healthcare improvements, and applying it to the local situation.
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