257 General discussion 11 patient and disease characteristics were included. Although almost entirely based on observational studies with a different primarily aim than assessing sex-differences, and with a risk of publication bias (inherent to meta-analyses), the sex-difference in mortality found in this study calls for further investigation. Underlying causes of the higher mortality in females with S. aureus bacteremia were not addressed in our study, but it is tempting to speculate on the variety of potentially contributing factors. A biological survival disadvantage in females with S. aureus bacteremia is not immediately apparent, as males have generally worse outcomes in sepsis. However, female mice were more susceptible to lethal toxic shock caused by S. aureus enterotoxin B than male mice [22]. On a social level, a delay in health-seeking has been described in women with myocardial infarction [23], and could be present in S. aureus bacteremia as well. Differences in response to treatment may play a role, since both pharmacokinetics and pharmacodynamics are generally subject to sex influences [24]. Most disturbing would be a gender bias in healthcare delivery, which has been reported for example in women with septic shock, who experienced delays in antibiotic treatment relative to men [25]. Taking the results from chapter 9 in consideration, a gender bias in healthcare delivery is not yet excluded as a potential explanation for the sex difference in mortality in patients with S. aureus bacteremia. Concluding remarks Decolonization of MRSA carriership can be optimized on the levels of identification of carriers, treatment initiation, and treatment efficacy. Treatment goal and likelihood of successful prolonged eradication – driven by individual risk factors for treatment failure and risk of recolonization in the environment – should guide the eligibility for MRSA decolonization treatment in the individual patient. Future research would gain clinical applicability from reporting the carrier status of household contacts, long-term follow-up cultures, and reporting genotyping in case of failure. In order to maintain a low MRSA prevalence, the potential leakages of the MRSA cascade of care should be addressed. The details of this cascade may vary between countries, but the impact of MRSA extends beyond borders. Large practice variations for S. aureus bacteremia exist throughout the world, emphasizing the complex challenge of managing this heterogeneous disease. Complications such as acute kidney injury and persistent bacteremia frequently occur in patients with S. aureus bacteremia, and their management is for a large part based on clinical experience rather than robust data. Female sex is a risk factor for mortality in S. aureus bacteremia, and the underlying cause should be unraveled. In a disease as common and frequently lethal as Staphylococcus aureus bacteremia, it is essential to internationally standardize clinical definitions and identify treatment strategies in order to improve patient outcomes.
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