266 Chapter 11 different endotypes (designated Mars 1-4) [44]. The biomarkers BPGM and TAP2 reliably identified patients with Mars1 endotype, which was associated with increased mortality at day 28 [44]. Endotypes are dynamic and a significant proportion of subjects transition endotypes during the acute phase of septic shock. Changes in endotype assignment have implications on response to corticosteroids and outcomes [45]. These sepsis signatures or endotypes could significantly add to traditional biomarkers, and aid a personalized approach for subject selection in clinical trials and in sepsis management. Personalized antibiotic treatment in sepsis Adequate antibiotic treatment, defined as using an agent(s) to which the pathogen is ultimately shown to be susceptible, improves survival in patients with sepsis and is therefore a key prognostic factor [46]. In sepsis management, there is great focus on timely administration of appropriate antimicrobial treatment. A triage model with special attention to severe sepsis assessing 1837 patients in the Emergency Department in Sweden led to an improvement in time to antibiotic treatment and reduction in length of hospital stay [47]. Aside from triage and early drug administration policies, it is crucial to take into account individualized patient-related factors when selecting initial antibiotic treatment. While antibiotic treatment guidelines consider infection source and the presentation setting, community-acquired or healthcare-associated sepsis, physicians should carefully evaluate further patient-related factors. Initial broad-spectrum antimicrobial treatment is recommended in patients with healthcare-associated sepsis, which could be related to multidrug-resistant (MDR) bacteria (Box 2)[48]. Box 2 - Key risk factors for infection due to MDRa bacteria [48] Antimicrobial therapy in preceding 90 days. Current hospitalization of >4 days. High frequency of antimicrobial resistance in the community or in the specific hospital unit. Presence of risk factors for healthcare-associated infection: • hospitalization for >48h in the preceding 90 days • residence in nursing home or extended care facility • at home infusion therapy • chronic dialysis within 30 days • home wound care • family member with MDR pathogen Immunosuppressive disease. Immunosuppressive therapy. a MDR, multidrug-resistant
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