270 Chapter 11 Table 3. Limitations to develop precision medicine in sepsis and septic shock It is necessary to find a way to stratify patients in relevant discrete groups. The contribution of comorbidities in precision medicine should be determined. Comorbidities could be part of the variables identifying discrete groups or it may be unrelated. Also, comorbidities may be causal with regards to the phenotypic variation. With the rapid technological advances such as next-generation sequencing, enormous amounts of data are generated. New skills to analyse these data need to be developed and integrated in the clinic. In contrast to cancer, sepsis is a rapidly evolving process that changes on a minute to minute basis and so needs rapid action. The rapid changes in these complex inflammatory responses provide a huge challenge for personalized medicine in sepsis. Another challenge lies in the potential increased complexity for healthcare providers, when confronted with the introduction of novel diagnostic or therapeutic measures while their time is often already limited. The rapid interpretation of various (novel) diagnostic tests in the dynamic clinical context of sepsis requires training, especially if these yield contradictory/misleading data, which may occur due to limited sensitivity and specificity. Sepsis often presents in patients with multiple comorbidities who may be treated primarily by physicians in varied medical specialties. It is essential and our responsibility to educate all healthcare providers that may encounter septic patients about this complex syndrome. Table 4. Road Map of Recommendations and Perspectives for sepsis Recommendations RDTs have become useful tools for the diagnosis of sepsis complementing BCs. Their performance and accuracy (especially for AST), as well as their clinical and economic benefits, need to be further investigated. RDTs will likely be valuable, future tools for the diagnosis of sepsis. The combination of RDTs and BCs seems to be a worthwhile strategy to enhance the microbiological diagnosis in patients with sepsis and to shorten the time to initiation of appropriate antimicrobial therapy. When assessing (new) RDTs, it is important to focus on outcomes, including time to appropriate antimicrobial therapy. Determining the identity of the pathogen is of some importance for rapid molecular diagnosis, but the rapid determination of its antibiotic susceptibility is the key, and so this needs to have the highest priority. To have a significant clinical impact, RDT results should be delivered with a real-time decision support, such as an automated information system and, ideally, infectious disease/ microbiology specialist consultation and an antimicrobial stewardship program. Regarding the host defense, the notion that the course of sepsis is now more protracted due to fast recognition and improved supportive care, is important for understanding the pathophysiological mechanisms that impact on patient outcomes. When searching for novel biomarkers for sepsis, it is essential to assess their clinical utility. They should be measurable in easy obtainable samples, ideally via a rapid bedside test with limited hands-on time, and lead to rapid decision-making for the attending physician confronted with the septic patient. Investigators need to identify biomarkers that are more or less likely to respond to a specific intervention (predictive markers).
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