gms | German Medical Science

Within the context of sepsis/septic shock, a „one-size-fits-all” therapeutic approach has proven to be far from perfect. Therefore, the concept of personalized medicine has recently become en vogue, necessitating the development of new biomarkers for individual therapy guidance. In this respect, point-of-care based assessment of monocytic HLA-DR expression has shown to be suitable for stratification of patients according to their risk for a complicated course/infection, enabling healthcare professionals to close the theragnostic circle of immunomodulatory therapies (e.g., G-CSF or GM-CSF). However, the results of a recently completed confirmatory French RCT for GM-CSF treatment of sepsis patients with low mHLA-DR are still pending. High plasma levels of the vasoactive peptide adrenomedullin (ADM) were also associated with poor prognosis in sepsis. Recent evidence, therefore, suggests that ADM is able to identify disease severity and treatment response more accurately than well-established biomarkers and scores. Based on experimental evidence from preclinical models and two clinical Phase I studies, an ongoing phase-II-study (AdrenoOSS-2) now investigates the efficacy and safety of Adrecizumab in patients with early septic shock and increased ADM concentrations in terms of another theragnostic approach. A more sophisticated evaluation of transcriptomic host data from next generation sequencing (NGS)- or microarray-based analyses (including deep-learning neural networks) has also shown to be of value for stratification of patients’ host response (e.g., inflammopathic, coagulopathic, adaptive) potentially enabling a precision medicine approach in sepsis. Apart from assessing the host response to infection, an NGS-based diagnostic approach has also proven suitable for early identification of the causative pathogen using free circulating nucleic acids (cell-free DNA) in plasma samples of septic patients. Taken together, an NGS-based diagnostic procedure in sepsis might represent a holistic approach for assessing both, the causative pathogen as well as the resulting host response in septic patients, enabling clinicians for early targeting the antiinfective treatment regime as well as matching immunomodulatory therapies with septic patients most likely to benefit.