Towards understanding the effective use of antibiotics for sepsis.

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The benefits of early antibiotics for sepsis have recently been questioned. Evidence for this mainly comes from observational studies. The only randomized trial on this subject, the PHANTASi trial, did not find significant mortality benefits from early antibiotics. It is still plausible that subgroups of patients benefit from this practice, given the heterogeneous nature of sepsis.Do subgroups of sepsis patients experience 28-day mortality benefits from early administration of antibiotics in a prehospital setting? And what key traits drive these benefits?and Methods: We used machine learning to conduct exploratory partitioning cluster analysis to identify possible subgroups of sepsis patients who may benefit from early antibiotics. We further tested the influence of several traits within these subgroups using a logistic regression model.We found a significant interaction between age and benefits of early antibiotics (p=0.03). When we adjusted for this interaction and several other confounders, there was a significant benefit of early antibiotic treatment (OR = 0.07; 95%-CI = 0.01-0.79; p = 0.03).An interaction between age and benefits of early antibiotics for sepsis has not been reported before. When validated, it can have major implications for clinical practice. This new insight into benefits of early antibiotic treatment for younger sepsis patients may enable more effective care.


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Authors: M Schinkel, K Paranjape, J Kundert, R S Nannan Panday, N Alam, P W B Nanayakkara

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