Towards Understanding the Effective Use of Antibiotics for Sepsis

Abstract

BackgroundThe 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 Prehospital Antibiotics Against Sepsis (PHANTASi) trial, did not find significant mortality benefits from early antibiotics. That subgroups of patients benefit from this practice is still plausible, given the heterogeneous nature of sepsis.Research QuestionDo 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?Study Design and MethodsWe 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.ResultsWe found a significant interaction between age and benefits of early antibiotics (P = .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 = .03).InterpretationAn 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.