Temperature Trajectory Subphenotypes in Oncology Patients with Neutropenia and Suspected Infection
Nicole Benzoni, Kyle A. Carey, Alice F. Bewley, Jeff Klaus, Brian M. Fuller, Dana P. Edelson, Matthew M. Churpek, Sivasubramanium V. Bhavani, Patrick G. Lyons
Abstract
Abstract Rationale Despite etiologic and severity heterogeneity in neutropenic sepsis, management is often uniform. Understanding host response clinical subphenotypes might inform treatment strategies for neutropenic sepsis. Objectives In this retrospective two-hospital study, we analyzed whether temperature trajectory modeling could identify distinct, clinically relevant subphenotypes among oncology patients with neutropenia and suspected infection. Methods Among adult oncologic admissions with neutropenia and blood cultures within 24 hours, a previously validated model classified patients’ initial 72-hour temperature trajectories into one of four subphenotypes. We analyzed subphenotypes’ independent relationships with hospital mortality and bloodstream infection using multivariable models. Measurements and Main Results Patients (primary cohort n = 1,145, validation cohort n = 6,564) fit into one of four temperature subphenotypes. “Hyperthermic slow resolvers” (pooled n = 1,140 [14.8%], mortality n = 104 [9.1%]) and “hypothermic” encounters (n = 1,612 [20.9%], mortality n = 138 [8.6%]) had higher mortality than “hyperthermic fast resolvers” (n = 1,314 [17.0%], mortality n = 47 [3.6%]) and “normothermic” (n = 3,643 [47.3%], mortality n = 196 [5.4%]) encounters (P < 0.001). Bloodstream infections were more common among hyperthermic slow resolvers (n = 248 [21.8%]) and hyperthermic fast resolvers (n = 240 [18.3%]) than among hypothermic (n = 188 [11.7%]) or normothermic (n = 418 [11.5%]) encounters (P < 0.001). Adjusted for confounders, hyperthermic slow resolvers had increased adjusted odds for mortality (primary cohort odds ratio, 1.91 [P = 0.03]; validation cohort odds ratio, 2.19 [P < 0.001]) and bloodstream infection (primary odds ratio, 1.54 [P = 0.04]; validation cohort odds ratio, 2.15 [P < 0.001]). Conclusions Temperature trajectory subphenotypes were independently associated with important outcomes among hospitalized patients with neutropenia in two independent cohorts.