Abstract
RATIONALE: Hospitalization is associated with microbiome perturbation (dysbiosis), and this perturbation is more severe in patients treated with antimicrobials. OBJECTIVES: To evaluate whether hospitalizations known to be associated with periods of microbiome perturbation are associated with increased risk of severe sepsis after hospital discharge. METHODS: We studied participants in the U.S. Health and Retirement Study with linked Medicare claims (1998-2010). We measured whether three hospitalization types associated with increasing severity of probable dysbiosis (non-infection-related hospitalization, infection-related hospitalization, and hospitalization with Clostridium difficile infection [CDI]) were associated with increasing risk for severe sepsis in the 90 days after hospital discharge. We used two study designs: the first was a longitudinal design with between-person comparisons and the second was a self-controlled case series design using within-person comparison. MEASUREMENTS AND MAIN RESULTS: We identified 43,095 hospitalizations among 10,996 Health and Retirement Study-Medicare participants. In the 90 days following non-infection-related hospitalization, infection-related hospitalization, and hospitalization with CDI, adjusted probabilities of subsequent admission for severe sepsis were 4.1% (95% confidence interval [CI], 3.8-4.4%), 7.1% (95% CI, 6.6-7.6%), and 10.7% (95% CI, 7.7-13.8%), respectively. The incidence rate ratio (IRR) of severe sepsis was 3.3-fold greater during the 90 days after hospitalizations than during other observation periods. The IRR was 30% greater after an infection-related hospitalization versus a non-infection-related hospitalization. The IRR was 70% greater after a hospitalization with CDI than an infection-related hospitalization without CDI. CONCLUSIONS: There is a strong dose-response relationship between events known to result in dysbiosis and subsequent severe sepsis hospitalization that is not present for rehospitalization for nonsepsis diagnoses.