Hospitalization Type and Subsequent Severe Sepsis

Am J Respir Crit Care Med. 2015 Sep 1;192(5):581-8. doi: 10.1164/rccm.201503-0483OC.


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.

Keywords: dysbiosis; humans; microbiota; patient readmission; self-controlled case series.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Clostridioides difficile
  • Dysbiosis / epidemiology*
  • Enterocolitis, Pseudomembranous / epidemiology*
  • Female
  • Hospitalization / statistics & numerical data*
  • Humans
  • Incidence
  • Information Storage and Retrieval
  • Longitudinal Studies
  • Male
  • Medicare
  • Patient Readmission / statistics & numerical data
  • Retrospective Studies
  • Risk Factors
  • Sepsis / epidemiology*
  • United States / epidemiology


  • Anti-Bacterial Agents