Hospitalization Type and Subsequent Severe Sepsis

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)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(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-infectionrelated 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 infectionrelated 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.

Late mortality after sepsis: propensity matched cohort study

“…With the relatively small number of terminal admissions, we were not able to detect a difference in the proportion for infection between the matched comparison cohorts. Nonetheless, the high number of terminal admissions for infection suggests that heightened risk of infection, perhaps as a result of a sustained immunosuppression or microbiome perturbation,42 could be a potential target for reducing late mortality from sepsis.…”

Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study

“…Still, demonstrating such a subtle effect in a heterogeneous patient population may be quite hard. Small descriptive studies of faecal microbiota in critically ill patients have associated higher bacterial diversity with better outcome37 38 and a large retrospective cohort study-associated dysbiosis in the gut with higher incidence of subsequent severe sepsis 39. The latter identified 43 095 hospitalisations among 10 996 patients and divided them into three diagnosis groups based on likelihood of intestinal microbiota disturbance (non-infection: not likely, infection: likely, C. difficile infection: very likely).…”

The immunopathology of sepsis and potential therapeutic targets

“…Conversely, dysbiosis in the gut has been linked to the subsequent hospitalization of patients with sepsis, which suggests an association between the composition of the gut microbiota and sepsis susceptibility 74 . The composition of the gut microbiome of healthy individuals influences cytokine release by blood leukocytes in a stimulus-specific and cytokinespecific way 75 .…”