Abstract
BackgroundIn the context of infection, progressive illness resulting in acute organ dysfunction is thought to be secondary to inflammatory response. Our aims were to determine risk factors for progressive illness following infection in a low-risk hospitalised cohort, including the impact of prior stain therapy.MethodsWe performed a prospective observational cohort study on two adult acute medical wards of a single tertiary academic hospital. We screened drug prescription charts of all adult acute medical admissions for inclusion criteria of inpatient administration of antibiotics for more than 24 hours for a microbiologically confirmed or clinically suspected infection. Patients were followed until admission to a high dependency unit (HDU) or intensive care unit (ICU), discharge from hospital, or to a maximum of 10 days. Outcomes were evolution of systemic inflammatory response syndrome (SIRS) criteria, white cell count and C-reactive protein measurements, and adverse clinical outcomes. We constructed multivariable models accounting for repeated within-patient measurements to determine associations between a priori selected predictors (days since admission, age, gender, Charlson score, prior statin exposure) and selected outcomes.ResultsWe enrolled 209 patients; 27.8% were statin users and the commonest infection was pneumonia (51.0%). Most (88.0%) had at least 1 SIRS criterion on admission, and 76 (37.3%) manifested additional SIRS criteria over time. Risks of admission to HDU/ICU (3.3%) and of 30-day mortality (5.7%) were low. The proportion of patients with at least 1 SIRS criterion, mean CRP, and mean WBC all decreased over time. Multivariable regression models identified days since hospital admission as the only variable associated with daily presence of SIRS criteria, WCC, or CRP (adjusted OR <1 and p < 0.0001 in all analyses). Statin exposure was not a significant predictor.ConclusionsThis cohort of ward patients treated for infection had a low risk of clinical deterioration, inflammatory markers improved over time, and statin exposure was not associated with any outcome. Future larger studies may identify risk factors for progression of illness in this population and plausible surrogate endpoints for evaluation in clinical trials.
Highlights
In the context of infection, progressive illness resulting in acute organ dysfunction is thought to be secondary to inflammatory response
Patients admitted acutely to hospital with infections are at risk of developing a progressive host inflammatory response leading to organ dysfunction [2,3,4], a group of heterogeneous syndromes defined as severe sepsis [1]
Patients managed in an intensive care unit (ICU) with sepsis are at risk developing a progressive illness trajectory associated with adverse outcomes [3,5,6]
Summary
In the context of infection, progressive illness resulting in acute organ dysfunction is thought to be secondary to inflammatory response. The ICU-treated population incidence of sepsis is substantial (1 ± 0.5 cases per 1000) [7] Given this risk of organ dysfunction [8,9], the reported minimal treatment effects and potential for harm with interventions for established organ failure [10,11], an alternative approach is to evaluate drugs with pleotropic effects to prevent progressive organ dysfunction in a pre-ICU population of patients with infection. We conducted a prospective cohort study of patients hospitalised with infection to determine the evolution of clinical and laboratory criteria for the systemic inflammatory response syndrome (SIRS) variables, and secondarily, the impact of prior statin therapy on this outcome
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