Staphylococcus aureus Bacteremia in Patients not Meeting Sepsis Criteria: Clinical Features, Host Immune Response and Outcomes

BACKGROUND: Limitations regarding the sensitivity and specificity of the systemic inflammatory response (SIRS) criteria prompted the recent revision in consensus definitions of sepsis and septic shock. We evaluated patients with Staphylococcus aureus bacteremia (SAB) who did not meet SIRS criteria for sepsis (SIRS-negative, SIRS-N) to compare host immune response and outcomes with SIRS-positive (P) patients. METHODS: A prospective observational study of patients hospitalized for SAB during 2012–2015 was conducted. Pro- (TNFα, IL6, IL8) and anti-inflammatory (IL10) cytokine levels (pg/mL) were compared between SIRS-N and SIRS-P patients. Outcome endpoints were day 4 persistence and 30-day mortality. RESULTS: Of the 353 study patients, 23% were SIRS-N. A similar proportion of SIRS-N and SIRS-P patients had an infection-related admitting diagnosis (70% vs. 66%, p=0.5946), and both groups received timely antibiotic administration. Less than 1/3 of SIRS-N group had abnormal WBC count, tachycardia, or tachypnea while <15% had fever/hypothermia or hypotension. Initial proand anti-inflammatory cytokine levels were significantly lower and in balance as indicated by IL10/TNF ratio in SIRS-N compared to SIRS-P patients. IL10/TNF ratio increased progressively in patients with increasing sepsis severity and mortality. CONCLUSIONS: Clinical management of patients with SAB seemed driven largely by clinician assessment rather than SIRS criteria alone, with one in 4 patients not meeting SIRS criteria. Importantly, the severity of presentation and outcomes of SAB correspond well to the magnitude of underlying imbalance in pro- and anti-inflammatory cytokine levels, supporting the updated sepsis definition as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. KEY POINTS: In a prospective observational study of 353 patients with Staphylococcus aureus bacteremia, 23% did not meet SIRS criteria for sepsis. Severity of sepsis and risk of death is supported by a dysregulated host cytokine response with progressively increasing IL10/TNF ratio.