Early Platelet Dynamics During <i>Staphylococcus Aureus</i> Bacteremia is Associated with Dysregulated Cytokine Response and Predictive of Microbial Persistence and Mortality

Abstract

Background: Platelets play key roles in host immune response during sepsis. Microbial persistence and early dysregulated cytokine response predict poor outcomes in patients with Staphylococcus aureus bacteremia (SAB). Our objective was to determine the relationship between early platelet trends and cytokine response, microbial persistence and 30-day mortality in patients with SAB. Methods: A two-center observational study was conducted in hospitalized patients with monomicrobial SAB. Electronic medical records were reviewed for pertinent demographic, laboratory, and clinical information. Eligible subjects were grouped by platelet count at onset and Day 4 of SAB: normal platelet (NP, > 150 x 109/L) and thrombocytopenia (TC, < 150 x 109/L). The groups were compared for clinical characteristics and outcomes. Findings: 812 patients met inclusion criteria. The median age was 59 years with MRSA accounting for 34% of SAB. The most common comorbidities were hypertension followed by diabetes then renal disease. Thrombocytopenia (TC) occurred in 29% of patients at SAB onset: 15% (n = 120) were mild and 14% (n = 114) were moderate-tosevere (MS). Compared to patients with normal platelet (NP) at SAB onset (n = 578), higher proportion of patients with TC had alcohol use disorder (p = 0·015), active malignancy (p = 0·002), liver disease (p < 0·001), in addition to requiring intensive care unit (ICU) level of care during hospital stay (p < 0·001). TC patients had a longer duration of bacteremia (3 days vs 2 days; p = 0·008) and higher risk for 30-day mortality (18% vs 6%; p < 0·001) overall compared to those with NP. Changes in platelet count from SAB onset to Day 4 differed significantly between those with persistent (PB) versus resolving bacteremia (RB). Notably, patients who had NP at SAB onset but developed new onset of TC by Day 4 had a higher risk for 30-day mortality compared to those who maintained NP at Day 4 (20% vs 4%; p < 0·001). Those with recovery of their platelet count from TC to NP by Day 4 (n = 20) had their SAB shortened by one day (2 days vs 3 days; p = 0·413) and trended toward lower risk for 30-day mortality (5% vs 22%; p = 0·068) compared to those with sustained TC by Day 4 (n = 88). Interpretation: Our results suggest that platelet dynamics during early course of SAB are associated with dysregulated cytokine response and predictive of 30-day mortality. Future studies should be conducted to assess the impact of utilizing platelet count within the first four days of S. aureus bacteremia to guide clinical interventions and to further investigate S. aureus virulence factors that impair recovery of platelet count in patients with thrombocytopenia. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by the institutional review boards at each of the study site.