High Early Mortality in Patients With Staphylococcus aureus Bloodstream Infection: A Call for Action
Authors: Mylotte Joseph M. 
Published: February 2025

Objectives More than half of all deaths within one month of identification of Staphylococcus aureus bloodstream infection (SABI) occur within seven days of the first positive culture. However, there has not been a specific evaluation of studies of early mortality in patients with SABI. The objectives were to analyze studies that reported the seven-day all-cause mortality rate in patients with SABI and risk factors for this outcome. We also hypothesized that studies of gram-negative bloodstream infection (GNBI) or all episodes of BI (gram-negative and gram-positive, including fungemia) that reported seven-day all-cause mortality might provide other methods for predicting this outcome. Methods Early mortality was defined as death within seven days following the first day blood cultures were positive. Of 751 studies of SABI reviewed, 23 reported seven-day all-cause mortality rates. Studies were categorized into three groups: those reporting data on all SABI, methicillin-susceptible SABI, or methicillin-resistant SABI alone. Four studies of SABI evaluated risk factors for early mortality. Of 545 studies of GNBI or all episodes of BI, six evaluated factors predictive of seven-day all-cause mortality. Results There was a significant difference in the mean seven-day all-cause mortality rate between the three groups with SABI. However, there was no significant difference between the three groups when the metric was the proportion of all deaths within the first 30 days following the first positive blood culture that occurred within the first seven days (early death proportion). Overall, the median early death proportion for 23 studies was 53% (interquartile range 49–57). Four studies reported risk factors for early mortality, but all had methodological limitations. Analysis of six studies of GNBI or all BI revealed that an acute severity of illness model (bloodstream infection mortality risk score) by itself accurately predicted seven-day all-cause mortality. Conclusions Concordance in the early death proportion in 23 studies suggests a distinct group of patients with SABI is at risk for early mortality. However, methodologically sound studies are needed to identify all factors (clinical, diagnostic, and pathogen) associated with early mortality to evaluate methods to potentially reduce mortality in this group. Acute severity of illness models should be evaluated for predicting early mortality in patients with SABI. Plain Language Summary Bloodstream infections in which bacteria like Staphylococcus aureus enter the bloodstream are deadly serious for patients. In fact, studies of S. aureus bloodstream infection (SABI) mortality show that among all deaths within 30 days of the first positive blood culture test, 50% of the deaths occurred within the first seven days after the positive test. However, randomized controlled treatment trials of SABI have typically excluded the patients in the “early mortality” group, resulting in an overall lower mortality rate in trials that may inflate the effectiveness of the treatment and affect how clinicians manage patients with SABI. This article analyzes studies reporting SABI early mortality and specifically focuses on studies that identified risk factors for early mortality. The findings support standardization of the definition of early mortality as “all-cause mortality within seven days of the first positive blood culture.” However, studies that evaluated risk factors for early mortality were not well designed. Future studies need to focus on improving the design for identifying risk factors for early mortality of SABI to develop interventions to potentially reduce the 30-day mortality of this infection.