The Associations of Gram-Positive Cocci and Gram-Negative Rods with Disease Severity and Mortality in Critically Ill Patients: A Retrospective Cohort Study

Background: Despite advances in intensive care medicine, the mortality rate of patients with sepsis remains high. The differences in pathogenic mechanisms between gram-positive cocci (GPC) and gram-negative rod (GNR) bacteremia are well-documented, but the relationship between bacterial types and clinical outcomes remains unclear, particularly regarding the discrepancy between severity at emergency department (ED) / intensive care unit (ICU) presentation and subsequent mortality. Patients and Methods: Of the adult patients who presented to two Japanese tertiary hospitals' EDs with suspected infections in 2018–2022, we included those with positive blood cultures who were admitted to the ICU or emergency ward. The primary outcomes were 7-day and 28-day mortality. The secondary outcomes were diagnoses of sepsis and septic shock. We calculated adjusted risk differences (aRDs) and adjusted risk ratios (aRRs) between the GPC and GNR groups using modified Poisson and least-squares regression analyses, adjusting for age, sex, malignancy, immunosuppressive therapy, hemodialysis, and intravascular device use. Results: Of the 259 patients, 107 (41.3%) had GPC bacteremia and 152 (58.7%) had GNR bacteremia. Staphylococcus aureus and Escherichia coli were the most common pathogens in each group. GPC bacteremia was associated with higher mortality at both 7 days (aRD 8.9%, 95%CI: 1.3−16.4; aRR 3.48, 95%CI: 1.29−9.36) and 28 days (aRD 10.6%, 95%CI: 1.8–19.5; aRR 2.65, 95%CI: 1.21−5.83) versus GNR bacteremia. However, the GPC bacteremia patients showed less severe presentations at ED arrival, with a lower sepsis diagnosis rate (aRD −12.8%, 95%CI: −24.7 to −0.8; aRR 0.81, 95%CI: 0.66–0.99), lower qSOFA scores, and lower lactate levels (1.9 vs. 2.5 mmol/L). This pattern of higher mortality despite less-severe initial presentations was consistently observed in analyses of sepsis patients and in a comparison of S. aureuswith E. coli bacteremia. Conclusions: GPC bacteremia, despite its less severe clinical presentation at ED arrival compared to GNR bacteremia, was associated with higher mortality. Clinicians should not be misled by the apparently milder initial organ dysfunction in GPC bacteremia, as these patients require careful monitoring and appropriate treatment regardless of presentation severity. These findings highlight the importance of identifying the bacterial species in the risk stratification and management of bacteremia patients in critical-care settings.