Clinical significance of inflammatory markers for evaluating disease severity of mixed-pathogen bloodstream infections of both Enterococcus spp. and Candida spp

Abstract

Objective: In recent decades, there has been a notable increase in the morbidity and mortality rates linked to bacteremia and candidemia. This study aimed to investigate the clinical significance of inflammatory markers in assessing the disease severity in critically ill patients suffering from mixed-bloodstream infections (BSIs) due to Enterococcus spp. and Candida spp.

Methods: In this retrospective research, patients diagnosed with BSIs who were admitted to the intensive care unit (ICU) during the period of January 2019 to December 2022 were analyzed. The patients were divided into two groups: a mixed-pathogen BSI group with both Enterococcus spp. and Candida spp., and a single-pathogen BSI group with only Enterococcus spp. The study examined the differences in inflammatory marker levels and disease severity, including Acute Physiology and Chronic Health Evaluation (APACHE) II scores, duration of ICU stay, and 30-day mortality, between the two groups. Furthermore, we sought to scrutinize the potential associations among these aforementioned parameters.

Results: The neutrophil-to-lymphocyte ratios (NLRs) and levels of plasma C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) in the mixed-pathogen BSI group were higher than those in the single-pathogen BSI group. Spearman's rank correlation analysis showed that NLRs and plasma CRP and IL-6 levels were positively correlated with disease severity in the mixed-pathogen BSI group. Further, the levels of plasma IL-8 and TNF-α were also positively correlated with ICU stay duration and 30-day mortality. In multivariate analysis, plasma CRP and IL-6 levels were independently associated with 30-day mortality.

Conclusion: Mixed-pathogen BSIs caused by Enterococcus spp. and Candida spp. may give rise to increased NLRs and plasma CRP, IL-6, IL-8, and TNF-α levels in comparison to BSI caused by Enterococcus spp. only, thus leading to elevated disease severity in critically ill patients.

Keywords: 30-Day mortality; Bloodstream infection; C-reactive protein; Disease severity; Pro-inflammatory cytokine.

Fig. 1

Flow chart showing the inclusion and exclusion criteria.

Fig. 2

Distribution of pathogens in the two groups. The numbers in parentheses represent the number of cases.

Fig. 3

Thirty-day survival curves for patients in two groups. Black and red lines represent 30-day survival curves for the single- and mixed-pathogen BSI groups, respectively. p < 0.05 indicates statistical significance.

Fig. 4

Comparison of inflammatory marker levels between the two groups. Inflammatory markers include WBC counts (a), NLRs (b), plasma PCT levels (c), plasma CRP levels (d), plasma IL-6 levels (e), plasma IL-8 levels (f), and plasma TNF-α levels (g). * and ** represent p < 0.05 and p < 0.01, respectively.

Fig. 5

Scatterplot shows the correlations between inflammatory markers and disease severity. Inflammatory markers include WBC counts (a), NLRs (b), plasma PCT levels (c), plasma CRP levels (d), plasma IL-6 levels (e), plasma IL-8 levels (f), and plasma TNF-α levels (g). Disease severity was presented as APACHE II scores, ICU stay duration and 30-day mortality. r: Spearman's correlation conefficient. For the analysis, the ICU hospitalization days of patients who died within 30 days were also considered as part of the ICU stay duration.