AUTHOR=Meini Simone , Sozio Emanuela , Bertolino Giacomo , Sbrana Francesco , Ripoli Andrea , Pallotto Carlo , Viaggi Bruno , Andreini Roberto , Attanasio Vittorio , Rescigno Carolina , Atripaldi Luigi , Leonardi Silvia , Bernardo Mariano , Tascini Carlo 

TITLE=D-Dimer as Biomarker for Early Prediction of Clinical Outcomes in Patients With Severe Invasive Infections Due to Streptococcus Pneumoniae and Neisseria Meningitidis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.627830

DOI=10.3389/fmed.2021.627830

ISSN=2296-858X

ABSTRACT=<p>Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection; no current clinical measure adequately reflects the concept of dysregulated response. Coagulation plays a pivotal role in the normal response to pathogens (immunothrombosis), thus the evolution toward sepsis-induced coagulopathy could be individuate through coagulation/fibrinolysis-related biomarkers. We focused on the role of D-dimer assessed within 24 h after admission in predicting clinical outcomes in a cohort of 270 patients hospitalized in a 79 months period for meningitis and/or bloodstream infections due to <italic>Streptococcus pneumoniae</italic> (<italic>n</italic> = 162) or <italic>Neisseria meningitidis</italic> (<italic>n</italic> = 108). Comparisons were performed with unpaired <italic>t</italic>-test, Mann-Whitney-test or chi-squared-test with continuity correction, as appropriate, and multivariable logistic regression analysis was performed with Bayesian model averaging. In-hospital mortality was 14.8% for the overall population, significantly higher in <italic>S. pneumoniae</italic> than in <italic>N. meningitidis</italic> patients: 19.1 vs. 8.3%, respectively (<italic>p</italic> = 0.014). At univariable logistic regression analysis the following variables were significantly associated with in-hospital mortality: pneumococcal etiology, female sex, age, ICU admission, SOFA score, septic shock, MODS, and D-dimer levels. At multivariable analysis D-dimer showed an effect only in <italic>N. meningitidis</italic> subgroup: as 500 ng/mL of D-dimer increased, the probability of unfavorable outcome increased on average by 4%. Median D-dimer was significantly higher in <italic>N. meningitidis</italic> than in <italic>S. pneumoniae</italic> patients (1,314 vs. 1,055 ng/mL, <italic>p</italic> = 0.009). For <italic>N. meningitidis</italic> in-hospital mortality was 0% for D-dimer &lt;500 ng/mL, very low (3.5%) for D-dimer &lt;7,000 ng/mL, and increased to 26.1% for D-dimer &gt;7,000 ng/mL. Kaplan-Meier analysis of in-hospital mortality showed for <italic>N. meningitidis</italic> infections a statistically significant difference for D-dimer &gt;7,000 ng/mL compared to values &lt;500 ng/mL (<italic>p</italic> = 0.021) and 500–3,000 ng/mL (<italic>p</italic> = 0.002). For <italic>S. pneumoniae</italic> the mortality risk resulted always high, over 10%, irrespective by D-dimer values. In conclusion, D-dimer is rapid to be obtained, at low cost and available everywhere, and can help stratify the risk of in-hospital mortality and complications in patients with invasive infections due to <italic>N. meningitidis</italic>: D-dimer &lt;500 ng/mL excludes any further complications, and a cut-off of 7,000 ng/mL seems able to predict a significantly increased mortality risk from much &lt;10% to over 25%.</p>