D-dimer predicts clinical outcomes in N. meningitidis infections

Increasing D-dimer is a useful predictor of negative clinical outcomes among individuals with invasive infections driven by Neisseria Meningitidis, suggests a study.

“For invasive infections caused by N. meningitidis, D-dimer is confirmed to be a rapidly obtainable, low cost, and widely available biomarker, capable of predicting unfavourable clinical outcomes,” the researchers said.

This retrospective study, conducted over 79 months, recruited 90 patients with meningitis or bloodstream infection caused by N. meningitidis (n=47) or Streptococcus pneumoniae (n=43), with a median age of 19 and 58 years, respectively. The researchers assessed biomarkers within 24 h.

Univariate analysis revealed that increasing D-dimer significantly correlated with in-hospital mortality among patients with N. meningitidis infections (odds ratio [OR], 1.360, 95 percent confidence interval [CI], 1.063–1.889). [Am J Med 2025;138:504-512]

In multivariate analysis, increasing D-dimer was also significantly associated with the composite outcome of in-hospital mortality, amputations, hearing loss, or neurological sequelae (OR, 1.037, 95 percent CI, 1.001–1.074).

Protein C and activated partial thromboplastin time (aPTT) were potential biomarkers as well in N. meningitidis infections, with the former showing a trend toward lower levels in nonsurvivors (26 percent vs 48 percent) and in those with the composite outcome (32 percent vs 51 percent); the latter, on the other hand, was prolonged in nonsurvivors (51.3 vs 35.3; p=0.003), as confirmed in univariate analysis (OR, 1.122, 95 percent CI, 1.031–1.253).

Among patients with S. pneumonia infection, nonsurvivors had significantly lower antithrombin (70 percent vs 81 percent; p=0.038), as confirmed in univariate analysis (OR, 0.961, 95 percent CI, 0.921–0.997).

For the overall population, multivariate analysis showed that increasing age predicted mortality (OR, 1.043, 95 percent CI, 1.010–1.077), while S. pneumoniae aetiology was associated with the composite outcome (OR, 6.024, 95 percent CI, 1.798–20.180).

“Our study suggests a potential role for aPTT prolongation and protein C decrease as predictors of negative clinical outcomes in case of N. meningitidis infections, and for AT decrease in case of S. pneumoniae infections,” the researchers said.

Personalized approach

In 2001, the European Medicines Agency approved drotrecogin alfa, a recombinant human activated protein C, for the treatment of sepsis based on the findings of the PROWESS study. In 2012, however, it was withdrawn due to the absence of significant reduction in 29- and 90-day mortality. [N Engl J Med 2001;344:699-709; N Engl J Med 2012;366:2055-2064]

"In our opinion, a personalized approach to different models of sepsis could allow the identification of those patients who would benefit the most from administration of drugs acting on the coagulation system,” the researchers said. 

“Measurements of aPTT and protein C levels are widely available, making them potentially valuable biomarkers in case of N. meningitidis invasive infections,” they added.

However, further studies are needed to determine whether the N. meningitidis model could be used in other Gram-negative bacteria models and whether similar biomarker patterns could be proposed, according to the researchers.

"Diagnostic and therapeutic approaches to sepsis syndromes should be pathogen focused,” they said.