Early Detection of Plasma D-Lactate: Toward a New Highly-Specific Biomarker of Bacteraemia?

Background: Bloodstream infections are a leading cause of mortality. Their detection relies on blood cultures (BCs) but time to positivity is often between tens of hours and days. D-lactate is a metabolite widely produced by bacteria but very few in human. We aimed to evaluate D-lactate, Dlactate/L-lactate ratio and D-lactate/total lactate ratio in plasma as potential early biomarkers of bacteraemia on a strictly biological standpoint.Methods: A total of 228 plasma specimens were collected from patients who had confirmed bacteraemia (n = 131) and healthy outpatients (n = 97). Specific L-lactate and D-lactate analyses were performed using enzymatic assays and analytical performances of D-lactate, D-lactate/total lactate and D-lactate/L-lactate ratios for the diagnosis of bacteraemia were assessed.Results: A preliminary in vitro study confirmed that all strains of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were able to produce D-lactate at significant levels. In patients, plasma D-lactate level was the most specific biomarker predicting a bacteraemia profile with a specificity and predictive positive value of 100% using a cut-off of 131 & mu;mol.L- 1. However, sensitivity and negative predictive value were rather low, estimated at 31% and 52%, respectively. D-lactate displayed an Area Under Receiver Operating Characteristic (AUROC) curve of 0.696 with a P value < 0.0001. There was no difference of D-lactate levels between BCs bottles positive for Gram-positive or Gram-negative bacteria (p = 0.55).Conclusion: D-lactate shows promise as a specific early biomarker of bacterial metabolism. The development of rapid automated assays could raise clinical applications for infectious diseases diagnosis including early bacteraemia prediction.