Blood biomarker algorithms for the diagnosis of mycoplasma pneumoniae respiratory infections

Per Venge,Staffan Eriksson,Karlis Pauksen

doi:10.1016/j.jim.2020.112908

Abstract

The correct diagnosis of acute infections as to bacteria, mycoplasma or virus is a clinical challenge and has a great impact on the therapeutic decisions. Current diagnostic tests of mycoplasma pneumoniae infections of the respiratory tract such as PCR and serology are either somewhat unreliable or slow and do not entirely meet the clinical needs of accurate and fast diagnosis. The aim of this report was to examine a panel of candidate biomarkers and their capacity to distinguish mycoplasma pneumoniae respiratory infections from respiratory infections caused by either bacterial or virus. MethodPatients with confirmed etiology of their acute respiratory infections (n = 156) were included of which 28 patients were diagnosed with mycoplasma pneumoniae. Blood was taken before any antibiotics treatment and analysed for Azurocidin (HBP), Calprotectin, CRP, Human Neutrophil Lipocalin (HNL), Interferon γ-induced Protein 10 kDa (IP-10), Procalcitonin (PCT), Thymidine Kinase 1 (TK1), TNF-Related Apoptosis-Inducing Ligand (TRAIL). ResultsIndividually the concentrations of IP-10, TK1 and P-HNL distinguished mycoplasma pneumoniae from bacterial infections with AUCs of 0.79–0.85. However, in combination, TK1 with either IP-10 or P-HNL showed an AUC of 0.97–0.95. In the distinction between mycoplasma pneumoniae and viral respiratory infections CRP, Calprotectin and TRAIL showed individual AUCs of 0.94–0.84. Together with either P-HNL dimer or PCT, CRP showed AUCs of 0.97. ConclusionOur results indicate that it may be possible to design useful diagnostic algorithms of biomarkers that could help distinguish mycoplasma pneumoniae from respiratory infections caused by bacteria or virus. The development of rapid point-of-care assays based on such algorithms could be clinically useful tools in the therapeutic decision-making.

Highlights

The correct diagnosis of acute infections as to bacteria, mycoplasma or virus is a clinical challenge and has a great impact on the therapeutic decision
The concentrations of P-Azurocidin, S-PCT, P-Human Neutrophil Lipocalin (HNL) Dimer and S-induced Protein 10 kDa (IP-10) were similar in serum/plasma from patients with viral or mycoplasma pneumoniae infections
In this report we show the results of nine different blood-based biomarkers and their capacity to distinguish mycoplasma pneumoniae pneumonia from lower respiratory tract infections caused by bacteria or virus

Summary

Introduction

The correct diagnosis of acute infections as to bacteria, mycoplasma or virus is a clinical challenge and has a great impact on the therapeutic decision. In our previous reports we showed that the measurement of HNL in serum or after in vitro activation is a powerful and accurate biomarker in the distinction between bacterial and viral infections (Venge et al, 2015a; Venge et al, 2019; Venge and Xu, 2019). The diagnostic distinction could be improved further by adding bio markers such as IP-10 or TRAIL to the diagnostic algorithm reaching sensitivities and specificities of between 90 and 95%.(Venge et al, 2019) The diagnosis of mycoplasma pneumoniae infections is fairly complicated and takes several hours to days and involves PCR and serology (Meyer Sauteur et al, 2019). In a recent report from the Bio-X cohort we showed that plasma levels of Calprotectin were elevated in patients with mycoplasma pneumoniae pneumonia and superior to Procalcitonin and Azurocidin as diagnostic biomarkers of the myco plasma pneumoniae infection and the distinction to viral respiratory infections (Havelka et al, 2020). HNL was measured in EDTA plasma by an HNL Dimer specific assay and after fMLP activation of neutrophils in whole blood

Objectives

Methods

Results

Conclusion