Role and Clinical Application of Metagenomic Next-Generation Sequencing in Immunocompromised Patients With Acute Respiratory Failure During Veno-Venous Extracorporeal Membrane Oxygenation

Abstract

Objectives: There are few studies of metagenomic next-generation sequencing (mNGS) in immunocompromised patients assisted by veno-venous extracorporeal membrane oxygenation (vv-ECMO). The present study is aimed to investigate the pathogen-detected effect and clinical therapy value of mNGS technologies in immunocompromised patients assisted by vv-ECMO.

Methods: Our study retrospectively enrolled 46 immunocompromised patients supported by vv-ECMO from Jan 2017 to June 2021 at the First Affiliated Hospital of Zhengzhou University, respectively. Patients were divided into the deterioration group (Group D) (n = 31) and improvement group (Group I) (n = 15) according to their outcomes. Baseline characteristics and etiological data of patients during hospitalization of 2 groups were compared. The pathogens detected by mNGS and antibiotic regimens guided by mNGS in immunocompromised patients assisted by vv-ECMO were analyzed.

Results: Compared with Group I, the deterioration patients showed a higher percentage of chronic obstructive pulmonary disease (COPD) (32.3% vs. 6.7%, p < 0.01) and were significantly older (47.77 ± 16.72 years vs. 32 ± 15.05 years, p < 0.01). Within 48 h of being ECMO assisted, the consistency of the samples detected by traditional culture and mNGS at the same time was good (traditional culture vs. mNGS detection, the positive rate of bronchoalveolar lavage fluid (BALF) culture: 26.1% vs. 30.4%; the positive rate of blood sample culture: 12.2% vs. 12.2%, p > 0.05). However, mNGS detected far more pathogen species and strains than conventional culture (30 strains vs. 78 strains, p < 0.01); the most popular pathogen was Klebsiella pneumoniae. Parts of patients had their antibiotic treatment adjustments, and the improvement patients showed less usage of broad-spectrum antibiotics.

Conclusions: mNGS may play a relatively important role in detecting mixed pathogens and personalized antibiotic treatment in immunocompromised patients assisted by vv-ECMO.

Keywords: antibiotic treatment; extracorporeal membrane oxygenation; immunocompromised patients; metagenomic next-generation sequencing; routine test.

Figure 1

The flowchart.

Figure 2

Circle chart of statistics on the number of patients detected by mNGS and conventional technology. The patients were divided into five groups for statistics: the number of positive patients only by routine test, the number of positive patients only by mNGS test, the number of positive patients by routine test and mNGS test, the number of negative patients by mNGS test, and the number of negative patients by routine test. mNGS, metagenomic next-generation sequencing.

Figure 3

The heatmap of the pathogen species and strains detected by mNGS (within 48 h after ECMO) or routine test (24 h before and within 48 h after ECMO). The value of each pathogen represents the number of times detected in this group; after log10 conversion, the value is used for visual display. The pathogen was divided into five categories: G+ (Gram-positive bacteria), G− (Gram-negative bacteria), fungus, virus, and special pathogen. Patients of each group were tested for blood and BALF (bronchoalveolar lavage fluid) by mNGS or routine test. mNGS, metagenomic next-generation sequencing; ECMO, extracorporeal membrane oxygenation.

Figure 4

The antibiotic usage of patients. (A) The use of antibiotics before being assisted by the ECMO. (B) The use of antibiotics after ECMO was removed. The heatmaps were drawn using log10 (days of drug treatment), and all of the drugs were divided into eight categories according to their function. NA, no clear classification; ECMO, extracorporeal membrane oxygenation.