Metagenomic Next-Generation Sequencing Successfully Detects Pulmonary Infectious Pathogens in Children With Hematologic Malignancy

Abstract

Background: Pulmonary infection is a leading cause of mortality in pediatric patients with hematologic malignancy (HM). In clinical settings, pulmonary pathogens are frequently undetectable, and empiric therapies may be costly, ineffective and lead to poor outcomes in this vulnerable population. Metagenomic next-generation sequencing (mNGS) enhances pathogen detection, but data on its application in pediatric patients with HM and pulmonary infections are scarce.

Methods: We retrospectively reviewed 55 pediatric patients with HM and pulmonary infection who were performed mNGS on bronchoalveolar lavage fluid from January 2020 to October 2021. The performances of mNGS methods and conventional microbiological methods in pathogenic diagnosis and subsequently antibiotic adjustment were investigated.

Results: A definite or probable microbial etiology of pulmonary infection was established for 50 of the 55 patients (90.9%) when mNGS was combined with conventional microbiological tests. The positive rate was 87.3% (48 of 55 patients) for mNGS versus 34.5% (19 of 55 patients) with conventional microbiological methods (P < 0.001). Bacteria, viruses and fungi were detected in 17/55 (30.9%), 25/55 (45.5%) and 19/55 (34.5%) cases using mNGS, respectively. Furthermore, 17 patients (30.9%) were identified as pulmonary mixed infections. Among the 50 pathogen-positive cases, 38% (19/50) were not completely pathogen-covered by empirical antibiotics and all of them were accordingly made an antibiotic adjustment. In the present study, the 30-day mortality rate was 7.3%.

Conclusion: mNGS is a valuable diagnostic tool to determine the etiology and appropriate treatment in pediatric patients with HM and pulmonary infection. In these vulnerable children with HM, pulmonary infections are life-threatening, so we recommend that mNGS should be considered as a front-line diagnostic test.

Keywords: children; diagnosis; hematologic malignancy; mNGS; pulmonary infection.

Figure 1

(A, B) Distribution of pathogens detected by mNGS and conventional methods. S. pneumoniae, Streptococcus pneumoniae; H. influenzae, Haemophilus influenzae; S. aureus, Staphylococcus aureus; E. coli, Escherichia coli; E. meningospetica, Elizabethkingia meningospetica; M. catarrhalis, Moraxella catarrhalis; E. faecalis, Enterococcus faecalis; S. haemolyticus, Staphylococcus haemolyticus; E. faecium, Enterococcus faecium; A. baumannii, Acinetobacter baumannii; B. multivorans, Burkholderia multivorans; CMV, cytomegalovirus; RSV, Respiratory syncytial virus; HPIV 3, Human parainfluenza 3 virus; HMPV, Human metapneumovirus; HPV 3, Human polyomavirus 3; EBV, Epstein-Barr virus; HRV A, Rhinovirus A; TTV, Torque teno virus; HHV 6B, Human betaherpesvirus 6B; HHV 7, Human betaherpesvirus 7; P. jirovecii, Pneumocystis jirovecii; A. fumigatus, Aspergillus fumigatus; A. flavus, Aspergillus flavus; R. oryzae, Rhizopus oryzae; R. pusillus, Rhizomucor pusillus; A. niger, Aspergillus niger; MP, Mycoplasma pneumonia.

Figure 2

Percentage of patients with mixed infection for various pathogens. MP, Mycoplasma pneumonia.

Figure 3

The coverage and adjustment of antibiotics in the patients with pathogen positive pneumonia. (A) Among the patients with pathogen positive pneumonia, complete antibiotic coverage was 31 (62%); partial coverage was 5 (10%); and no coverage was 14 (28%). (B) Antibiotics were adjusted for 12 completely covered, and for all partly covered and uncovered patients.