Rapid Etiological Detection Value of Metagenomic Next-Generation Sequencing for Bloodstream Infections in Patients with High-Risk Hematologic Malignancies

Background: Patients with hematological malignancies often suffer from infectious fever, rapid and accurate diagnosis of pathogens facilitates optimal and precise treatment of infectious diseases. In recent years, metagenomic next-generation sequencing (mNGS) technology has been widely used in the etiological detection of patients with respiratory tract infection, sepsis, etc, due to its advantages of rapid detection.However, at present, the clinical diagnosis of mNGS in patients with hematological malignancies in secondary bloodstream infections remains scarce.

Objective: In this study, the application value of mNGS in the rapid etiological detection of bloodstream infection pathogens in patients with high-risk hematological malignancies was explored by comparing two etiological detection methods of mNGS and traditional pathogen culture.

Methods: This study retrospectively analyzed 66 peripheral blood samples of patients with high-risk hematologic malignancies in our hospital from May 2020 to January 2022. SPSS 20.0 software was used to analyze the positive rate, species distribution and consistency of pathogens between mNGS and traditional pathogen culture method. The diagnostic efficiency of the two etiological detection methods was compared, and the risk factors affecting the positive rate of mNGS were investigated.

Results: A total of 66 patients were enrolled in this study, including 38 males and 28 females, with an average age of (43.39±14.427) years. Among the 66 patients, 48 cases were acute myeloid leukemia (48/66, 72.7%), the rest included 2 cases of acute lymphoblastic leukemia (2/66, 3.0%), 3 cases of chronic myeloid leukemia (3/66, 4.5%), 3 cases of myelodysplastic syndrome (3/66, 4.5%), 4 cases of non-Hodgkin lymphoma (4/66, 6.0%), 4 cases of malignant tumor after autologous hematopoietic stem cell transplantation (4/66, 6.0%), and Hemophagocytic syndrome was found in 2 cases (2/66, 3.0%). Peripheral blood samples from 66 patients were both tested for mNGS and traditional pathogen culture. The positive rate of mNGS was 54.5% (36/66), while the traditional culture was 18.1% (12/66). There was a significant statistical difference between the two methods (P=0.000). Multivariate analysis was conducted on the influence of factors such as patient age, gender, disease diagnosis, and time from fever to the mNGS detection, and no statistical difference was found. Among the 36 mNGS-positive patients, a total of 64 pathogens were detected, including 19 bacteria (19/64, 29.7%), 12 fungus (12/64, 18.8%), 31 virus (31/64, 48.4%), and 2 special pathogens (2/64, 3.1%). Six drug-resistant bacteria were detected by mNGS in 5 patients .Among the 12 patients with positive traditional culture, 15 pathogens were detected, including 14 bacteria (14/15, 93.3%) and 1 fungus (1/12, 3.7%). In this study, 8 patients (8/66, 36.4%) were both positive for mNGS and traditional culture tests, and 5 of them (5/8, 62.5%) developed the same type of clinical infection with all or part identical detected pathogens. The time for positive and negative blood culture report was 72h and 7 days respectively, and 24h for mNGS. Among the 54 patients with negative results of traditional culture, 28 cases (28/54, 51.9%) were positive for mNGS, of which 15 cases (15/28, 53.6%) were made corresponding anti-infection regimens according to the positive results of mNGS, and the clinical efficacy was significantly improved. Seven of the 26 patients with both negative traditional culture and mNGS results were considered to have fungal infection based on chest imaging. After empirical antifungal treatment, the imaging results and clinical symptoms were improved; while only 4 of the remaining 19 patients (4/19, 21.5%) had clinical benefit from empirical anti-infective therapy. It demonstrated that pathogen-oriented therapy was significantly better than empirical anti-infective therapy (P=0.000).

Conclusions: mNGS enhanced the positive rate of bloodstream pathogens detection and provided more accurate pathogen species in patients with high-risk hematologic malignancies.It could effectively detect multidrug-resistant bacteria and special pathogens,which provide an important reference for clinical antimicrobial treatment and improved their prognosis.

No relevant conflicts of interest to declare.