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ORIGINAL RESEARCH

The Value of Metagenomic Next-Generation Sequencing in Hematological Malignancy Patients with Febrile Neutropenia After Empiric Antibiotic Treatment Failure

, , , , , , , , & show all
Pages 3549-3559 | Published online: 07 Jul 2022
 

Abstract

Background

It was crucial to use empirical antibiotics in febrile neutropenia (FN) patients. However, most patients still died from infection due to poor efficacy. Metagenomic next-generation sequencing (mNGS) is a rapid microbiological diagnostic method. The value of mNGS in patients with FN remains to be studied, especially after empiric antibiotic treatment.

Methods

We retrospectively analyzed the differences between mNGS and the traditional methods in 192 patients with hematological malignancies who have received empiric antibiotic treatment. Samples were collected when patient had chills or half an hour before peak body temperature. And we compared the differences between FN and non-FN patients, mainly including types of pathogens and the diagnostic value of different pathogens.

Results

Despite receiving empirical treatment, the pathogen detection rate of mNGS was significantly higher than the traditional method (80.21% vs 25.00%, P<0.001). And it has obvious advantages in detecting mixed pathogens infection (80.21% vs 4.17%, P<0.001). Then, we found that mNGS saw more pathogens in the FN than in the non-FN group, especially fungus. 21/33 (63.63%) of FN patients was diagnosed with fungal infections. The fungal detection rate in FN was significantly higher than non-FN group (32.35% vs 12.22%, P=0.001). Besides, the sensitivity of mNGS was higher than the traditional methods in both FN and non-FN group (P<0.001), but no significant difference in specificity (P>0.05). In the FN group, empiric antibiotic treatment of 46/102 (45.10%) patients did not treat all the pathogens detected by mNGS. After adjusting the antimicrobial regimen according to the results of mNGS, the effective rate at 72 hours and 7 days was 22/46 (47.83%) and 24/102 (52.17%), respectively.

Conclusion

mNGS had a significant impact on the diagnosis of infection and the second-line antimicrobial therapy in FN. mNGS plays a more important role in FN patients, especially in the diagnosis of fungal infections.

Purpose

Firstly, we compared the difference between mNGS and the traditional methods in the diagnosis of infection. Secondly, we assessed the value of mNGS in FN patients by comparing it with non-FN patients, including types of pathogens and the diagnostic value of different pathogens. In order to show that mNGS plays a more important role in FN.

Abbreviations

FN, febrile neutropenia; mNGS, Metagenomic next generation sequencing; CMV, Human betaherpesvirus 5; BK, Human polyomavirus 1; HBV, Hepatitis B; EBV, Human gammaherpesvirus 4; PCR, polymerase chain reaction; PPV, positive predictive value; NPV, negative predictive value; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia.

Ethics Statement

The study was approved by the Ethics Committee of Tianjin First Central Hospital. The need for informed consent was waived due to the retrospective nature of the study and because the data were anonymously analyzed.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by grants from the General Project of National Natural Science Foundation of China (81970180 to MZ), and the Key Science and Technology Support Project of Tianjin Science and Technology Bureau (20YFZCSY00800 to MZ), as well as Tianjin Key Medical Discipline (Specialty) Construction Project.