A recent study published in the Open Forum Infectious Diseases Journal examined the role of plasma metagenomic next-generation sequencing (mNGS), a promising method for detecting infectious illnesses.
Study: Impact of metagenomic next-generation sequencing of plasma cell-free DNA testing in the management of patients with suspected infectious diseases. Image Credit: ArtemisDiana/Shutterstock.com
Background
The ability to rapidly identify human pathogens in clinical samples has improved due to developments in diagnostic technology for infectious diseases, such as automated methods for microbial identification and matrix-assisted laser desorption ionization-time of flight.
However, these procedures necessitate culture growth; thus, detecting cases where infected material is unavailable, or the etiologic agent cannot be grown in a lab is challenging.
mNGS uses high-throughput sequencing technologies to identify DNA or RNA from suspected pathogens quickly and precisely. NGS can be applied to any patient sample, but microbial cell-free DNA (mcf-DNA) is used for readily obtained samples like patient serum.
Mcf-DNA is released by deceased and dying cells, and fragments of genomic DNA from pathogenic organisms have been isolated in mcf-DNA from patients with active infections.
In January 2021, the present research team began providing mNGS of mcf-DNA to determine the clinical relevance of plasma mcf-DNA mNGS testing in managing patients with suspected infectious diseases.
About the study
This retrospective study analyzed adult patients who underwent mNGS testing as part of their clinical therapy at the University of Michigan-affiliated Michigan Medicine (MM). The study used the Electronic Medical Record Search Engine (EMERSE) to identify all patients who underwent mNGS plasma testing between 1/1/2021 and 7/25/22.
A medical record review yielded demographic data, mNGS testing date, rationale and results, additional relevant infectious disease workup, and the final diagnosis and treatment.
The examination date has been defined as the date that mNGS testing was scheduled in the electronic medical record. The testing date was collated with the completion date of the standard infectious disease (ID) workup. The workup includes culture incubation, serologic tests, and cross-sectional imaging.
The clinical impact of mNGS test results was assessed based on medical judgments and interpretations. If the results changed the initial antimicrobial medication regimen or time frame suggested by the treating physician, it impacted clinical care.
If the initial antibiotic plan was not altered, the final diagnosis was made before the mNGS result returned, and the patient passed away or was enrolled in hospice before the result was available for interpretation.
Definitive diagnoses were made using all the findings from tests and an ongoing evaluation of the patient's medical history. The descriptive analysis of variables, the t-test, and the Fisher exact test were used to identify group differences.
Results
A study of 69 patients with immunocompromised (IC) conditions found that 63% of mNGS tests were positive, with 31% having clinical effects. Only 15% of the tests had an effect on the decisions regarding antibiotic treatment.
Only one-quarter of the mNGS tests exhibited any clinical significance. There was no statistically significant difference in the number of clinically relevant tests performed on IC patients.
In a medical center, commercial serum mNGS test results had little impact on patient management, with only 25% of patients having clinically significant results.
Plasma mNGS testing may help diagnose infections in IC hosts with impaired T-cell response, improving antibiotic management by 47–61% in febrile neutropenia patients, 53% in adults with hematological malignancies and stem cell transplant recipients, and 45% in solid organ transplant recipients.
However, due to the underrepresentation of IC in the patient cohort, mNGS test results had no clinical impact on the study.
In patients with culture-negative endocarditis or endovascular infection, plasma mNGS test results were more useful in clinical decision-making. However, plasma mNGS is not widely used to diagnose culture-negative endocarditis; direct comparisons between mNGS and standard serologic testing are lacking.
The clinical performance of plasma mNGS is also unstudied, and prospective studies are needed to compare it to standard-of-care diagnosis tools. Understanding plasma mNGS diagnostic performance in various clinical contexts and patient populations will help define its role and use in clinical practice.
Limitations and conclusion
This study has limitations such as a retrospective design, a single-center review, and a small sample size. A larger sample or a larger proportion of patients with specific infections could better assess the impact of mNGS.
Patient selection, timing, and inter-provider ordering practices may also affect patient management. The study evaluates local order practices and their clinical impact on patient management.
Before extensively using this testing method, the findings highlight the need for additional research, particularly prospective research that includes negative controls. Further studies are needed before the widespread adoption of mNGS is considered a standard of care.
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