What is the role of the Karius test in diagnosing infections?

From the Guidelines

The Karius test is a non-invasive diagnostic tool that utilizes next-generation sequencing to detect cell-free microbial DNA in plasma samples, allowing for the identification of various pathogens, including bacteria, fungi, and viruses, with high sensitivity and species-level identification 1. The Karius test serves as a valuable alternative to traditional culture methods, particularly beneficial for diagnosing difficult-to-culture organisms, deep-seated infections, or cases where antimicrobial therapy has already been initiated. Some key advantages of the Karius test include:

• Non-invasive, requiring only a blood draw
• Rapid results, typically within a short turnaround time
• Ability to detect a wide range of pathogens, including those that are difficult to culture
• High sensitivity and species-level identification, crucial for guiding targeted therapy However, it is essential to note that the Karius test has limitations, such as only detecting DNA microbes and having limited use in clinical laboratories due to these restrictions 1. The test works by isolating microbial DNA fragments that circulate in the bloodstream after being released from infection sites, then using sophisticated bioinformatics to identify specific pathogens. While it offers advantages in speed and comprehensive pathogen detection, the Karius test should be used as a complementary tool alongside traditional diagnostic methods rather than as a complete replacement, as it may detect colonizing organisms or contaminants that aren't causing active infection. In clinical practice, the Karius test can be particularly useful in immunocompromised patients, those with suspected endocarditis, complicated pneumonia, or infections of unknown origin, where rapid and accurate diagnosis is critical for guiding treatment and improving patient outcomes 1.

From the Research

Overview of the Karius Test

• The Karius test is a microbial cell-free DNA sequencing test that identifies and quantifies microbial cell-free DNA in plasma from a wide range of bacteria, DNA viruses, fungi, and eukaryotic parasites 2.
• The test has been validated analytically and clinically, showing 93.7% agreement with blood culture in a cohort of patients with a sepsis alert 2.

Role in Diagnosing Infections

• The Karius test has the potential to improve diagnostic evaluation of infectious diseases, particularly in cases where standard testing fails to identify a pathogen 3, 4, 5.
• The test can detect a broad spectrum of pathogens, including opportunistic fungi, zoonotic and vector-borne pathogens, and diagnostically challenging pathogens 6.
• Studies have shown that the Karius test can lead to positive impact in patient management, particularly in cases where the test results lead to the identification of a specific pathogen and subsequent targeted treatment 3, 5.

Clinical Impact

• The clinical impact of the Karius test has been evaluated in several studies, with varying results 3, 4, 5.
• One study found that the test had a positive impact in 7.3% of cases, a negative impact in 3.7% of cases, and no impact in 86.6% of cases 4.
• Another study found that the test had a positive impact in 30.4% of cases, a negative impact in 2.2% of cases, and no impact in 65.2% of cases 3.
• The test has been shown to be particularly useful in the diagnosis and management of febrile neutropenia, with a sensitivity of 85% and specificity of 100% 5.

Limitations and Future Directions

• The Karius test is not without limitations, and further studies are needed to identify high-yield patient populations and define the complementary role of the test to conventional microbiological methods 4.
• Additionally, the test requires careful interpretation of results, as polybacterial results can be challenging to interpret and may have limited clinical impact 3.