Faster Diagnostic Insights for Neurologic Infections: How Next-Day NGS is Impacting Care

In neurologic infection cases, time determines patient outcomes. Delays in identifying the cause of infection can lead to extended ICU stays, major complications, or diminished quality of life for patients. Traditional culture methods can take days and sometimes weeks to yield results—time that neither physicians or their patients have.

Our integration of the Illumina MiSeq i100 Plus enables delivery of Next-Gen DNA Sequencing (NGS) results as soon as 24 hours after sample receipt. This advancement is providing neurologists and infectious disease specialists with insights when they need them most, reducing diagnostic delays.

By minimizing the time lag between testing and the start of treatment, providers can deescalate and rapidly shift away from empiric solutions to more targeted ones, diminishing the risk of complications and improving patient outcomes.

Challenges to Diagnosing Neurologic Infections

This quote from a study by F. Noorbaksh et al. describes the diagnostic challenge:

Infections of the human nervous system represent among the most challenging of all neurological diseases… Neurological infections lead to altered expression levels of a wide range of host- and pathogen-derived biomolecules both within and outside of the nervous system.

 

 

These molecular complexities underscore the limits of conventional testing. Culture can only grow an estimated 2% of bacterial species, leaving most organisms undetected. In fact, one comparative study of bacterial meningitis found that culture identified potential pathogens in only 17.5% of cerebrospinal fluid (CSF) samples, while a molecular test did the same for nearly 60% of them.

The limits of culture testing are even more pronounced with anaerobes. Organisms such as Prevotella and Bacteroides, both known causes of brain abscesses, often fail to grow in culture due to their slow growth and polymicrobial nature. Likewise, Cutibacterium acnes (C. acnes), the third most common cause of CSF shunt infections, is frequently missed because of its slow-growing, anaerobic nature and biofilm-associated behavior.

How NGS Overcomes These Limits

In pooled analyses of CNS infections, metagenomic NGS achieved a sensitivity of 77% and specificity of 96%, with an exceptional overall diagnostic accuracy of 91%. These results far surpass culture and further reinforced an internal validation of our own upgraded qPCR + NGS workflow, following our transition to the MiSeq i100 Plus sequencing platform.

MicroGenDX Targeted NGS Internal Validation Results

To overcome these diagnostic gaps, our laboratory combines qPCR and NGS to deliver faster, broader, and more actionable results in one streamlined diagnostic aid. Combined with qPCR enabled antimicrobial resistance gene testing, our lab delivers results rapidly with all the information needed to support data-driven clinical decision-making.

These internal validation results are backed by over a decade of collaboration with leading regulatory bodies. Our laboratory is certified under Clinical Laboratory Improvement Amendments (CLIA), accredited by the College of American Pathologists (CAP), and is the only NGS lab licensed by the New York State Department of Health through the Clinical Laboratory Evaluation Program (CLEP) – the most rigorous molecular diagnostics accreditation in the U.S.

These certifications ensure our laboratory workflows meet the highest standards for analytical validity, quality control, and clinical reliability. They are a critical prerequisite for hospital systems and providers seeking to confidently adopt NGS.

How Next-Day NGS from MicroGenDX Works

Once a specimen is received, MicroGenDX conducts both quantitative polymerase chain reaction (qPCR) and Next-Generation DNA Sequencing (NGS) analyses in an integrated process. qPCR provides rapid, extremely sensitive testing for specific pathogens and antibiotic resistance genes, while NGS delivers a broader, bias-free profile of any bacterial and fungal DNA present in a sample.

Utilizing both of these technologies gives providers a more complete view of the infection site than other tests, to better the provider’s diagnostic and treatment processes. All results come in one, easy-to-read report.

The process starts with DNA extraction, where microbial DNA is isolated from the patient sample. This step separates genetic material from proteins, host DNA, and other cellular debris in the sample, with high efficiency for downstream molecular analyses. The extracted DNA then undergoes Next-Generation Sequencing on the MiSeq i100 Plus, where millions of genetic fragments are read in parallel. Unlike culture, sequencing does not require organisms to grow in the lab.

Instead, NGS detects microbial DNA directly from aerobes, anaerobes, slow growers, mycobacteria, and viable but nonculturable pathogens (VNBC) that may otherwise be missed.

Once sequencing data is generated, a proprietary bioinformatic analysis compares each fragment to our database of over 60,000 bacteria and fungi. This enables species-level microbe identification.

In parallel, qPCR detects common pathogens and drug resistance genes, arming clinicians with actionable insight to guide treatment decisions.

The final step is to combine the qPCR + NGS results into one easy-to-read report. Providers will learn:

• the names of detected microbes (at the species level)
• relative abundance of each microbe
• what resistance genes are present
• a list of antimicrobials to consider for treatment

The list of antimicrobials and antifungals for consideration (based on research and the Sanford and Johns Hopkins Guides), supports physician with supplementary information as they prepare precision treatment.

With the addition of the i100 Plus, the entire NGS process has been accelerated. Time to results has dropped from an average of 3.5 days to as little as 24 hours after sample receipt with enhanced sequencing depth producing more reliable findings. In contrast, culture needs days to weeks and PCR panels need 24-48 hours to process while still missing many clinically relevant pathogens – potentially producing incomplete results.

Even when PCR panels are available in hospital labs with under 12 hour turnaround times, they are limited by target bias. These panels can only detect a number of targeted species, and even listed organisms may escape detection if there are mutations in the primer binding site. This is an issue across strains of many bacterial and fungal species. By combining qPCR with unbiased NGS, our testing provides broad detection and compensates for primer-dependent blind spots.

For neurologists and clinical teams, speed matters. Rapid turnaround supports timely treatment decisions without sacrificing accuracy or breadth when patient care is most critical. The ability to pivot from empiric coverage to targeted therapy so quickly marks a meaningful change in how CNS infections can be managed.

This shift from multi-day delayed diagnostics to real-time clinical insight isn’t theoretical, it’s already happening. The following two cases from infectious disease physician, Dr. Jason Sniffen at Advent Health Orlando show how rapid NGS results changed the course of care for patients with life-threatening neurological infections.

Case 1: Rapid Detection in a Life-Threatening CNS Infection

A patient with a brain bleed and infected aneurysm needed an external ventricular drain (EVD) inserted to relieve pressure. MicroGenDX received samples of the patient’s cerebrospinal fluid (CSF) and processed it for qPCR + NGS testing.
Within 24 hours, NGS tests identified Bacillus cereus and Campylobacter jejuni. Neither pathogen was covered by the empiric treatment regimen.

According to Dr. Sniffen:

[Initially,] I was not treating for the detected bacteria, and [the initial] antibiotics don’t cover it. This truly made a difference in his care.

Armed with rapid, accurate pathogen detection, he was able to personalize therapy accordingly. The patient went on to make a full recovery. Dr. Sniffen emphasized that the speed of results was critical, praising the new turnaround time as “the bomb.”

He also noted the cross-specialty utility of NGS, with applications beyond neurology since the method can be performed on virtually any bodily fluid or tissue, covering nearly everything from bronchoalveolar lavage (BAL) samples to tissue and urine samples.

Nick Sanford, PhD, Vice President of Medical Affairs at MicroGenDX, notes that Bacillus cereus produces toxins that damage tissues and weaken the immune system, so the pathogen can spread within a patient’s central nervous system (CNS)–carrying a significant mortality risk.

Similarly, pathogens such as Campylobacter jejuni can evade immune detection and also cause persistent or acute inflammation in the CNS, underscoring the need for a rapid and accurate diagnosis.

Case 2: Neurosurgical Infection and Early Antimicrobial Optimization

In another case, a 51-year-old woman developed wound drainage several weeks after bifrontal craniotomy for tumor resection. An MRI confirmed epidural empyema, and the patient required a bicoronal craniectomy with abscess evacuation. This time-sensitive situation warranted rapid testing to help treat the patient.

NGS testing uncovered C. acnes in just 24 hours, compared to the five days required for culture. Sanford says that C. acnes is a slow-growing pathogen that can complicate neurosurgical infections. “Because it takes so long to culture, clinicians often have to treat broadly while they wait, even though such therapy can be suboptimal,” he noted.

“Next-day NGS eliminates that uncertainty, delivering results early enough to help physicians tailor antibiotics appropriately; preventing lasting brain damage in critical cases like this.”

This rapid molecular detection supported a targeted treatment plan, appropriate for the patient’s infection.

Bringing the Clinical Benefits of NGS to Your Patients

Neurological infections are high-stakes, often involve elusive pathogens, and may worsen with sustained broad-spectrum, empiric treatments.

With a 15-year strong, CAP-validated accuracy of 99.2%, MicroGenDX is proud to provide physicians with the speed and clinical clarity necessary to treat with confidence.

MicroGenDX testing helps hospitals reduce time on empiric therapy, minimize complication risk, shorten ICU stays, and lower readmission rates. It also equips care teams with faster, more definitive results that enable well-informed diagnoses and treatment decisions, improving patient care management.

As Dr. Sniffen observed, rapid sequencing can be performed on virtually any specimen type. This is why MicroGenDX offers 20 different qPCR+NGS tests, covering specialties from wound care to women’s health.

But in neurology and neurosurgery, where the longer the diagnostic delay, the greater the life-altering consequences, the ability to obtain clear insights faster makes the most immediate difference.

Interested in bringing next-day NGS to your practice or hospital system?

Our team can walk you through testing options, sample collection, and any questions you have:

Call us at 1-855-208-0019 or email us at [email protected] to learn more.