WBCs? Glucose? Gram stain? Next-generation genetic sequencing?
It’s the NEJM again, so you know the fingerprints of financial and professional conflict of interest pervade, but this study is still fairly typical of the types of infectious disease diagnostics on the horizon. Why wait for any specific organism to grow – over the course of days – when you can simply try and match DNA fragments floating around to those of various viral and bacterial pathogens?
The promise probably doesn’t quite meet the hype in this study, based out of UCSF, where many of those working on the project hold shares of the patent on the technology. In this prospective multicenter study, these authors recruited patients, ostensibly, who were diagnostic challenges – “idiopathic meningitis, encephalitis, or myelitis in patients who had not received a diagnosis at the time of enrollment”. The vast majority of those enrolled were ultimately encephalitis and meningitis. Then, this wasn’t specifically a formal trial as much as it was a collected case series with a 1-year convenience time frame, constrained by funding and testing capacity.
The authors screened 482 patients for a final study population of 204. Of these 204, their next-generation sequencing methods made a diagnosis in 32. Of these 32, 19 had already been made by further directed clinical evaluation. Of those final 13, then, in which the NGS assay was the only method of diagnosis, this information augmented clinical management in 7. The supplementary appendix details these specific impacts on management – although, in reality, few of the vignettes are terribly compelling. A handful of cases confirmed a suspected diagnosis, leading to clinicians to narrow antibiotic or antifungal therapy, while others “reassured” clinicians they were on the right course. The NGS assay did, however, occasionally detect clinically important pathogens and guide directed treatment, including Nocardia and S. mitis meningitis whose conventional testing was otherwise negative. Unfortunately, despite the addition of this testing, no conclusive final diagnosis was ever made in half their cohort.
At present, this sort of testing is not likely to be within the scope of the Emergency Department – these represent complex cases with low diagnostic yield, and even while this method picks up some new diagnoses, it also misses others established by conventional means. That said, this sort of technology will likely yet only improve, decrease in cost, and additional applications will edge closer to mainstream care.
“Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis”