Antibiotic overuse is a real issue. In modern countries, despite obsessing over antibiotic stewardship, we are still suckers for the excessive use of both narrow-spectrum antibiotics for ambulatory patients and broad-spectrum antibiotics for the critically ill. In less resource-capable areas, the tests used to stratify patients as potentially bacterial or viral exceed the cost of the antibiotics – also leading down the path to overuse.
This breathless coverage, featured in Time, the AFP, and proudly advertised by Stanford Medicine, profiles a new panel of tests that is destined to bring clarity. Rather than relying simply on a single biomarker, “our test can detect an infection anywhere in the body by ‘reading the immune system’”.
They used retrospective genetic expression cohorts from children and adults with supposedly confirmed non-infectious or infectious etiologies to derive and validate a scoring system to differentiate the underlying cause of sepsis. They then further trim their model by eliminating infants and predominately healthy patients from outpatient cohorts. Ultimately, they then test their model on a previously uncharacterized whole blood sample from 96 pediatric sepsis patients and report an AUC for viral vs. bacterial sepsis of 0.84, with a -LR of 0.15 and +LR of 3.0 for bacterial infections. At face value, translated to a presumed clinical setting with a generally low prevalence of bacterial infection complicating SIRS, this is an uninspiring result.
However, these authors rather focus their discussion and press releases around the -LR of 0.10 and +LR of 2.34 produced as part of their ideal validation cohort, trumpeting its superiority over the -LR for procalcitonin of 0.29 as “three-fold improvement”. This is, of course, nonsense, as the AUC from that same procalcitonin meta-analysis was 0.85, and these authors are simply cherry-picking one threshold and performance characteristic for their comparison.
Now, that’s hardly to say this is not novel work, and their confusion matrices showing clustering of non-infected SIRS vs. bacterial sepsis vs. viral sepsis are quite lovely. Their approach is interesting, and very well could ultimately outperform existing strategies. However, their current performance clearly does not match the hype, and they are miles away from a meaningful validation. Furthermore, the sort of nano-array assay required is neither fast enough to be clinically useful nor likely to be produced cheaply enough to be used in some of the resource-poor settings they claim to be addressing.
It makes for a nice headline, but it’s better consigned to the “Fantasy/Science Fiction” shelf of your local bookstore for now.
“Robust classification of bacterial and viral infections via integrated host gene expression diagnostics”
http://stm.sciencemag.org/content/8/346/346ra91