A lot of antibiotics get prescribed from the ER. And unfortunately, a lot of antibiotics get prescribed inappropriately there. That's the take home from a report by Donnelly et al in AAC this month.
Over 12M Americans visit the ER for acute respiratory infections every year, and about 60% leave with a prescription for antibiotics. This number has decreased only slightly in the last decade, from 62% to 58%, despite increased stewardship efforts.
The key parameter is how many of these patients got antibiotics who should not have, and here the numbers are discouraging: about 48% of patients not diagnosed with a bacterial infection still got antibiotics.
It's not too hard to understand why this happens, especially given the transient nature of the doctor-patient relationship in the ER setting. But that's a lot of antibiotics to be challenging our collective microbiomes with, and almost certainly a major driver of the spread of antibiotic resistance.
More education seems unlikely to help, and requiring pharmacist or ID doc sign off for prescribing seems unrealistic for ER care. The ideal solution would be a rapid test that distinguishes bacterial from viral infections.
Given that there are hundreds of potential pathogens for respiratory infections, the strategy for developing a viral vs bacterial test can't be based on pathogen detection. Instead, this test would take advantage of the differential response of our immune systems to bacterial vs viral infections.
One such test already exists, the procalcitonin test. PCT is a mediator of cytokine responses, the molecules which different cell types in the immune system use to communicate and coordinate their responses to infection. PCT levels rise in response to bacterial but not viral infections. The availability of PCT assays in the ER has been shown to reduce excessive antibiotic use by 30-80%. Unfortunately PCT has some limitations as a biomarker - its levels rise in response to a number of shock states, not just bacterial infections.
It is unlikely that PCT or any other single biomarker will serve to adequately distinguish bacterial from viral infections. However, a couple of studies (here and here)have shown that arrays of biomarkers - some 15 to 30 in all - collectively perform quite well at this task.
So the concept of a bacterial-viral test is sound, but the path to execution is not yet obvious. The vast majority of diagnostic assays measure a single analyte. There are a few multiplexed assays for bacterial identification and resistance gene detection, such as the Cepheid Xpert or the Nanosphere Verigene systems. But the genes of immune cells don't vary in response to infection - it is the pattern of mRNA and protein expression that changes. Neither the Cepheid or Nanosphere systems currently measures mRNA levels, and therefore some serious product development would be required for either of these platforms.
For detection of protein expression, the only multiplex platforms are mass spectrometry and the SomaLogic SomaScan system. Sample prep is always the Achilles heel of mass spec - the amount of sample cleanup required to get a good signal makes it a poor platform for a rapid test. The SomaScan system is currently configured only as a lab-developed test that takes a couple of days to return results. It could potentially be developed into an IVD platform, but that hasn't happened yet.
So there is a significant opportunity here - urgent unmet clinical need, much wasteful spending, very large markets. Is anyone up to the challenge?
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