I had the honor and pleasure of attending a Wellcome Trust
meeting for the last few days looking at the medical need and potential utility
of approaches to the rapid diagnosis of bacterial infection. The Trust gathered a very diverse group of
experts ranging from patient advocates to general practice physicians to
emergency room physicians to infectious disease specialists. The general
question was – could rapid diagnostic technologies be useful in the more
rational and appropriate treatment of patients with various infections. I think the general hypothesis was – if we can
provide a specific and reliable rapid diagnosis, we might be able to decrease
the empiric use of broad-spectrum antibiotics or at least de-escalate to more
specific therapy more quickly.
The first question that was posed was – what diagnostics do
we need? One fascinating and eye-opening observation (for me) was a clear
consensus that we need a rapid and reliable approach, probably focusing on the
host response, to distinguish bacterial from viral infection or even between
colonization and infection. The idea here would be to document that an
antibiotic is not needed and prevent unnecessary therapy. For most participants it was clear that for relatively mild
or self limited infections – e.g. sinusitis – we probably do not need such
tools. The idea here is that most
infections are viral and even those that are caused by bacteria, for the most
part, seem to go away without therapy.
Obviously, the question of whether treatment could actually shorten the
disease if only we could determine who to treat remains open. But the consensus was that this was not the
place where we should invest our diagnostic development efforts.
We then explored hospital-acquired pneumonia and ventilator-associated
pneumonia (HAP, VAP). There was
universal disbelief, condemnation or scorn for the current US approach to the
reporting of VAP using the new CDC criteria.
In the CDC approach, the diagnosis requires bronchoscopy and many
centers, like the one where I work, do not routinely do this procedure to make
the diagnosis. Therefore, we will never
report a single case. In addition, there is an active disincentive to make the
diagnosis given the potential for loss of reimbursement by payers. But VAP was
an infection where the consensus was that, again, some measure of whether the
patient was actually infected using host-response measures combined with a
rapid bacterial diagnostic directly on respiratory secretions would be useful
to guide initial therapy. Or, if it
could not be rapid enough for a very sick patent, such a diagnostic could guide
de-escalation over the ensuing 24 hours or so.
A side discussion emphasized the difficulty in carrying out
trials in VAP. There was the suggestion
that the current approach using non-inferiority is becoming infeasible and that
new trial designs are desperately needed.
HAP was a completely different story, though. Here, the
major problem was that, like community-acquired pneumonia, adequate specimens
to be used for a bacteriological diagnosis are only very rarely obtained – the
estimate was that such a specimen was available in only ~ 5% of cases. Therefore,
a rapid diagnosis of bacterial etiology could also not be performed. We did agree that again, some sort of test
looking at host response might be helpful to reassure us that at least the
patient in question had an actual bacterial infection.
Perhaps the most straightforward question we tackled was
complicated urinary tract infection. But
even here, some measure of local urinary tract inflammatory response was deemed
to be potentially useful to help sort out whether the bacteria and white cells
in the urine of a catheterized (or even not catheterized) elderly patient with
non-specific symptoms actually represent infection vs. colonization. Once this
was established, then a rapid bacterial diagnosis including an indication of
susceptibility was considered to be very useful in guiding initial therapy.
So the surprise, and perhaps I should not be surprised, was
the importance placed on the potential utility of using the host response to
distinguish bacterial infection from either colonization or from viral infection.
But, to my knowledge, this would still require vast amounts of research to
discover such biomarkers and validate them in various clinical settings. So, our
greatest desire is for something that will not exist for years to come. The utility, and even the potential utility,
of rapid diagnostics for limiting empiric therapy remains elusive for many infections
treated in hospital.
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