On the other hand...

I've been pretty critical of hospitals' reluctance to make use of rapid diagnostics to improve patient care. And I think that this criticism has been well-deserved. But these tests do have some shortcomings, and it's only fair to take note of them.

Limited reportable results. Most rapid tests only identify a single organism. An exception is the Verigene Gram-positive Blood Culture Test, which returns ID results for 9 species. Limited results mean that labs still have to do a full workup in order to identify organisms not covered by the rapid test. Rapid testing therefore doesn't replace any test; instead it adds to workload and cost.

Resistance but not susceptibility. Rapid tests, with one exception, detect sequences or products from resistance genes such as mecA or vanA/B. A positive result thus (usually but not always) indicates a resistant phenotype. But when resistance rates are at 30% or 40% or even more, doctors tend to presume resistance and prescribe accordingly before receiving test results. Thus the clinical value of a positive result for resistance is somewhat limited - the patient is likely already on the antibiotic indicated by the test as being appropriate. And then, a negative result for a resistance gene is just that - it means a certain gene (actually just a small target segment of it) is missing or altered, but it does not necessarily follow that the organism will be susceptible to the antibiotic in question. Of the rapid tests, only the MicroPhage test was cleared to return a susceptibility result which would enable a change in therapy. And it is no longer available.

So there are some legitimate reasons to hold off on adoption of rapid testing. But they still are outweighed by the benefits to the patient, and to the healthcare system as a whole. You don't have to save many ICU days to pay for a whole lot of testing. But the savings are often diffuse and indirect and accrue to payors outside the hospital, while the costs are borne by the lab making the purchasing decision. Viewed from this perspective, it's not hard to see why adoption of rapid testing has been so slow.

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What the CDC report didn't say

Judging from the number of Google alerts hitting my inbox, pretty much everyone who blogs in the healthcare space is writing about the CDC report on the threat of antibiotic resistance. Most of this writing is superficial regurgitation of the headline numbers, and is not really very interesting. The report itself is a nice resource that collects a lot of existing data in one place and makes it accessible to the general public, but does not contain any surprises or revelations.

The report rightfully calls for development of new antibiotics and rapid diagnostics to contain the threat. David Shlaes has posted a nice analysis of the short-sighted and flawed thinking at large pharma companies that holds back antibiotic development efforts.

A different, but no less crippling dynamic holds back the development of rapid diagnostics. As I've written before (here and here), the incentives for rapid diagnostics for antibiotic resistance and susceptibility determinations are misaligned, if not lacking altogether. Patients would benefit from their use, but no one in the hospital has a compelling reason to adopt these tests, which do tend to be pricey by the standards of microbiology. That is, they cost more than a Petri dish or a tube of rabbit plasma.

Hospital microbiology labs have to purchase the tests out of budgets that are always under pressure, given their status as cost centers rather than revenue generators. Micro labs in turn bear no responsibility when patients are prescribed inappropriate empirical antibiotics; they get no reward when an inappropriate prescription is avoided, even though this can result in considerable savings.

A well-respected clinical microbiologist once remarked to me that what MicroPhage really needed was for a patients' family to sue a hospital for not using our test, leading the patient to die while on ineffective antibiotics. He imagined the courtroom scene: "You mean that you left the patient on wrong antibiotics for 3 days because you didn't want to spend $50?" The thought of a penny pinching hospital admin squirming on the stand clearly intrigued him.

The unfortunate thing about this situation is that there is, I think, considerable willingness to pay to get it right. We just don't ask the right people - that is, the patients. I visited Shanghai in 2011 to get a sense of whether China might be a potential market for our test. Remarkably for a nominally socialist country, there is no system of socialized medicine, nor is insurance common. Patients pay out of pocket for care, which is one explanation for why their savings rate is so high. I asked ID docs at local hospitals to explain who would order our test and how would it be paid for. They replied that they would go to the patient or their family, tell them that there was a test that would help guide treatment, and ask if the family was willing to pay for it. They were pretty sure the answer would usually be yes, even at the US price of $50.

And I suspect that most families of American patients with S. aureus bacteremia, which has a mortality rate of some 30%, would give the same answer. But nobody is asking them.

Until that changes, or until hospitals start getting sued for inappropriate antibiotic use, the return on investment for developing rapid antibiotic susceptibility tests will remain questionable.

 

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MDs playing lab tech?

David Shlaes is lamenting the passing of the good old days, when clinicians ran diagnostic tests right there in the ward. Gram stains, differential culture - the whole shebang. Even collected specimens themselves, they did. I'm sure this was great fun, and there is certainly value in having MDs get a little hands-on experience, if only to gain an appreciation of what can go wrong.

David is a smart guy, and knows way more about antibiotics than I will ever hope to - but this is plainly silly. There may be some overlap between doctoring skills and lab skills, but it is pretty slight, in my experience. There are very few MDs (usually MD-PhDs) I've met that I would want to have working in my lab. Not because they weren't smart enough, but because they weren't skeptical enough of their own genius to repeat "interesting" results over and over to see if they were real.

There's a reason why diagnostic tests are run by dedicated personnel who have to demonstrate proficiency and document their methods and results thoroughly. It's not to maintain full employment of lab techs, but to ensure reliability.

But his larger point is very real: the benefit of rapid diagnostic tests is pretty much lost when it takes half a day to get the specimen to the lab, and another half day to report the results. Real-world turnaround times for 2 hour PCR tests are typically 12-18 hours, pretty much destroying their usefulness.

The solution to this lag is not to put a GeneXpert on every floor and let MDs play with them. It's to stop treating microbiology labs like the red-headed stepchildren of the hospital family. Few microbiology tests are reimburseable; the hospital has to pay for them, and thus administrators see micro labs as cost centers to be squeezed, or better, eliminated.

The results are predictable - half of all S. aureus bacteremia patients are on the wrong antibiotic, because MDs are forced to guess at the appropriate treatment absent timely lab results. As more bugs become resistant to more antibiotics, this situation will only get worse.

The rapid (technically, accelerated) MRSA/MSSA test that my team developed at MicroPhage was a commercial failure. This was largely because there was no constituency in hospitals to pay for faster susceptibility results. The healthcare system as a whole would have saved substantial amounts of money as a result of fewer hospital and ICU days incurred by appropriately treated patients. But additional testing means additional lab costs, and few lab managers were interested.

The economic incentives to develop rapid tests are still all wrong. Until that gets fixed, patients will still suffer and die from inadequate treatment, no matter how many doctors we let play lab tech.

 

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And I'm back...

I've been neglecting this blog in favor of business, family and otherwise, but mostly to enjoy the Colorado summer before it is gone.

One of the trips I took was to Trapper's Lake, one of the largest in the state, and also one of the most remote and scenic. At least it was scenic in Aug of 2002, the last time I was there. 2002 was one of the first big drought and wildfire summers in our new climate regime. Several nasty fires had sprung up already, and the sky in Boulder was relentlessly scorched and smoky all summer.

We were hoping to find some relief in the high country, and planned a family backpack trip looping south from Trappers into the Flattops Wilderness, a rolling plateau of lakes, forests and meadows. At 11,000 feet, we figured it would be high enough to be cool and lush despite the drought.

Unfortunately a fire had sprung up near Big Fish Lake, a valley just a few miles west of where we planned to hike. However, a call to the district ranger reassured us that recent cooler weather had calmed the fire down to the point where it was not a concern, and we proceeded as planned.

The hike was everything we had hoped for - cool temperatures, green forests and meadows, and limitless views from the plateau:

By our third day out, however, we began worrying about the smoke on the horizon, and thought it best to start heading back to the trailhead:

We camped at Parvin Lake, and the next morning it was clear that the fire had blown up. Worse, there is only one road out from Trappers, and the fire was heading toward it, possibly cutting us off.

When we got down on the valley floor by the lake, smoke from the fire was rolling over the ridge, turning the sky a dark, evil-looking red. Even more disquieting was the low rumble of the fire - it had become a monster that was rolling through the forest.

We split up at the lake, my wife and daughters taking the short route to the lodge around the east side. I took the longer trail along the west side where our car was parked. Short cutting the trail through a boggy area, I came upon a middle aged woman and her elderly mother, lost, terrified, and heading the wrong way. I walked them (all too slowly) back to the trailhead, jumped in the car and hightailed it down to the lodge. There I found a ranger screaming at my wife to "Get in the truck, now!" and leave with him before the road out was cut off. We wasted no further time with him and started driving as fast as we could down the rough dirt road.

We rounded the ridge and saw flames shooting hundreds of feet in the air, as if the atmosphere itself was on fire. The trees were dwarfed by the size of the flames, which had become a red mountain piled on top of the green mountains. I took a very quick picture:

The trip this year was quite a bit less exciting. And although the frosts are mostly gone - they will take decades to regrow - Trappers Lake is still a place of tranquility and beauty

 

 

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