More on looking the part

Mike Edmonds has a few comments regarding the study on lab coats and cleanliness from Dr. Silvia Munoz-Price and colleagues.  Lab coats are washed about every 12 days on average, even though 90% of the respondents were aware that they were potentially contaminated.  The most prevalent reason given for wearing lab coats? (hint, it is not to do lab work) - Instead, it is "to symbolize their profession", a reason that must be immensely gratifying to some.  

Broad-spectrum badness

Here is another report describing high rates of inappropriate antibiotic use, this time in outpatient dialysis centers. Fully 30% of the antibiotic prescriptions written were inappropriate, usually because criteria for infection were not met, or because a broad-spectrum antibiotic was used when a narrow-spectrum antibiotic was the better choice.

In an earlier post I made the point that developing broad-spectrum antibiotics is not necessarily a good thing. The rationale here is that such antibiotics, while providing some therapeutic benefit, are usually not optimal. Narrow-spectrum antibiotics are preferred when the identity and antibiotic susceptibilities of the infecting bug are known, from the standpoint both of patient benefit and antimicrobial stewardship.

Broad-spectrum antibiotics thus enable second-best prescribing practices - they allow doctors to treat patients without ordering a microbiology report, or allow them to fail to follow up on the report. Broad-spectrum antibiotics such as vancomycin are valuable medicines - but is apparent that they also can be used as a crutch to support inferior medical practices.

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The end of the golden age

I should explain what I mean by "The End of the Antibiotic Era". It's not that antibiotics will cease to be used or to be useful. Or that new antibiotics won't be discovered. Instead, I'm defining the antibiotic era as the period in which the average well-trained doctor could prescribe antibiotics on the basis of clinical signs and symptoms alone, and be highly confident that they would work. This era started in the 1940s with the introduction of sulfonamides and penicillin, and (I would say) ended in the 2000s when methicillin resistance in S. aureus became widespread.

The impact of antibiotics was profound and is certainly comparable to any other technological advance of the period. Only the introduction of clean water and food has clearly had a greater impact on human health, although an argument could also be made for vaccination. Death rates dropped from 250 per 100,000 Americans in 1937 (the beginning of the golden age of antibiotics) to about 50 by 1953. The effect on infant mortality was even more dramatic, dropping from 5500 per 100,000 live births in the late 1930s to half that by the mid-1950s. Even if only half of this drop is attributable to antibiotic use, that works out to more than 120,000 lives saved per year.

Of course, resistance emerged soon after antibiotic use became common. But pharmaceutical companies became very good at identifying lead compounds (usually from soil microorganisms) and then chemically modifying them to enhance uptake, reduce toxicity and thwart resistance mechanisms. Aminoglycosides, macrolides, tetracyclines, quinolones and cephalosporins were introduced and then improved on, generation by generation. Not only were these medicines highly effective, they became remarkably cheap. The cost of a life-saving course of antibiotics was (and usually still is) less than that of a dinner at a nice restaurant.

Because these drugs were also very safe and nontoxic, they were used as placebos and prophylactics. I can well remember our whole family lining up for penicillin injections in the 1960s when we reported to the doctors office with colds. I'm sure he knew that we did not have bacterial infections, but saw little downside: we went away happy, he made a few extra bucks, and could rationalize that he was practicing preventive medicine. In the current era, anyone who practices this sort of Dr. Feelgood approach to antibiotic administration should be considered a public nuisance and threat to public health, and be dealt with accordingly.

As we leave the golden age of antibiotic effectiveness, there are several changes that we can expect to see:

• More people will sicken and die from bacterial infections. This is already happening of course. I don't expect mortality rates to return to pre-antibiotic levels because of better public health infrastructure and supportive care, and because new antibiotics will be introduced. But nearly everyone will know someone, or be someone, who has suffered from a serious infection that could not readily be resolved due to resistance.
• Because of this suffering, antibiotic effectiveness will come to be viewed as a public resource, or commons. Abusing antibiotics is no less a tragedy of the commons than fouling the water or air - shotgun prescribing may provide an immediate benefit to a sick individual, but it will end up making many more people sick.
• Doctors will not be able to resolve this tragedy on their own. Most are aware that prescribing antibiotics empirically (ie., in the absence of any test results that indicate the appropriate drug to prescribe) contributes to the problem of increased resistance. But faced with a seriously ill patient, it is too much to ask of doctors that they withhold a treatment that might work, due to theoretical concerns that someone else, somewhere down the line, is somewhat more likely to get an untreatable infection.
• Therefore antibiotic use will become much more regulated. Your GP, upon seeing a spot in your chest X-ray, cannot start treating you with cisplatin or any other powerful cytotoxic therapy. Similarly, the use of whole classes of antibiotics will increasingly be restricted to specialists, often with the involvement of hospital pharmacists.
• As a result, the cost of antibiotic therapy will rise significantly. On the whole, this will be a good thing. Antibiotics will be used more discriminately, and profit margins will increase, incentivizing new discovery R & D. So long as these costs are equitably distributed, public welfare will be increased.
• A market for diagnostics that can rapidly determine antibiotic resistance and susceptibility will be created, in order that antibiotics can be still prescribed in a timely way, but based on evidence. Several accelerated tests, including one from my former employer (MicroPhage, Inc), have been introduced. None has gained much traction - hospitals don't yet see appropriate antibiotic use as a sufficiently compelling problem to warrant the extra costs of testing, which they usually cannot bill to insurers. This will change.

In short, the end of the golden age of antibiotics will not mean the collapse of civilization - climate disruption or new virus emergence are much more likely candidates for that role. But people will die, changes will have to be made, and we'll all wish we had made them much sooner.

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Looking the part

Wow. Stephanie Dancer has written an editorial for the British Medical Journal lashing out at the apparent plague of doctors who, by not wearing neckties, "...intimate a lack of personal hygiene and correspondingly lower standards of hygienic behaviour". She wants all such "scruffiness" to stop immediately, because lack of a tie could "indicate something more sinister".

Several studies (like this and this) have found that neckties carry pathogens, which is hardly surprising as they are a) handled by ungloved hands, b) apt to brush up against contaminated surfaces and c) rarely laundered.

Mike Edmond has disposed of the more incoherent of Dancer's objections and arguments. But it's pretty clear from the spluttering tone of the editorial that it is really all about maintaining status because "Doctors are members of a distinguished profession and should dress accordingly". I suspect that her notion of an ideal patient-doctor relationship would look a bit like this:

No one has ever proved that a patient was infected by a contaminated necktie (or long-sleeve shirt, or lab coat), but ... really? I would think that knowing you are carrying around a contaminated item of clothing would be all the evidence that's needed to make a change. Unless of course your first priority is to look like a TV doctor.

 

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The origins of second-best medicine

Medicine is not a science, but an art empowered by science. So it is little surprise to find that the same social factors that shape other workplaces - habit, hierarchy and deference to colleagues personal sensitivities - shape the antibiotic prescribing practices of physicians. Who likes to stand up and tell an esteemed colleague that they are making a mistake?  Well, some people do, but they soon get labeled as habitual contrarians to be ignored or suppressed. Not a career path for success. 

Esmita Charani and colleagues at The National Centre for Infection Prevention and Management in London have put a bit of science behind the suspicion that doctors behave in their workplace pretty much like everyone else does in their workplace. In a series of structured interviews with doctors, nurses and pharmacists, they found that evidence-based guidelines and policies counted for much less than personal experience, intuition and personal authority when it came to actual antibiotic prescribing practices. 

How big a problem is this?  After all, doctors care about giving the best care possible, and want to see their patients get better.  If poor prescribing practices were leading to bad outcomes, surely they would stop those practices - right?

The problem is not that doctors don't care, it's that they come equipped with human brains. And human brains are notoriously unreliable when it comes to evaluating success rates. We are good at remembering a few spectacular successes, thinking that they validate our competence. We forget the equally spectacular failures, believing that they are due to an unforeseeable combination of circumstances and bad luck. Most of all we are just plain bad at distinguishing natural fluctuations in success rates from pure chance.  

Baseball offers a great example of this phenomenon. Over the course of a week of baseball games, a star player will typically get 7 or 8 base hits. A journeyman would get 6, and a scrub would get 5. The difference between best and worst is a single event every few days.  No one could possibly tell the difference just by watching. That's why baseball teams keep score -  so that they always put the best players out on the field, rather than trust to recent experience, reputation or intuition. 

For critical diseases, such as Staph aureus bacteremias, the differences in outcomes between the best prescribing practices and the second-best are about the same as the differences between a star player and a scrub. MSSA patients that are prescribed general-purpose broad spectrum antibiotics have  roughly a 25% chance of dying; those whose prescriptions are evidence-based, and are specifically targeted have their risk of death reduced by half.

An individual doctor, who might see only 25 or fewer MSSA bacteremia cases per year, is not likely to notice the extra death or two that results from suboptimal prescribing practices. No doubt that patient was weaker to bnegin with, and had other complications. Nor will they be aware that the survivors spent more time in the ICU and more time in the hospital than necessary: they have treated their patients with a therapy that was helpful and most have survived. Why question what seems to be working?

Individual human brains are basically incapable of getting this right; we can't distinguish best from second best outcomes that are separated by frequencies of 10 or 20%. We need well designed and well controlled studies to identify these differences, and then we need to pay attention to them. But this can't happen if we defer to authority, trust intuition over published best practices, or remain quiet for fear of treading on a colleague's turf. 

About 5000 people are killed by MSSA infections each year in the US, and it is likely that the majority received suboptimal antibiotics. So it is safe to say that the behavior described by Charani et al are responsible for up to a thousand excess deaths per - for just one bad bug. That seems a pretty high price to pay to manage doctor's egos.