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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