The Post-Antibiotic Age

Megan McArdle has a rather grim post about bacterial antibiotic resistance:

The superbugs have not only gotten bad fast–from “not really an issue” in 1980 to a major problem today–but they seem to be getting badder faster, as they merrily borrow resistance-conferring genes from each other. Researchers now say they’re seeing resistance show up in the lab, before they even put the stuff into people.

Of course, the most worrying thing is not the effect on the budget. It’s the effect on the people. A world without antibiotics is a world of vast suffering and early death.

Unfortunately, there is no easy solution to this problem and a consideration of the history of antibiotics and methicillin-resistant Staphylococcus aureus (MRSA) may explain why.

The penicillin antibiotics have been known for more than a century but didn’t come into widespread use until 70 years ago. Their effectivceness in treating staph rendered them invaluable during World War II. 2.3 million doses were produced for the invasion of Normandy in 1944. After the war it made its way into widespread civilian use.

The first known case of MRSA was identified in 1961 in the UK. There is epidemiological reason to believe that it originated in the UK and its eradication there has proved elusive. It took 20 years for MRSA to spread from the UK to the USA to any great degree. Since its emergence the incidence in the US has grown to 31.8 cases per 100,000 and about 20% of those are fatal. See here for the rise in MRSA cases among hospital patients.

I would suggest that the emergence and spread of resistant variants of bacteria can be traced to the following causes:

  1. Widespread availability of relatively inexpensive antibiotics.
  2. Abuse of antibiotics. I speculate that the urge to overtreat may be a contributing factor.
  3. Increased travel. Without travel resistant varieties would just stay where they originated.

Now consider the antibiotic linezolid:

When linezolid (Zyvox) received federal approval in early 2000, it was the first completely new antibiotic compound to reach the pharmaceutical market in 35 years. The synthetic compound even proved effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) bacteria, for which no other line of defense existed. Its creator, New Jersey-based Pharmacia, sounded confident that few people would become resistant to the drug. It was not to be. Within months, patients infected with MRSA and VRE were not responding to linezolid.1,2

Such quick resistance epitomizes the dilemma of antibiotics development: Drugs cost hundreds of millions of dollars and take at least a decade to develop, and then become increasingly less effective. (see ‘Renewing the Fight Against Bacteria,’).

In the past, a classic screening approach, which tests in vitro the inhibitory effect of synthetic and natural compounds or extracts, led to the discovery of many current antibacterial drugs. Linezolid, for example, was developed in this way: thousands of compounds were reviewed to find one that kills bacteria. Today, this method yields few, novel, promising structures. The related method of developing second and third generation drugs based on existing pharmaceuticals is no longer considered an option because cross resistance reduces the effectiveness of macrolides (based on erythromycin), rifapentine (based on penicillin), and carbapenems (based on imipenim).

In many places in the world antibiotics are available over the counter and here in United States incentives to do more, effective or not, lead to over-prescription. It has been suggested that the routine use of antibiotics in animal feed contributes to the development of resistant bacterial strains as well.

Modern travel, the wide availability of antibiotics, and misuse both of patients and physicians create an evnironment in which the development of resistant strains of bacteria is inevitable and once established, these strains have proved very difficult to uproot. The increasing cost (even in the absence of regulatory barriers, a frequent target) makes it unlikely that the development of new antibiotics will keep up with the evolution of new resistant bacterial strains.

Barring some development to fight bacteria other than the development of new antibiotics we may well be entering a post-antibiotic age. I don’t look forward to this eventuality. Antibiotics have been very good to my family—without them I probably wouldn’t be here. In the 1880s nearly every adult male in my lineage died from bacterial disease (tuberculosis, staph). Puerperal fever (septicemia following childbirth) was a common cause of death among my female ancestors. As late as 1930 people in my family were dying of tuberculosis but since 1940 nobody in my family has died of bacterial disease. We may be returning to those days.

22 comments… add one
  • john personna

    I’ve only been following this casually, but isn’t agricultural reform relatively easy? I mean, in a technical sense. Whether the farm lobby could be brought to accounts is another question.

    New superbug that is spread by farm animals: Doctors raise concern over worrying resistance to antibiotics

  • And, returning to a favorite topic of yours, Denmark, the Danes have demonstrated that eliminating routine use of antibiotics in animal feed is practical.

    While it’s practical, as you suggest there may be a political problem. I think education is part of the answer but, unfortunately, people frequently operate by fads and conservatism (not in the political sense but in the sense of holding on to old beliefs) and farmers are no exception.

  • john personna


  • PD Shaw

    Denmark banned non-theraputic use of antiobiotics, but ended up increasing the use of theraputic antiobiotics in livestock. Industry says the ban caused the increase. The other side says there are new strains of bacterial infection that are responsible. The link between animal and human strains is also disputed (From jp’s link: “The source of these infections is unclear, but it is thought only a small proportion – less than one per cent – is linked to food.”)

  • PD:

    As you may have noticed from my very tentative mention of the use of antibiotics in animal feed as a possible cause of the development of antibiotic-resistant strains, I think the more important issues have to do with patient and physician abuse of antibiotics.

  • john personna

    Seems an odd objection, PD.

    “Non-theraputic use” means using medicine as a food suppliment.

    “theraputic use” means as treatment, in response to illness.

    Of course reduction in wholesale use would increase the targeted use. That’s exactly what you want. (I don’t think you’ve found evidence that total dosage per animal went up!)

  • john personna

    Dave, I definitely agree that physicians have over-prescribed … but you know, we never went retail, and had people popping antibiotics every morning with their vitamins.

  • but you know, we never went retail, and had people popping antibiotics every morning with their vitamins.

    No, but many places in the world did and travel is pretty free. In Mexico, for example, antibiotics were available over the counter without a doctor’s prescription until last year and compliance still isn’t great.

  • john personna

    Yes, I know. The wikipedia causessection is a pretty good summary.

  • PD Shaw

    There have been some studies showing overprescrition of antibiotics for viral infections. The suggestion being that doctors too often will prescribe them when a tired, cranky parent wants the doctor to do something about their crying infant. As I recall we were given a flyer explaining what antibiotics are good for and what they are not either at the hospital or the first doctor’s appointment.

  • PD Shaw

    jp, I’m not really objecting. If the science showed that use of the antibiotics for that purpose was unsafe, the FDA would be required to withraw approval of that use.

    Until then, it is a political issue, whether or not to ban the use of the drugs based upon a precautionary principle or an evaluation of the trade-offs.

  • steve

    Withdraw licensing for practitioners, and this gets worse. Stopping overuse will require regulation. Physicians will tend to maximize return by giving the customer what they want, ie, the antibiotic.


  • john personna

    PD, here’s a good couple line from the wikipedia page:

    “In 2000 the US Food and Drug Administration (FDA) announced their intention to revoke approval of fluoroquinolone use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone resistant campylobacter infections in humans. The final decision to ban fluoroquinolones from use in poultry production was not made until five years later because of challenges from the food animal and pharmaceutical industries.[29] T”

  • steve

    Oops. Interesting article about Netherlands and medicine.


  • PD Shaw

    jp, I’m not sure that Wiki entry get’s the context: the FDA approved the use of these antiobiotics for these uses. In order for FDA to withdraw its approval for those uses (or citizens petitioning the FDA to do so), the FDA must prove the use is not safe based upon scientific method in a hearing with an opportunity for the other side to present and challenge any evidence. It took five years to prove one antibiotic unsafe; there is a lawsuit regarding two other antibiotics that was filed earlier this year. I read it a few months ago, and NRDC seems to be claiming that the FDA can’t prove the use is safe, which looks like burden shifting.

    It certainly feels like it’s difficult to prove safety or unsafety at this time, which means gridlock for most of the antibiotics.

  • john personna
  • john personna

    BTW, I like your optimism (blithe or not) PD, that industry would only want to prove the science, and never argue from mere commerce.

  • sam

    Well, if we just abolished the FDA, all this stuff would be taken care of by the market…

  • Well, if we just abolished the FDA, all this stuff would be taken care of by the market…

    Oh absolutely.

    Just when I thought you were worth taking seriously sam you have to post this kind of utopian nonsense.

    Or here lets try this,

    If only we just moved over to the liberal socialist ideal government would take care of all this stuff….

    Somebody should start a blog called “The Straw Man” and post all these kinds of insipid arguments so we have a handy reference.

  • sam

    Jesus, Verdon, smog got to your humor center?

  • Brett

    If it’s any consolation, I remember reading somewhere that the heavily cross-resistant strains tend to die out when you more heavily constrain the use of anti-biotics. That type of cross-resistance has costs for the bacteria that have then, which is why vulnerable bacteria usually out-reproduce them.

  • Danelle

    If you want to really understand the complexities and implications of the subject seek out materials written by Paul Ewald. A May 99 article in the Atlantic is a good place to begin. See:

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