“We talk about a pre-antibiotic era and an antibiotic era,” Tom Frieden, then-director of the U.S. Centers for Disease Control and Prevention (CDC), said during a press briefing in September 2013. “If we’re not careful, we will soon be in a post-antibiotic era.”
Within hours of the briefing, media articles about Frieden’s remarks and the landmark CDC report that assessed the state of antibiotic resistance in the U.S. began circulating. Frieden’s warning of a “post-antibiotic era,” proved to be a succinct, provocative way to summarize the possibility of a world in which bacterial infections can no longer be effectively combated.
As much as we would like to consider resistance a modern danger, it did not develop after the so-called “golden age” of antibiotics but rather in tandem with it. One could say that antibiotic resistance is an issue which predates the use of penicillin.
Admittedly that might be a little misleading — but only if you consider penicillin to be synonymous with modern antimicrobials. In reality Alexander Fleming’s famous discovery of penicilin was not the first antibacterial on the market: Sulfonamides were.
Derived from a compound used in the dye industry, sulfa drugs enjoyed widespread popularity throughout the second half of the 1930s and into the early 1940s.
In their prime, sulfa drugs cured the likes of Winston Churchill and President Franklin Roosevelt’s son, but within a few years of their introduction, resistance had become a serious issue.
When penicillin was finally developed for use in humans, its job was partly to cover those diseases against which sulfonamides were no longer effective. Like the sulfa drugs, however, penicillin’s honeymoon would be short.
The first research paper on penicillin resistance was published in 1942, only about a year after the antibiotic was first administered to human patients, and the same year it was first mass-manufactured.
This paper described the case of a man named J.B., a patient in a Massachusetts hospital whose Staphylococcus bone infection failed to resolve, even after extensive treatment with penicillin over the course of three weeks.
By 1949, less than a decade after the paper appeared, almost 60 percent of Staphylococcus strains were penicillin resistant.
Fleming was one of those who recognized this expanding threat of antibiotic resistance. He closed his 1945 Nobel Lecture with a warning, summarized by a scenario in which a husband fails to complete his course of antibiotics, infects his wife with the resulting drug-resistant bacteria and causes her death.
When Fleming issued his caution, he was concerned with acquired resistance through vertical gene transfer or spontaneous genetic mutations, which improve a bacteria’s resistance and can be passed on to offspring.
In 1951, however, there was the first description of horizontal gene transfer. This mechanism involves the transfer of DNA and resistance genes between organisms of the same or different species.
Over the next half-century, resistance developed in alongside antibiotic breakthroughs. Tetracycline was approved by the FDA in 1952 and resistance was reported in the same year. Meticillin was approved in 1960, with resistance reported the following year.
Multiple-drug resistance also became an issue. By 1960, for instance, almost one-tenth of Shigella strains isolated in Japan were resistant to streptomycin, tetracycline and chloramphenicol.
This does not mean there is anything wrong with antibiotics. They have saved millions of lives, slashed death rates and stretched life expectancies. The very reason why resistance is such a problem is because a world without antibiotics would be an unimaginable one.
Those afflicted with common infections, women in childbirth, children with skin injuries, transplant recipients and others would once again face unprecedented levels of risk.
If we want to find a sustainable way to make infectious diseases obsolete, antibiotics are not the answer and never have been. In fact, researchers have discovered genes in bacteria frozen for centuries or isolated in caves, genes which would grant bacteria resistance to some of our modern antibiotics.
This suggests that resistance genes are not a result of new therapies; the therapies simply made resistance genes more advantageous.
So while measures such as eliminating the prescription of inappropriate antibiotics and discovering new antimicrobials are necessary, even if implemented perfectly, they are only stopgaps.
Instead resources should be focused on preventing infections and developing ways to fight infections that do not increase selective pressure, such as regulating host responses.
Although easier said than done, it is likely that the next breakthrough for fighting bacterial infections will not come in the form of an antimicrobial but as an entirely new concept as revolutionary to us as antibiotics were to the world 100 years ago.