This article originally appeared at Forbes and has been republished here with permission of the author.
It was not until the years just after World War II when streptomycin, the first truly broad-spectrum antibacterial agent, came onto the market, and penicillin began to be widely available that the Golden Age of antibiotic therapy really began. Before that, even seemingly trivial infections of the skin, lungs or other organs could lead to sepsis and death. In the 1920’s, for example, my maternal grandmother died at age 30 from an infection contracted after a routine gall-bladder operation.
We may now be on the verge of returning to that pre-antibiotic era, a prospect that terrifies public health experts.
Bacteria are champions of Darwinian selection–as we try to kill them with antibiotics, they mutate in myriad ways in order to survive. And they have quite a repertoire: Among other tricks, they develop less permeable walls to keep the antibiotics out, create ways to degrade or extrude them or alter the intracellular targets so that the antibiotics no longer work on them. Bacteria can even transfer these evolutionary adaptations from one species to another, making it ever more imperative for us to come up with new antibiotics that work through novel mechanisms. It’s a never-ending escalating arms race, and the harsh reality is that the bacteria are winning it.
Increasingly, microorganisms are developing resistance not only to single antimicrobial agents, but to several. These latter organisms are called multidrug-resistant, or MDR, strains. In some cases, the microorganisms have become so resistant that no available antibiotics are effective against them.
When it comes to the development of innovative new antibiotics, the future looks grim. It’s been more than 30 years since a fundamentally new type of antibiotic was discovered. Whereas fields like cancer therapy and diabetes have hundreds of potential treatments in the pipeline, only 37 antibiotics are currently in clinical development, few of which have the potential to fight emerging pathogens. At the same time, rapidly emerging drug-resistant bacteria are quickly bringing the specter of a “post-antibiotic” world closer to reality.
Already, doctors are seeing patients with resistant infections that respond to few or no existing treatment options. A particularly frightening development was the discovery earlier this year of a gene called mcr-1 for the first time in bacteria in a human in this country. It has subsequently been found in three other American patients and in two intestinal samples from pigs tested by the U.S. Department of Agriculture. This is of particular concern because according to the CDC, “the gene makes bacteria resistant to the antibiotic colistin, which is used as a last-resort drug to treat patients with multi-drug-resistant infections,” and it “exists on a plasmid, a small piece of DNA that is capable of moving from one bacterium to another, spreading antibiotic resistance among bacterial species.”
This situation will only get worse without innovation to bring to market new drugs for highly resistant infections.
There is legislation awaiting passage by the Senate that could begin to afford better protection to Americans from the growing threat of antibiotic resistance, which claims 23,000 lives in the U.S. a year and accounts for millions of infections. Key provisions in the 21st Century Cures Act, which passed the House this week, take aim at antibiotic resistance. They would spur urgently needed innovation of new antibiotics, preserve the effectiveness of existing ones, and improve surveillance of resistant bacteria.
Among the provisions of the 21st Century Cures Act aimed at combating antibiotic-resistant bacteria is a policy that would establish a limited-population antibacterial drug (LPAD) pathway at the Food and Drug Administration to help advance the development of such urgently needed drugs. It would enable the FDA to review and approve new antibiotics specifically for high-risk patients with serious and life-threatening bacterial infections resistant to available treatments. Drugs’ safety and effectiveness would be studied in substantially smaller, more rapidly conducted and less expensive clinical trials—much like FDA permits for other rare diseases. These provisions are critical to making drug development feasible because the pool of patients with serious and life-threatening bacterial infections who would be eligible for clinical trials is not yet large.
After FDA marketing approval, LPAD products would be narrowly indicated for use in small, well-defined populations of patients, and the LPAD pathway incorporates important safeguards to help ensure these drugs are used appropriately. These include prominent branding, to clearly indicate that the antibiotic was approved based on the unique needs of a limited population of patients, FDA review of marketing materials and post-market monitoring of how LPAD drugs are being used.
LPAD is a bipartisan, thoroughly-vetted, common sense policy that has broad support from a diverse group of stakeholders, ranging from pharmaceutical companies and venture capitalists to public health organizations and scientific leaders.
Whether as part of the 21st Century Cures Act or as a standalone bill, it is critical for Congress to pass LPAD legislation as soon as possible. It would provide a desperately needed boost to antibiotic innovation and make a life-saving difference for some of the sickest patients. We can’t afford to wait any longer for public policy initiatives to stave off the extinction of the antibiotic era.
Henry I. Miller, a physician, is the Robert Wesson Fellow in Scientific Philosophy & Public Policy at Stanford University’s Hoover Institution. He was the founding director of the FDA’s Office of Biotechnology. Follow him on Twitter @henryimiller.
