More than 2 million Americans each year become infected with a microbe resistant to one or more of the first-line antibiotics designed to treat that infection. These antibiotic-resistant infections are both costly and deadly, according to the U.S. Centers for Disease Control.
They are associated with hospital stays and worse outcomes, including at least 23,000 deaths per year in our country alone. The annual economic impact of antibiotic resistance in the United States is estimated to exceed $20 billion in excess health-care costs and an additional $35 billion in lost productivity. Infections acquired in hospitals pose a risk to patients in intensive-care units and surgical wards, and they are particularly grave among vulnerable populations, such as the elderly, those receiving cancer chemotherapy, patients with kidney failure or rheumatoid arthritis, and newborn infants.
Most of us are familiar with methicillin-resistant Staphylococcus aureus, or MRSA, the “superbug” that has spread beyond hospitals and into communities, producing serious outbreaks in prisons, barracks, schools and athletic facilities. But other threats are emerging. Carbapenem-resistant Enterobacteriaceae, or CRE, which includes E. coli and related strains, are resistant to all — or nearly all — existing antibiotics. Half of patients with CRE bloodstream infection have died. Antibiotic resistance is spreading, too, among strains of tuberculosis and the malaria parasite, causing untold misery in regions of the world with the fewest resources to fight back.
Dr. Margaret Chan, director-general of the World Health Organization, warns that we risk entering “a post-antibiotic era ... in effect, an end to modern medicine as we know it.”
What drives antibiotic resistance? At one level, it’s simple Darwinism. When a life-or-death selection pressure is placed upon the bacterium, mutations that favor survival create the stepwise evolution of resistant strains.
But human behaviors leading to inappropriate overuse of antibiotics are equally responsible. Doctors too often prescribe — and patients too often seek out — antibiotics for self-limited viral infections “just to be safe.” Or physicians administer unnecessarily broad-spectrum antibiotic regimens that disrupt the precious balance of healthy “good citizen” bacteria residing on and inside our bodies.
Antibiotic resistance is further fueled by widespread use of antibiotics to promote growth of agricultural livestock — which now accounts for as much as 80 percent of the total antibiotic use in the United States. The ongoing outbreak of several hundred salmonella infections linked to California chicken farms has been especially devastating because these strains were already antibiotic-resistant; more than 40 percent of the people who have been sickened have required hospitalization.
These practices must change. With public support, policymakers, drug manufacturers and microbiology researchers must rise together to meet this historic challenge.
For decades, the pharmaceutical industry has shied away from antibiotic development in favor of more lucrative chronic disease targets, such as heart disease, diabetes and high blood pressure. The development pipeline of new antibiotics is dangerously dry. Possible solutions include new public-private partnerships to share the costs of the necessary clinical trials or incentivizing changes in the length of patent exclusivity or premium drug pricing.
Scientifically, we need to rethink and expand our approach to new anti-infective therapies. Modern cancer therapy has been revolutionized by the development of drugs specifically designed to target mutant proteins in malignant cells. So, too, we must develop antibiotics highly specific for the infecting pathogen, drugs that spare the healthy microbes of our gut and limit the continual selection pressure for antibiotic resistance.
One such strategy involves defining the “virulence factors” of the disease-causing bacteria — those toxins and molecules that harm our body and resist clearance by our immune system. New drugs designed to block these factors could disarm the individual pathogen, allowing the body to eliminate it. We should explore new medicines that boost the natural antibacterial functions of our white blood cells and work in concert with antibiotics to clear difficult infections. We should seek new classes of antibiotics from unexplored frontiers, such as the deep oceans or the human microbiome.
We have dug ourselves a deep hole, and these pathogens are perilously close to burying us. Fortunately, there is every opportunity for San Diego, with its world-class universities and academic medical centers, renowned private research institutes, and large cluster of biotechnology and pharmaceutical companies, to stake claim as the innovation leader in addressing this present and ever-increasing threat to our public health.
We must act — and act quickly.