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When your child has a bacterial infection, you take her to the doctor, get a prescription for an antibiotic, and, in most cases, all is soon well.
But while antibiotics work for most patients with a bacterial infection, they may not for all infections. Public health agencies around the world are dealing with the growing challenge of bacterial resistance to antibiotics, which can make these medications ineffective.
The Centers for Disease Control and Prevention (CDC) reports that every year at least 2 million illnesses and 23,000 deaths in the United States are caused by antibiotic-resistant bacteria. The problem is especially serious for patients who have few viable antibiotic options; this can occur with certain types of serious bloodstream infections and with gonorrhea infections, among others.
Overuse of antibiotics in both humans and animals helps drive the evolution of resistant bacteria. Why? The bacteria have a natural tendency to mutate and to acquire genes from other bacteria. These changes can enable them to resist the antibiotics and flourish in environments where antibiotics are used. As the resistance genes move between bacteria, the bacteria themselves spread through soil, water, and wildlife. Over time, with continued antibiotic use, the situation worsens.
Resistance Spreading Globally
Scientists are concerned that resistant strains of bacteria could spread globally through travel or trade, including the exchange of foods. To help identify the presence of antibiotic-resistant bacteria as early as possible, and take steps to control their further spread, the FDA is using cutting-edge technology called whole genome sequencing (WGS).
A genome is an organism’s complete set of genes. In the 20 years since the first bacterial genome was completely sequenced, the science has advanced dramatically. The first bacterial genome sequence was uncovered in 1995 at a cost of several hundred thousand dollars and many months of work. Now it costs around $50 per genome and dozens can be done together overnight.
“For the first time, we can rapidly determine the entire collection of known antibiotic resistance genes in an individual bacterium. This is allowing new insights into the nature and magnitude of the resistance threat,” says Patrick McDermott, Ph.D., director of FDA’s National Antimicrobial Resistance Monitoring System (NARMS).
“And, because the database of resistance genes is growing, due to work by scientists around the globe, we can see what others are finding and quickly ascertain if resistance threats emerging in other countries also are present in the United States.”
Whole genome sequencing is also revealing new types of resistance genes in disease-causing bacteria, says McDermott. For example, NARMS data showed a rapid rise in gentamicin resistance in the foodborne bacteria, Campylobacter. Gentamicin is an antibiotic used to treat certain serious bacterial infections. WGS analysis showed that the genes causing this resistance are numerous, and most had never been seen before.
Controlling the Problem
Surveillance plays a big part in identifying the problem and possible solutions. “You need a monitoring system in place to understand how big the problem of antibiotic resistance is—and whether the situation is improving or getting worse,” McDermott says.
To that end, NARMS was established in 1996 as a partnership of state and local public health departments, the FDA, the CDC, and the U.S. Department of Agriculture (USDA). NARMS tests foodborne bacteria from retail meats, food animals, and clinical cases of human illness to see which resistant bacteria are moving through the food supply and to what extent.
Surveillance data can be combined with other public health data to reveal useful information about how resistant infections differ from susceptible infections (infections antibiotics effectively combat). These data are also important to determine how successful the interventions designed to limit the spread of resistance actually are. “The ultimate goal is to preserve the effectiveness of antibiotics for use in both humans and animals,” says McDermott.
Detecting Antibiotic Resistance Genes
WGS has been an important tool in the continuing investigation into the presence in the United States of a gene (mcr-1) that causes resistance to the drug colistin. Colistin is considered a drug of last resort to treat some serious infections.
This gene was first discovered by scientists in China in November 2015, and was later detected in Europe, Canada and elsewhere. In response, NARMS teams looked at the DNA sequence of genes for more than 100,000 individual bacteria in the national database, which includes information from NARMS, FDA’s GenomeTrakr National Foodborne Pathogen database, and other sequence data housed at the National Center for Biotechnology Information, part of the National Institutes of Health.
“Within a matter of hours, it was now possible to determine that this new resistance gene was not present in any of these thousands of isolates,” says McDermott. “We didn’t have to go back to the laboratory to perform new experiments. We could just look at the DNA data.” Later studies were conducted by NARMS scientists using selective enrichment of animal samples (i.e, samples were exposed to colistin to selectively kill anything bacterial that wasn’t resistant) and found two instances of mcr-1 in swine from the U.S. out of 2,000 samples examined.
The difficulty in finding resistant organisms, coupled with the fact that the drug is not used in food animals in the U.S., suggest that colistin resistance poses a low risk to public health in this country. Thus far, the mcr-1 gene has been identified in four people in the U.S. treated for E.coli infections. NARMS will continue to monitor for the mcr-1 gene to watch for any changes in the situation.
FDA’s efforts do not stop at its borders. “Antibiotic resistance is an international challenge,” McDermott adds. “We are committed to sharing U.S data with other countries. This transparency and partnership is indispensable to combating antibiotic resistance globally.”