Antibiotic resistance: Can the clock be turned back?
In late May, the Centers for Disease Control and Prevention (CDC) revealed a Pennsylvania woman had been infected with strain of E. coli bacteria resistant to the antibiotic of last resort. While the woman’s infection did respond to other antibiotics, the news underscored the growing threat of deadly pandrug-resistant “superbugs." At the time, CDC Director Tom Frieden warned of the risk of living in a “post-antibiotic world.”
Since the discovery of penicillin in the 1940s, antibiotics have greatly reduced illness from infectious disease and saved countless lives, but widespread and often indiscriminate use has left many ineffective as the bacteria they were designed to fight adapted. They have also been widely used in agriculture to increase livestock growth and in soaps and other types of cleansers. Around the time of the CDC announcement, the Department of Agriculture also reported finding the same colistin-resistant E. coli strain in an intestine sample from pig that had been raised in Texas.
According to the CDC, at least 2 million people a year in the U.S. are infected with antibiotic-resistant bacteria, and at least 23,000 die from those infections.
While not new, efforts to curb the use of antibiotics and slow the rise of resistant organisms are taking on new urgency. A House oversight subcommittee held a hearing on Tuesday to discuss the risks associated with superbugs and the country’s preparedness to deal with superbug outbreaks. The Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria is holding a public meeting June 21-22 on incentives for the development of new vaccines, diagnostics and therapeutics, as well as the Food and Drug Administration’s recent guidelines on antibiotic use in food-producing animals.
“When you think about antibiotic resistance, there are a limited number of things that we can do on our end to address the problem,” says Arjun Srinivasan, associate director for healthcare-associated infection prevention programs at the CDC. “We can’t control how fast bacteria are going to mutate, so we have to control things that are within our power."
One of those things is to try and slow the selection of highly resistant bacteria by reducing antibiotic use, Srinivasan says. “That means ensuring that antibiotics are used only when they are needed, and that whenever they are needed, we’re always giving the right antibiotic at the right time for the right duration.”
For years, doctors took a “better safe than sorry” approach to antibiotics, prescribing them whenever people presented with symptoms that might suggest a bacterial infection, especially if identifying the infectious organism required a lengthy culture test. “A lot physicians in the last 30 years or so have been taught to use antibiotics in a way that is more of an insurance,” says Michael Keegan, who leads the Antibiotic Stewardship Program at Pershing Yaokley & Associates (PYA). That strategy has proven costly, however, and the focus increasingly is on identifying the organism before establishing a course of treatment.
Better diagnostics can help reduce overutilization
With the growing availability of polymerase chain reaction testing, doctors can now test specifically for generic material in viruses and bacteria and know within hours if a patient requires an antibiotic and which antibiotic they should get. Being able to provide that information very quickly can allow doctors to target the antibiotic for the particular organism and see a better outcome for their patient, says Dennis Grimaud, CEO of infectious disease identification firm Diatherix. It can also reduce the use of drug “cocktails,” another source of overutilization.
Huntsville, AL-based Diatherix’s platform can simultaneously identify up to 26 viral and bacterial pathogens, Grimaud says. The firm works with physicians to develop panels that are specific for certain conditions — e.g., pneumonia or a wound. The company also brings in key opinion leaders educate clinicians on the latest development in the infectious disease industry.
But genotypic testing is still not the norm, says Grimaud, who sees it as complementing traditional culture tests. “We’ve all been trained on phenotypic expression; genotypic expression hasn’t been that accepted yet.” Yet if you look at infections like whooping cough or Legionnaire’s disease, where the organisms are difficult to grow and results are needed quickly, genotypic expression is really what is needed, he posits.
Another thing holding back PCR tests is the cost. While Medicare and Medicaid do cover for PCR, they’re still expensive and need to be used in a discriminating fashion, says Keegan.
The conundrum, says Srinivasan, is what if the diagnostic test costs more than the antibiotic. “We need the payers at the table to make sure that we have the right strategies moving forward to help us understand that, yes, though the short-term cost of the diagnostic might be more expensive than the antibiotic, the long-term cost of using the antibiotic without the diagnostic might be very, very high.”
Updating clinical practice guidelines to align them with what is known about drug resistance is also needed, experts say. Hospitals currently are instructed to put patients on an antibiotic within two hours of admission, after presenting with an infection, or face being penalized. But how long should they stay on that drug before changing the treatment regimen? “If you use culture, it could be three days, and you could be staying on the wrong antibiotic for that three-day period,” says Grimaud.
Many of today’s guidelines about the usefulness of antibiotics also don’t fit with what infectious disease specialists are seeing genotypically for drug resistance, he adds.
Srinivasan agrees. “One of the areas where a lot of practice guidelines have fallen short is in looking at the picture holistically,” he says. “What you see is a list of 'here are all the things that might be effective in treating the infection for this practice guideline.'”
Instead, groups should be looking at practice guidelines through the lens of antibiotic stewardship, identifying which antibiotics might be effective for a condition and which should be first-line, second-line and third-line therapy, Srinivasan says. One group that has done a nice job of that is the American Academy of Pediatrics, he adds.
Antibiotic stewardship is also helping to reduce antibiotic use. For example, Keegan’s group hosted a project in a smaller community in eastern South Dakota, bringing together the public health department, hospital and health clinics, pharmacies, nursing homes, and a mental health center. The focus was on creating a safer environment for patients from a bacterial standpoint, and it “was highly successful because everybody bought in,” he says. Because it was a farming community, physicians were also able to make the connection between antibiotic resistance and animal growth promotion.
Working collaboratively with whole communities and with multiple hospitals within a state, stewardship has helped to drive down costs, prevent infectious complications, decrease antibiotic use and focus attention on the antibiotics that have the highest risk,” Keegan says.
To help curb antibiotic resistance, Congress last year authorized hundreds of millions of dollars to the CDC, FDA, National Institutes of Health and other federal agencies fighting the good fight. More than $150 million went to the CDC to support programs aimed at preventing and monitoring superbug outbreaks.
Meanwhile, the Infectious Diseases Society of America urged the House Oversight & Investigations Subcommittee on Tuesday to support legislation that would provide a 50% tax credit for companies that develop new antibiotics and antifungal drugs designed to treat serious or life-threatening infections that address an unmet need.
But many challenges remain, says Srinivasan. “There is still a lot of need to work on preventing infections from happening in the first place” — things like better infection control programs and more vaccine availability, both within healthcare facilities and the community. And there need to be changes in prescribing behavior.
The CDC plans to release a new resource, Core Elements of Antibiotic Stewardship for Outpatient Practices, later this summer, complementing earlier recommendations for acute care hospitals and nursing homes.
“Simply educating people is probably not going to be the ultimate answer,” says Srinivasan. “It’s an important part of the solution, but what really makes change effective is when you’ve got an infrastructure that helps you support that change.” With all the elements in place, hospitals can look at their antibiotic prescribing system and see where the vulnerabilities are, where the system leads to poor prescribing and how they can fix the system to promote appropriate prescribing, he says.