Though there has been tremendous progress in antibiotic stewardship efforts over the last decade, a broad and demanding array of research and action is needed if the rise of drug-resistant bacterial infections is to be stemmed, the Society for Healthcare Epidemiology of America (SHEA) reports in a new white paper.1

Lead author Andrew Morris, MD, chair of the SHEA Antimicrobial Stewardship Committee, dispenses with the platitudes on progress and sees the threat for what it is, an advancing siege on the miracle of antibiotics.

“We should be treating antibiotics like narcotics,” he tells Hospital Infection Control & Prevention. “For every single antibiotic, [report] who is getting it, and when and how are they getting it.”

Morris continues, in what sounds like a strategic goal for the distant future. “Ideally, this would be paired with microbiology,” he says. “It would set up an accountability framework, but more importantly, it would establish systems that would facilitate both epidemiological studies as well as intervention and implementation studies.”

Of course, such stringent controls are largely absent in a U.S. healthcare system that has erred historically on the side of dispensing antibiotics whether they are needed or not. That is changing, but Morris, a self-described “antibiotic steward,” underscores the magnitude of the current problem.

“We know that there aren’t enough antibiotic stewards in the U.S. probably to [address] the state of California,” he says. “Even if we wanted to take everybody from across the country and steward [antibiotics] in the state of California - [think of] all the locations where antibiotics are prescribed, long-term care, ambulatory care. There’s not a chance. We have to figure that out - and we won’t in the near future.”

Currently, physicians and pharmacists primarily lead antibiotic stewardship programs, which attempt in part to temper and calibrate antibiotic use so that the drugs simply do not kill off the susceptible bacteria and select our drug-resistant pathogens. The end result of that process can be pan-resistant pathogens. For example, a hospitalized patient in Reno, NV, died in 2016 of a carbapenem-resistant Enterobacteriaceae (CRE) strain that was impervious to 26 antibiotics.2 

“Antibiotic-resistant bacteria infect 2 million Americans annually, resulting in up to 100,000 deaths and excess healthcare costs exceeding $20 billion,” the SHEA paper states. “Antibiotic use is a major contributor to antibiotic resistance, infections, and antibiotic-associated adverse events. Antibiotics are frequently used across all healthcare settings in the United States, although much of this use is unnecessary.”

The Emerging IP Role

The paper sets out a daunting array of research needs, but, as a practical matter, calls for heightened awareness of stewardship and knowledge that is wired in all the way from physicians down to bedside care. “I think there is a huge role for IPs to be involved in antibiotic stewardship efforts,” Morris says, “even though some of the things we traditionally consider stewardship are going to be outside their scope of practice. That doesn’t mean they can’t be involved in stewardship of antibiotics.”

Indeed, many IPs have been involved in successful efforts to reduce Clostridioides difficile infections, a common patient outcome of antibiotic disruption of commensal bacteria in the gut. One such effort focused on hand hygiene, environmental cleaning, and reducing the overuse of broad-spectrum drugs and inappropriate stool testing that may trigger unneeded prescriptions. (See Hospital Infection Control & Prevention, December 2017.) Similarly, IPs have been involved in sparing patients with asymptomatic bacteriuria from unnecessary treatment more appropriate for a urinary tract infection (UTI).

“A lot of antibiotic decisions are actually not made by the prescriber,” Morris says. There are opportunities to communicate and break “cycles of behavior” where the default position is antimicrobial treatment. “You don’t need to be a physician or a pharmacist to help change that behavior,” he says.

To research the paper, Morris and colleagues convened a diverse, multidisciplinary group of stewardship clinicians and researchers to identify research gaps from a U.S. human health perspective. They condensed this to four research priorities:

  • development of evidence supporting best clinical practices in a variety of settings and patient populations (i.e., what to do);
  • assessment of optimal approaches to implement stewardship practices in diverse settings, with a focus on behavioral change, sustainability, and personnel (i.e., how best to do it);
  • development of standardized, valid, and reliable process and outcome metrics to support stewardship efforts, supported by information technology infrastructure and analytics (i.e., how to measure what you are doing);
  • development of approaches to advanced study design with appropriate analytic methods (i.e., how to determine effective methods to continually improve stewardship practices).

Q & A

HIC talked to Morris, medical director of antibiotic stewardship for the Sinai Health System Toronto, on other aspects of the paper in the following interview, which has been edited for length and clarity. Morris also chairs the Antimicrobial Stewardship Working Group for Accreditation Canada.

HIC: Can you comment on the success (or lack thereof) of stewardship efforts over the last few years?

Morris: I think we are much better than we were 10 years ago because actions are being taken, policies are being developed, research is being done. We are starting to understand the problem better. The pace of improvement in all of those areas has actually been fairly rapid. However, because we did not delve into the issue in full earnest until maybe 10 to 15 years ago, we are really behind the eight-ball. There is a lot we don’t know. There are so many areas we don’t have full knowledge of what the best thing to do is. Or where we are even at. We don’t have very good data systems to help us. Eighty to 90% of antibiotics used in the U.S. are out in the community. We don’t have a great understanding of the overall burden of antibiotic resistance and antibiotic use.

HIC: There are some data suggesting reduced use fluoroquinolones, a known trigger for C. diff infections.

Morris: There is no question that fluoroquinolone use has decreased dramatically. There has been a major drop. But it is like the metaphor of squeezing the balloon. Fluoroquinolone use dropped, but all the other classes went up. The problem we have is that we are addicted to antibiotics. It’s actually very easy to get prescribers to stop prescribing a drug or a group of drugs. But what we can’t get them to reduce is the overall use antibiotics. There hasn’t been much of an overall change of antibiotic use across the country.

HIC: Many hospitals have established stewardship programs, but you mention the staggering level of antibiotic use in outpatients.

Morris: There are substantial gaps outside of hospitals - all kinds of ambulatory care and that includes emergency departments and long-term care facilities. There is a huge opportunity to improve antibiotic prescribing in those areas. There is a lot of prescribing in those areas and very little [stewardship] work has been done. We don’t have the researchers and data systems and networks there. They are among the areas that we think you are going to get the biggest bang for the buck. Another one of them is going to be improving how we study antibiotic use, so improving the design and method [of research].

HIC: Why is it so important to do this new research and why is it so challenging?

Morris: Many people may not realize it, but infectious disease studies, particularly as they relate to resistance and antibiotics, are entirely different than any other disease. Aspirin for heart attacks worked in the 1950s the same way it works in 2019. Penicillin for UTIs in 1950 is entirely different than penicillin for UTIs in 2019. These things are dynamic, and not only in terms of efficacy and the way it affects the population. Giving one patient an aspirin makes no difference to the person next to them. If you give a patient an antibiotic it absolutely can make a difference for other patients. These things are key in differentiating this kind of research from anything else. There are time and population-based factors that are not seen anywhere else. Measuring all those things is also very difficult. We sort of know how to measure antibiotics, but not really. It actually makes a difference whether you talk about the day of treatment vs. how many milligrams or how many doses. It also makes a difference because of the population and the time factors. It doesn’t make much of a difference if a patient gets aspirin for five days or two weeks. But it absolutely makes a difference if we are talking about somebody getting two weeks of amoxicillin. Those things make a huge difference.

HIC: There are certainly unknowns and research needs, but you note that we have failed to address even known factors in some sense.

Morris: Yes, once we know what the best thing to do is - how do we actually make that happen? For example, there is not a doctor in the country who doesn’t recognize that we shouldn’t be treating viral infections with antibiotics. Similarly, there isn’t a doctor in the country who doesn’t recognize that most colds are viral. Despite that, many, many patients have colds and are being treated with an antibiotic. How do we change that? It’s not a matter of getting the best evidence for treatment. It’s a behavioral change implementation science issue, whether it is a way of locking down [the formulary] so they can’t prescribe in those situations or focusing on [expectations of] patients and their families, or whether we need to do this with better diagnostics.

HIC: You cite emotional factors driving some antibiotic misuse, such as the clinicians’ fear of the “worst-case scenario” and their desire to avoid conflict with a demanding patient. What about cases where the physicians must balance the needs of the individual patient vs. the larger harm of antibiotic resistance to society?

Morris: That paradox is often referred to as the “tragedy of the commons” in ethical principles. The truth is [with antibiotics] it is primarily a false narrative. It is extremely rare that it is what is best for the patient vs. what is best for society. That’s rare. The problem is that people don’t have the necessary information in terms of risks. When a patient actually understands the full potential risks of antibiotic treatment for a viral infection, they would actually say, “I don’t want it.” Most people, if you offer them two burgers - one where the cow has not been fed antibiotics and one where the cow has been stuffed with antibiotics - they are going to choose the one without antibiotics. People know. It’s not really an issue of people thinking it’s good to take antibiotics. It is all how it is framed. The question is almost always what is best for the patient, but do [they understand by taking an antibiotic] they are taking the chance of getting C. difficile, a yeast infection, a drug-resistant organism, an adverse drug reaction, diarrhea, rash, and anaphylaxis? Most people - if they know that information - will change their choice.

REFERENCES

  1. Morris AM, Calderwood MS, Fridkin SK, et al. SHEA white paper: Research needs in antibiotic stewardship. Infect Control Hosp Epidemiol 2019;1-10. doi:10.1017/ice.2019.276. [Epub ahead of print].
  2. Chen L, Todd R, Kiehlbauch J, et al. Notes from the field: Pan-resistant New Delhi metallo-beta-lactamase-producing Klebsiella pneumoniae — Washoe County, Nevada, 2016. MMWR Morb Mortal Wkly Rep 2017;66:33.