Keith Kaye, MD, MPH: Successes and Challenges in Addressing MDR Infections

The 2018 IDWeek Annual Meeting in San Francisco, CA, featured a number of sessions, posters, and abstracts highlighting new research on the treatment of multidrug-resistant infections. From new trial data to studies focusing on assessing treatment in various populations, it is clear that multidrug-resistant infections are a key priority for clinicians around the world.

MD Magazine^® sat down with Keith Kaye, MD, MPH, professor of medicine, University of Michigan, to discuss the current successes and challenges in the fight against these infections, as well as expectations for how recommendations will change in the future. [Editor's Note: Transcript slightly modified for readability.]

MD Mag: The concern of multidrug-resistant infections has led to a re-prioritization of clinical research. Can you highlight some of our successes, as well as hurdles, in addressing these infections?

Keith Kaye, MD, MPH: There has been a lot of progress in the past 5 years or so in terms of new agents coming to market that is active against resistant gram-negatives. This has been a great success and a lot of credit goes to the US Food and Drug Administration, as well as the National Institutes of Health for supporting and facilitating the early-stage development of novel compounds.

The fact that we now have safe and effective agents that can treat extremely drug-resistant gram-negatives is almost a miracle. Five years ago, we had very few options, and, in fact, no new and safe ones. There has been a lot of progress.

Unfortunately, there is a lot more work to be done. Bringing new antibiotics to market is not a great business venture for many drug companies; it’s just a fact. We need to find ways to stimulate a continued effort to develop novel agents and continued efforts not only to do standard phase 3 studies but also to do studies like RESTORE, where we targeted what we see to be real-world use of these drugs against very resistant organisms. These are very expensive, complex studies to do.

We’re in need of innovative study designs as well as enhanced attractive draws for the industry to really put the chips in when it comes to investing in new antibiotic development.

To your perspective, in what ways will health care policy, guidelines, and recommendations change in coming years to address the current needs of the infectious disease specialty?

I think we are entering a new age in antimicrobial stewardship. I think people are certainly recognizing how important stewardship is, not only for safety and effective treatments for patients but also for the longevity of antibiotics. No matter how many new antibiotics we create, we are always going to be behind the 8-ball because bacteria were around way before us and they will continue to be around way after we’re gone.

Although we need new agents, we also need new approaches to therapy. Many of our guidelines currently focus on the implementation of stewardship programs and selling the importance of antimicrobial stewardship. As we move forward in the next several years we will be looking at a new age of stewardship where we are much more aggressive in terms of limiting broad-spectrum therapy and shortening duration of therapy. I think we will get more creative with dosing so that we can provide not only shorter courses of therapy but also more potent and high-dose therapies that can limit the emergence of resistance and help to lead to a rapid cure of nasty infections.

The other interesting aspect of stewardship is, traditionally, we focused on the restriction of antibiotic use, de-escalation, and limiting the duration of therapy. We are now entering an age where we have new agents that work against resistant and previous untreatable organisms. We not only have 1 agent; we have several.

Many of these agents have particular niches based on the mechanism of antibiotic resistance. Stewardship is not only going to work on the restriction of antibiotics and limiting inappropriate use, but also helping to identify specifically which of the newer agents, or combination of older agents, will be the most effective not only for any carbapenem-resistant Enterobacteriaceae or Pseudomonas infection, but also for each individual type of resistant gram-negative infections based on patient characteristics and organism characteristics. Those aspects will need to be considered and there will be increasingly defined more specific niches for different, new, important antimicrobials that are active against these nasty pathogens.

It’s a wonderful thing to have more tools in the toolbox; we just have to figure out the best tool to approach each type of challenge and case. That’s a wonderful challenge and opportunity for antimicrobial stewards.