Clinical Considerations for Using Newer Antibiotics for Gram-Negative Infections

This is part of a short series, looking at Gram-negative infections including diagnostics, treatment coordination, and newer agent uptake.

For the uninitiated, when new antibiotics are approved, it might be theorized that these therapies will become widely available and that providers will be able to add them to their armamentariums immediately. However, it is important to point out there is a lot more complexity to adopting new agents and there are careful considerations that need to be weighed before prescribing them, especially in the cases of challenging Gram-negative infections.

Ryan Shields, PharmD, MS, associate professor of Medicine, co-director, Antibiotic Management Program, University of Pittsburgh, says there are 3 main challenges around these prescribing scenarios and using newer agents for these types of infections.

“The first one is education. We've really made resistance and treating resistant Gram-negative infections in particular, quite challenging, and so it's really hard to keep up to date with the most recent evidence, particularly if you're not seeing these infections every day in your clinical practice. They're relatively infrequent, and so oftentimes you feel like you need to catch up. Now this is particularly true even across broad ranges of infectious diseases, but even outside of infectious diseases, keeping up with the latest mechanisms of resistance and new antibiotics that target those mechanisms of resistance, the education is a big lift that we all have to share in our clinical practice,” Shields said. “The second challenge we have is clinical evidence. Oftentimes, these new antibiotics get studied in patient populations that we don't ever really intend to use them in. A good example is maybe a regulatory trial that does a urinary tract infection study amongst generally healthy patients for a new antibiotic that we tend to use in critically ill patients with resistant bloodstream infections or respiratory tract infections. So there's a disconnect there that ultimately has to be filled with clinical experience and real-world data generation, and so until we have some of that additional data, it really is a challenge to know exactly how to use a new antibiotic. The third challenge that I think we all face in this current climate of healthcare is the added emphasis that's on cost. In particular around cost containment, the new antibiotics are several fold more expensive than some of the traditional agents we've been using, and so as stewardship teams and infectious diseases clinicians, we have to justify the added cost of the new antibiotic in terms of what we think it can benefit for patients.”

These challenges inform how Shields prescribes. In terms of data, he really wants to see positive results from studies that examine the intended pathogens in the intended patient populations.

“A recent example of this that kind of speaks to those notes, is sulbactam durlobactam, which there was a clinical study amongst patients with the intended pathogen—in this case, carbapenem-resistant Acinetobacter, and in the intended patient population, those with pneumonia and bloodstream infections,” Shields said. “So even though it was a smaller study, it gave us as clinicians some confidence to say this is a new antibiotic that worked well for the pathogen of interest in the patient population of interest. Now there's more nuance for that. Each of these pathogens has its own challenges and diverse resistance mechanisms, but probably the other way in which we start to favor antibiotics is when we have comparative data, particularly comparative effectiveness data.”
This concludes this series. Look for the other interviews within the sidebar above.