Why Are Researchers Struggling to Develop Effective Antibiotics?

Barry Kreiswirth, PhD, founding director, Public Health Research Institute Tuberculosis Center, professor of medicine at Rutgers University, examines the difficulty of developing new, effective antibiotics as more and more bacteria continue to develop resistance.

Interview Transcript (slightly modified for readability)

“It’s very interesting what’s happened over the years. We’ve gone from, obviously, the major boom in the pharmaceutical industry was broad-spectrum antibiotics: [a] patient comes in, you’re not sure what they have, [if] they have a gram-negative infection [or] a gram-positive infection, [so] I give them a broad-spectrum [agent] that covers everything; it’s a wonder drug. That’s what we did historically, and because of that, we’ve sort of backed ourselves in[to] a corner that once one of the bacteria become resistant to that [antibiotic], all of a sudden, that broad-spectrum agent doesn’t have such a broad spectrum [anymore]. What you end up starting to do is, you start filling in the gaps with narrow-spectrum [antibiotics]. Now, the bugs have become so resistant, that the broad agents don’t work anymore.

This is a problem with the pharmaceutical industry because, if you’re [in] the pharmaceutical industry, the broad-spectrum drugs make a lot more money than a narrow-spectrum drug, because you can use them on almost any patient who walks in. The fact that [we’re having] so much resistance now [lends to the idea that] the narrow-spectrum drugs are what we have to make; obviously, their use is less, their ability to actually work [has] become more problematic because they’re focused on very drug-resistant strains, [which] have the ability, just because they basically have been exposed to so many different antibiotics, [to] develop resistance quite quickly.

The one thing we’d love to do is to develop what we call novel agents, which means a whole new family of agents; [that’s] just very hard to do. The pharmaceutical companies, they’re good at what they do, they’ve done this for a long time; the idea that they can just snap their fingers and just say, ‘okay we’ll come up with a different strategy,’ [is difficult because] they’ve basically exhausted a lot of compounds that are out there. So, even [when] revisiting old drugs, which is something we do, we still find ourselves trapped in this idea, but resistance really is still going to thwart this new compound, mainly because these bugs have seen this compound, just in a different version; it’s not like they haven’t been exposed to this—they have, but it’s not exactly the same thing– but it’s related enough [that] the bacteria actually have [a] resistance mechanism.

It’s quite frustrating for the pharmaceutical industry just because the challenge is so high, mainly because we’ve created this problem. The sad thing is the bacteria that we’re going to encounter today is not much different than the bacteria that our grandparents encountered, [for example], 60 years ago; the difference is that bacteria is now drug-resistant.

The [idea behind] superbugs is not that the bacteria [have] become more virulent, it’s just that we can’t treat them as well as we could years ago because we don’t have the same agents that [were once] available [to us].”