It’s easy to criticize the FDA, whether you think the agency makes it too hard for innovative treatments to help the patients who need them or that Big Pharma holds too much sway over decisions. We’ll avoid that fight and instead focus on why the public, with the FDA’s help, has misunderstood why so many Americans die from resistant infections every year. In short: The Food and Drug Administration focuses on bugs instead of patients.
Only a minority of Americans who die of infections die because the bacteria causing their infections were resistant to antibiotics. Instead, studies show that as many as 95% of Americans who die of infections had treatments that FDA considered effective for them. Yet the focus on rushing new drugs to market is in hopes they will help the 5% instead of helping the 95% survive their infections. Meanwhile, deaths from antibiotic resistance have not increased, but the number of Americans dying from all types of infections has far outpaced those from resistant bugs.
You probably think “antibiotic resistance” means that a bacterial infection can’t be cured by any antibiotics. But the FDA and companies developing new antimicrobial drugs define it as an infection that three or more classes of drugs don’t work for.
Meanwhile, there could be many antibiotics that might be effective for treating infections caused by these bacteria. The definition should depend on how many existing antibiotics are effective, not how many are not. The important point for patients is how many effective drugs remain.
The public understands correctly that MRSA, flesh-eating bacteria, and other potentially deadly bacteria deserve attention and cures. But scary predictions of an epidemic of such deaths are not credible because deaths from MRSA have remained constant over the past decade.
Meanwhile, the FDA has granted approval to a dozen new antibiotics that killed MRSA in a test tube but have not been better at saving patients’ lives (despite the companies’ and FDA’s claims that they were more effective). That’s because the FDA’s approval relied on test tube results, instead of studying the new drugs to see if they improved the lives of patients with MRSA infections.
The focus on killing bacteria in a test tube is misguided for three reasons.
First, antibiotics can save lives even if they kill only most bacteria, not all of them. The human immune system does the rest. Or the drug can kill bugs in the body but patients still die because their immune systems don’t function properly. So what happens in the test tube doesn’t necessarily predict how effective (or not) a drug will be for curing patients.
Second, antibiotics that kill more bacteria sometimes have so many unpleasant side effects (such as nausea, vomiting, and diarrhea) that patients quickly stop taking them. Moreover, antibiotics can have serious side effects that kill patients. For example, the FDA knew that Fetroja increased deaths by 16% compared with older drugs in patients with infections from resistant bacteria but approved it anyway in 2019 as a last resort even though there was clear evidence it was very unlikely to work in patients who did not have other options.
Finally, the patients who die from infections are often older and have immune systems that aren’t functioning as well as they used to. Those patients could survive pneumonia and other infections if their immune system was helped with a steroid or other treatment at the same time they took an antibiotic.
We already have good evidence that thinking outside the box about treating infections can save lives. A study of seriously ill patients in the intensive care unit with pneumonia found that 6% more of those given a common immune-altering steroid while also getting antibiotics were likely to survive than those given antibiotics alone.
But the bigger problem with the FDA’s approach of focusing on killing germs in a test tube is that antibiotics might not actually be the best or only way to fight some infections. Yet the FDA’s attention has been focused on getting more antibiotics to market using “smaller and shorter” studies with less evidence, not better drugs that improve the lives of patients.
Microbiome therapy gives normal bacteria to patients to replace harmful bacteria and was found to reduce diarrhea that can be caused by antibiotics. We need more focus on such non-antibiotic treatments.
The FDA should also approve new antibiotics that are proven to help save the lives of patients with both resistant and susceptible bacterial infections compared to currently available drugs. Did you think the agency already does that? Unfortunately, it doesn’t. Instead, the FDA currently approves drugs based on assumptions from test tube studies instead of studies of patients who would use the drug in the real world. As a result, new drugs may be no more effective than older, cheaper drugs that are already available, even though the new drugs are much more expensive. That has been true for decades, as numerous studies show.
Making America healthy again is a slogan that appeals to many medical professionals and the public. New approaches to reducing common infections that will help patients live longer is a good place to start.
Diana Zuckerman, Ph.D., is president of the National Center for Health Research and a former congressional investigator on FDA approval standards. John H. Powers III, M.D., is professor of clinical medicine at George Washington University School of Medicine and professor in the Department of Pharmaceutical Health Services Research at University of Maryland School of Pharmacy.