Stack this concern about extra hospital use, and the resistance it will likely provoke, on top of uncontrolled community use. The antibiotic azithromycin is half of the indie preventive treatment (along with hydroxychloroquine) that was promoted by a physician in France, took off across Silicon Valley, and was pushed relentlessly by the White House and Fox News. There is little evidence this combo works: Just this week, a new preprint study from researchers at the Columbia VA Health Care System in South Carolina, the University of South Carolina and the University of Virginia showed that hydroxychloroquine not only doesn’t protect against Covid-19, but is associated with higher rates of death. (This study is considered preliminary: As a preprint, it has not yet been through peer review or published in a medical journal.)
Nevertheless, according to the Food and Drug Administration, there has been such a spike in azithromycin use that nine different manufacturers have reported shortages they cannot resolve for months.
Azithromycin isn’t the only antibiotic being put to nonstandard use for Covid-19. New papers and preprints show that physicians are experimenting with amoxicillin, tetracycline, doxycycline, and teicoplanin, a last-resort drug used against MRSA, to try to prevent coronavirus infections. That all adds up to vast amounts of excess use, and to enhanced risks of resistance emerging and undermining the power of those drugs.
That’s a problem, because resistance is already potent: In parts of the US, the major bacterial cause of pneumonia defeats the first-choice antibiotic used for it more than half the time. It’s equally a problem because so few new drugs are available to replace them. Last week, the Pew Trusts released new data showing that antibiotic development is fragile: More than half of the new drugs in the pipeline are still in Phase 1 or 2 trials, putting them years from approval. All but one of the firms developing new drugs are small biotechs with little cash on hand to survive the time it will take to get there.
“We don’t have the variety of antibiotics we need, we don’t have the novelty of mechanisms we need, we don’t have enough addressing the World Health Organization’s priority pathogens,” Talkington says.
No one is arguing that antibiotics should be withheld from patients who need them. (Though dialing down outside-hospital use by the worried well who are using them as a preventative would be a good thing.) The problem instead is how to strengthen drug development so that new antibiotics are available if increased use pushes resistance to new heights. That’s proved a challenge so far.
In addition to its sky-high annual death toll, antibiotic resistance incurs enormous costs: The CDC estimated in 2013 that resistant bacteria require the US alone to spend $20 billion extra on healthcare each year. Yet the problem hasn’t sparked the public policy response that the new coronavirus has. In fact, one bipartisan proposal to get a small amount of additional funding to drugmakers, by increasing the Medicare reimbursement rates of hospital antibiotic purchases, was taken out of the first pandemic stimulus bill.
Just last year, two promising antibiotic companies, Melinta Therapeutics and Achaogen, entered bankruptcy despite having gotten their drugs through the FDA. Since 2000, most of the big legacy drug firms that once made antibiotics have stopped. If coronavirus care makes resistance worse, taking more antibiotics out of circulation, that could encourage the few remaining firms to leave.
The vast international mobilization to do something about the new coronavirus—identify existing drugs, work up new treatments, achieve a vaccine—might paradoxically offer hope for antibiotic research. The enormous amount of work being launched shows that money and purpose can be marshalled against a threat, if the threat seems dire enough. In 2014, a UK government report predicted that deaths from antibiotic resistance could reach 10 million per year worldwide by 2050. That certainly seems dire.
“I’m hoping that once we get out of this, we’ll have a new appreciation of how vulnerable we are to infections, whether that’s new viruses or bacterial infections or resistant fungi on a cancer ward,” says Gerry Wright, a microbiologist and drug discoverer, and director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University, “and that we really need to invest in new drugs and vaccines in advance, and that policy makers will hear that and take some action.”
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