Superbugs rising

It's a parent's worst nightmare. Your healthy child is suddenly ill. The doctors you've trusted to treat him are unable to do anything about it. Drugs that we've relied upon for decades are becoming increasingly useless as bacteria evolve resistance to them. New drugs are few and far between. Old drugs, shelved because of their toxic side-effects, are being brought in as last resorts--kidney failure, after all, is better than certain death.

Unfortunately, this is increasingly the state of medicine today, and people are dying from it. The World Health Organization even recently sounded the alarm, noting that "the world is headed for a post-antibiotic era"--and it takes a lot of consensus to get the WHO to act, so this is a Big Deal.

I was in Washington, DC last week for two days to discuss the issue with other "supermoms" and dads (farmers, physicians, researchers, and parents whose children had experienced antibiotic-resistant infections), and to share information with legislators and government agencies. (I also brought William, 4 months old, for an extra dose of adorableness).

Superbabies against Superbugs Superbabies against Superbugs

Some of the "super" attendees might be familiar to readers. I had the pleasure of meeting Russ Kremer, who has been profiled in several articles and documentaries. Russ raised pigs in confinement, dosing them with antibiotics from birth to slaughter until he was gored by a boar, resulting in a very difficult-to-treat infection that almost cost him his life. David Ricci was also present. His story was profiled in the Frontline documentary, "Hunting the Nightmare Bacteria." He contracted an infection with bacteria carrying the NDM-1 genes, making them resistant to almost all known antibiotics, and required multiple surgeries and treatment with some of these last-line drugs over many months.

There were also participants you may not have read about previously, like Amanda Hedin and Everly Marcario, who both lost children to antibiotic-resistant infections. I've written before about the immense sadness that comes at times when studying infectious disease, noting that I have a freezer full of bacterial isolates that, while important for study, frequently mark someone's illness or death. It's important work, but heart-wrenching at times.

However, we have very little funding to study such infections. My colleague Eli Perencevich recently estimated the amount of money spent on antibiotic-resistant infections versus HIV/AIDS, and the answer is that it's vastly less. Antibiotic resistance needs to be a priority on many fronts. The FDA has recently made some headway into possibly reducing antibiotic use on farms, though optimism is mixed regarding how much that will actually help things. Hospitals and clinics are working with physicians to encourage and enforce best practices for antibiotic prescribing in these settings.

We need to be responsible with antibiotics. Drugs in development are scarce, and none are ready for prime time. It's almost unimaginable that we may return to a time when an infected scrape could mean the death of a healthy young man, but we're closing in on that every day. The WHO wrote in their report:

“A post-antibiotic era, in which common infections and minor injuries can kill, far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century.”

We need action, not promises. And we need it now.

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Do you have links to studies showing if/how resistance will be reduced as agricultural antibiotic usage drops? How much of a fitness cost do the antibiotic resistance genes carry in the absence of antibiotics? What kind of reductions in usage will we need in order to cut down on antibiotic resistance?

By Joe McPhee (not verified) on 13 May 2014 #permalink

It's complicated and dependent on the species of bacteria and type of antibiotic. When Europe banned the use of avoparcin (a glycopeptide) in poultry, vancomycin-resistant enterococci went down in humans. (see http://jac.oxfordjournals.org/content/46/1/146.full for example). In Quebec, when they stopped using ceftiofur in chickens, they saw a similar decrease in resistance in Salmonella (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874360/). In other cases, yes, resistance can persist even in absence of antibiotics, like fluoroquinolone resistance in Campylobacter (http://www.ncbi.nlm.nih.gov/pubmed/15866763) but even maintaining the status quo and not *increasing* resistance further with continued use would be better than nothing.

Interesting - does the ability to decrease resistance following pulling the antibiotic vary depending in the plasmid that contains the resistance cassettes? One could imagine a'bic resistance genes getting into plasmids that also carry virulence determinants - in that case, I'd predict that the resistance would stick around because of the benefits of the other virulence genes. The bacteria I study (a clinical isolate) has loads of antibiotic resistance determinants but is quite stable in long term animal colonization.

By Joe McPhee (not verified) on 15 May 2014 #permalink

Yep, that's part of it, again, depending on species yada yada. For instance, in Staph aureus I look at methicillin-resistant bugs on the farm, but methicillin itself isn't actually used in farming. So resistance is selected because of penicillin use, and because of other genes which co-localize with the methicillin resistance (mecA) gene. There's also some interesting research suggesting that even zinc use, which has increased in some parts of Europe following a ban on growth-promoter antibiotics, has driven the emergence/persistence of methicillin resistance, again probably due to the resistance genes being on the same cassette.

So basically - we're screwed? Could one develop a compound(s) to encourage plasmid loss? I know there are some topoisomerase inhibitors that can do this - but I wonder about developing ones that are less toxic and that could be used to address the resistance reservoir?

By Joe McPhee (not verified) on 16 May 2014 #permalink

Well, I'm more optimistic than that. I know there is research going on into some of those areas but I have no idea how successful it's been or what the downsides might be. Obviously there's also a lot of research into different compounds--new antibiotics, things like phage lysins, etc. but as mentioned, none of those are ready for prime time.

Have you come across/ Are you familiar with Dr. Martin Blaser at NYU? In his book, he talks about the importance of reducing antibiotic usage and preserving our microbiota from a young age. Its a fascinating read. I'd be curious as to what you think of his work.

Yep. I have his new book and will review it here in the next few weeks.