A cluster of E. coli bacteria.
Right now, alarming headlines about the end of the antibiotic era might be a lot like those car alarms that occasionally go off on your street: distracting, annoying, and probably nothing worth panicking about. After all, despite years of disturbing headlines, drug-resistant superbugs have yet to descend on the public, striking the otherwise healthy with deadly, incurable infections.
Yet the unfortunate reality is that the long-standing challenge of drug resistance is cause for concern and action. Bacteria have been developing resistance to potent antibiotics since the drugs were first introduced in the 1930s. In some cases, bacteria developed widespread resistance years and sometimes months after a new drug hit the market. And bacteria are building up ever-expanding immunity thanks to current practices of drug overuse and abuse—antibiotics thoughtlessly given for mild illnesses, or used to treat viral infections (which antibiotics don’t fight), or in the feed of healthy cattle are cast. Coupled with the slow development of new drugs in recent decades, the public health problem has reached a crisis level.
Currently, drug-resistant infections mainly threaten those who are already sick and/or in medical facilities. But if we continue down this path, everyday infections in otherwise healthy people could one day turn into life-threatening trials, and simple medical procedures and surgeries could be skipped to avoid the risk of infection.
While this threat is real, it’s important to keep in mind that this is an ongoing, gradual challenge; it is extremely unlikely that a single event will, with complete certainty, herald the abrupt end of modern medicine as we know it. In this context, those creepy headlines are inappropriate, if not numbing and counterproductive.
In May, Ars wrote about some alarming and inaccurate news stories about a newly identified type of drug resistance — one that makes bacteria resistant to a last-resort antibiotic called colistin and can easily spread between bacteria. The headlines screamed that it was the “first” time such a vicious microbe had seeped into the US – which is not true. And they suggested that it would definitely mean the end of antibiotics – also not true.
This week, scientists provided updates on tracking that kind of resistance, and of course some alarming headlines followed. Still, the new data actually suggests that some moderation of concerns about this particular resistance might be in order. As it turns out, this “dreaded,” “creepy,” “nightmare” of a drug-resistant microbe has been in the U.S. for over a year and elsewhere in the world since 2005 — it’s just that no one noticed. And no one has noticed, because until now it hasn’t been the dreaded scary nightmare some feared.
“It’s not a major cause for concern,” Mariana Castanheira, lead author of one of this week’s Resistance updates, told Ars. Castanheira is the Director of Molecular and Microbiology at JMI Laboratories, a private company that monitors drug-resistant microbes in hospitals and medical settings. She and others are now finding this new type of resistance simply because they’re looking for it, she said.
Castanheira explains that initially people started digging for this new type of drug resistance – called a gene mcr-1– out of concern that it may make bacteria resistant to the antibiotic colistin, a relatively toxic drug used only when nearly all others have failed against a multidrug-resistant infection. Bacteria with colistin resistance have popped up before — in fact, many times in the U.S. and elsewhere in the world. But in those cases, the genes were embedded in the bacteria’s chromosomes and generally passed down from generation to generation. The mcr-1 resistance gene, on the other hand, always seems to be on a plasmid, a small loop of DNA that bacteria can easily pass on to neighbors. If colistin-resistant bacteria shared their mcr-1 plasmid with others already resistant to many antibiotics, they could create a long-dreaded invincible germ – a “pan-resistant” bacteria.
“Don’t Scare Me”
So far, however, that doesn’t seem to be happening, Castanheira said. In over a decade of sneaking around, mcr-1 has found its way into bacteria in animals, humans and soil around the world. Yet all mcr-1 carriers of microbes under investigation have been susceptible to at least one antibiotic – and often several.
In Castanheira’s new study, published Monday in the journal Antimicrobial agents and chemotherapyshe and colleagues tested 13,526 E coli and 7,480 Klebsiella pneumoniae clinical strains collected in 2015 from hospitals and clinics around the world, including the Asia-Pacific region, Latin America, Europe, and North America. Tests showed that 390 bacterial isolates, or 1.9 percent, were resistant to colistin. Of these, 19 had mcr-1-based colistin resistance.
The 19 came from 10 countries, representing all regions of the world. One came from the US, isolated from a patient in New York in May 2015 – months before colistin resistance was first reported in China. This mcr-1-The New York isolate was susceptible to several commonly used antibiotics, as were the other 18 mcr-1-containing isolates. It wasn’t the pan-resistant superbugs that researchers feared.
In addition to Castanheira’s study, there are other new reports from the US and around the world of cases of pneumonia mcr-1 and variants of mcr-1– these are plasmid-based genes that make bacteria resistant to colistin, but compared to minor DNA modifications mcr-1. Those genes also seem to spread unnoticed and not cause any major problems.
Why it is there but not causing mass destruction is unclear. It may be that the mcr-1 plasmids are a burden for microbes to carry around. So in an environment like the human gut, where there is a lot of microbial competition for food and space, microbes can simply kill colistin resistance. “The stability and transferability of the mcr-1-carrying plasmids may be low and those plasmids do not contain many other antibiotic resistance genes,” a pair of Swiss researchers recently speculated in a published commentary.
Still, a new report suggests the worst-case scenario may not even be that bad. Italian researchers reported on Monday that they had found a bacterial isolate in mcr-1-based colistin resistance And resistance to carbapenems, one last resort. Resistance to carbapenem is a major concern, as it has been steadily increasing in recent years. When bacteria in the Enterobacteriaceae family, including Salmonella, E coli, KlebsilAnd Shigella, become resistant to carbapenems, the infections they cause can lead to death in 50 percent of cases. For this reason, these CRE infections (carbapenem-resistant Enterobacteriaceae) are particularly feared. At the moment, they are often treated with colistin.
The Italian study, also published in Antimicrobials and Chemotherapy, describes one Klebsil tribe with a variant of mcr-1 colistin resistance and carbapenem resistance taken from the rectum of a boy with leukemia in 2014. Just like the others mcr-1-carrying bacteria until now, it was still susceptible to several antibiotics despite also being resistant to carbapenems. However, the point is moot because this colistin-resistant, carbapenem-resistant, doomsday bacteria did not cause an infection. It colonized the boy in an innocent way, the Italian researchers report.
But even if it caused an infection and was resistant to all common antibiotics, colistin isn’t really the end of the antibiotic line, Castanheira said. Last year, the Food and Drug Administration approved a new antibiotic combination drug called Avycaz that is expected to be useful for treating CRE infections. Also, mcr-1 does not appear to produce strong resistance to colistin, suggesting that some dosages and combinations may still be effective against the infections.
In a May interview with NBC News about the “anxiety” of mcr-1, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, responded:
“It doesn’t scare me. I think when you use the word startle it just adds a level of emotional response that isn’t appropriate. This is a challenge we have. We know we have a problem with antibiotic resistance. We’ve got it and have had it for a while in this country and worldwide.”
What we need instead of fear, Castanheira said, are international efforts to curb unnecessary use of antibiotics, especially colistin, and to boost the development of new drugs.
Antimicrobial agents and chemotherapy2016. DOI: 10.1128/AAC.01267-16 (About DOIs).