At this point, alarmist headlines about the end of the antibiotic era may seem a lot like those car alarms that periodically go off on your street: distracting, annoying, and probably nothing worth panicking over. After all, despite years of distressing headlines, drug-resistant superbugs have yet to rain down upon the public, striking the otherwise healthy with deadly, incurable infections.

Yet, the unfortunate reality is that the longstanding challenge of drug resistance is cause for concern and action. Bacteria have been developing resistance to powerful antibiotics ever since the drugs were first introduced in the 1930s. In some cases, bacteria developed widespread resistance in years and sometimes months after a new drug came out. And bacteria are building up ever more extensive immunity thanks to current practices of overusing and misusing the drugs—antibiotics given thoughtlessly for mild illnesses, or used to treat viral infections (which antibiotics don’t fight), or poured into the feed of healthy livestock. Coupled with the sluggish development of new drugs in the past few decades, the public health problem has reached a crisis level.

Right now, drug resistant infections are mainly a threat to those that are already sick and/or in medical facilities. But, if we continue down this path, mundane infections in the otherwise healthy could someday morph into life-threatening ordeals, and simple medical procedures and surgeries may be skipped to avoid risk of infection.

However, while this threat is real, it’s important to keep in mind that this is an ongoing, gradual challenge; it’s extremely unlikely that a single event will herald with complete certainty the abrupt end of modern medicine as we know it. In this context, those scary headlines are inappropriate, if not numbing and counterproductive.

In May, Ars wrote about some alarmist and inaccurate news stories dealing with a newly identified type of drug resistance—one that makes bacteria resistant to a last-resort antibiotic called colistin and can spread between bacteria easily. The headlines blared that it was the “first” time such a dastardly microbe had seeped into the US—which is not true. And they suggested that it would certainly mark the end of antibiotics—also not true.

This week, scientists provided updates on tracking that type of resistance, and of course some alarmist headlines followed. Yet, the new data actually suggests that a tempering of concerns about this particular resistance may be in order. It turns out that this “dreaded,” "scary," “nightmare” of a drug-resistant microbe has been in the US for more than a year and elsewhere in the world since as far back as 2005—it’s just that nobody noticed it. And nobody noticed it because so far it hasn’t been the dreaded, scary nightmare some have feared.

“It’s not a huge cause for concern,” Mariana Castanheira, lead author of one of this week's resistance updates, told Ars. Castanheira is the director for Molecular and Microbiology at JMI Laboratories, a private company that monitors drug resistance microbes in hospitals and medical settings. They and others are finding this new type of resistance now simply because they’re looking for it, she said.

Castanheira explains that people initially started digging for this new type of drug resistance—a gene called mcr-1—out of concern that it makes bacteria resistant to the antibiotic colistin, which is a relatively toxic drug used only when nearly all others have failed against a multi-drug resistant infection. Bacteria have shown up with colistin resistance before—in fact, many times in the US and elsewhere around the world. But in those cases, the genes were embedded in the bacteria’s chromosomes and generally passed down through generations. The mcr-1 resistance gene, on the other hand, seems to always sit on a plasmid, a small loop of DNA that bacteria can readily pass around to neighbors. If colistin-resistant bacteria shared their mcr-1 plasmid with others that are already resistant to lots of antibiotics, they could create a long-feared invincible germ—a “pan-resistant” bacteria.

"Doesn't scare me"

So far that doesn’t seem to be happening, though, Castanheira said. In more than a decade of skulking around, mcr-1 has made its way into bacteria in animals, people, and soil all over the world. Yet, all of the mcr-1 carrying microbes examined have been susceptible to at least one antibiotic—and often several.

In Castanheira’s new study, published Monday in the journal Antimicrobial Agents and Chemotherapy, she and colleagues tested 13,526 E. coli and 7,480 Klebsiella pneumoniae clinical strains collected in 2015 from hospitals and clinics worldwide—including the Asia-Pacific region, to Latin America, Europe, and North America. Tests showed that 390 bacterial isolates, or 1.9 percent, were resistant to colistin. Of those, 19 had mcr-1-based colistin resistance.

The 19 came from 10 countries, representing all regions of the world. One of them was from the US, isolated from a patient in New York in May of 2015—months before colistin resistance was first reported in China. This mcr-1-toting New York isolate was susceptible to several commonly used antibiotics, as were the other 18 mcr-1-containing isolates. They were not the pan-resistant superbugs researchers feared.

In addition to Castanheira’s study, there are other new reports from the US and around the world of cases of mcr-1 and variants of mcr-1—which are plasmid-based genes that make bacteria resistant to colistin but have slight DNA tweaks compared to mcr-1. Those genes also seem to be spreading around undetected and not causing major problems.

Why it’s around but not wreaking mass destruction is unclear. It may be that the mcr-1 plasmids are a burden for microbes to carry around. Thus, in an environment like the human gut, where there’s a lot of microbial competition for food and space, microbes may simply ditch the colistin resistance. “The stability and transferability of the mcr-1-bearing plasmids may be low and those plasmids do not harbour many other antibiotic resistance genes,” a pair of Swiss researchers recently speculated in a published commentary.

Still, one new report suggests that the worse-case scenario might not even be that bad. On Monday, Italian researchers reported that they found a bacterial isolate with mcr-1-based colistin resistance and resistance to carbapenems, another last-resort treatment. Carbapenem resistance is a significant concern because it has been rising steadily in recent years. When bacteria in the Enterobacteriaceae family, which includes Salmonella, E.coli, Klebsiella, and Shigella, become resistant to carbapenems the infections they cause can lead to death 50 percent of the time. For this reason, these CRE infections (carbapenem-resistant Enterobacteriaceae) are particularly feared. Right now, they’re often treated with colistin.

The Italian study, also published in Antimicrobial Agents and Chemotherapy, describes a Klebsiella strain with a variant of mcr-1 colistin resistance and carbapenem resistance that was swabbed from the rectum of a boy with leukemia back in 2014. Like the other mcr-1-carrying bacteria so far, 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 bacterium wasn’t causing an infection. It was harmlessly colonizing the boy, the Italian researchers report.

Still, even if it was causing 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 doesn’t seem to produce strong resistance to colistin, suggesting that some dosages and combinations could still be effective against the infections.

In a May interview with NBC News about the “scariness” of mcr-1, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, replied:

"It doesn't scare me. I think when you use the word scare that just adds a degree of emotional response to it that is not appropriate. This is a challenge we have. We know that we have an issue with antibiotic resistance. We have it and have had it in this country and worldwide for some time now."

What we need instead of fear, Castanheira said, is international efforts to curb unnecessary use of antibiotics, particularly colistin, and to incentivize the development of new drugs.

Antimicrobial Agents and Chemotherapy, 2016. DOI: 10.1128/AAC.01267-16 (About DOIs).