Antibiotic resistance: The last resort
As a rule, high-ranking public-health officials try to avoid apocalyptic descriptors. So it was worrying to hear Thomas Frieden and Sally Davies warn of a coming health “nightmare” and a “catastrophic threat” within a few days of each other in March.
The agency heads were talking about the soaring increase in a little-known class of antibiotic-resistant bacteria: carbapenem-resistant Enterobacteriaceae (CREs). Davies, the United Kingdom’s chief medical officer, described CREs as a risk as serious as terrorism (see Nature 495, 141; 2013). “We have a very serious problem, and we need to sound an alarm,” said Frieden, director of the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
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Their dire phrasing was warranted. CREs cause bladder, lung and blood infections that can spiral into life-threatening septic shock. They evade the action of almost all antibiotics — including the carbapenems, which are considered drugs of last resort — and they kill up to half of all patients who contract them. In the United States, these bacteria have been found in 4% of all hospitals and 18% of those that offer long-term critical care. And an analysis carried out in the United Kingdom predicts that if antibiotics become ineffective, everyday operations such as hip replacements could end in death for as many as one in six1.
The language used by Davies and Frieden was intended to break through the indifference with which the public usually greets news about antibiotic resistance. To close observers, however, it also had a tinge of exasperation. CREs were first identified almost 15 years ago, but did not become a public-health priority until recently, and medics may not have appreciated the threat that they posed. Looking back, say observers, there are lessons for researchers and health-care workers in how to protect patients, as well as those hospitals where CREs have not yet emerged.
“It is not too late to intervene and prevent these from becoming more common,” says Alexander Kallen, a medical epidemiologist at the CDC. At the same time, he acknowledges that in many places, CREs are here for good.
More on antibiotics:Farming up trouble
Hindsight is key to the story of CREs, because it was hindsight that identified them in the first place. In 2000, researchers at the CDC were grinding through analyses for a surveillance programme known as Intensive Care Antimicrobial Resistance Epidemiology (ICARE), which had been running for six years to monitor intensive-care units for unusual resistance factors. In the programme’s backlog of biological samples, scientists identified one from the Enterobacteriaceae family, a group of gut-dwelling bacteria. This particular sample — of Klebsiella pneumoniae, a common cause of infection in intensive-care units — had been taken from a patient at a hospital in North Carolina in 1996 (ref. 2). It was weakly resistant to carbapenems, powerful broad-spectrum antibiotics developed in the 1980s.
Antibiotics have been falling to resistance for almost as long as people have been using them; Alexander Fleming, who discovered penicillin, warned about the possibility when he accepted his Nobel prize in 1945. Knowing this, doctors have used the most effective drugs sparingly: careful rationing of the powerful antibiotic vancomycin, for example, meant that bacteria took three decades to develop resistance to it. Prudent use, researchers thought, would keep the remaining last-resort drugs such as the carbapenems effective for decades.
The North Carolinan strain of Klebsiella turned that idea on its head. It produced an enzyme, dubbed KPC (for Klebsiella pneumoniae carbapenemase), that broke down carbapenems. What’s more, the gene that encoded the enzyme sat on a plasmid, a piece of DNA that can move easily from one bacterium to another. Carbapenem resistance had arrived.