Bacterial populations are normally viewed as either totally impervious to an antibiotic, or totally treatable. But researchers from Emory University identified a different pattern in a certain type of drug-resistant bacteria, in which some cells in a bacterial colony are resistant to a last-resort antibiotic called colistin. This “heteroresistance” isn’t easily detectable in standard lab tests because most of the cells are susceptible to the drug.
The results of their study were published online Tuesday in the journal mBio.
Antibiotic resistance is a growing public health crisis. The Emory study’s focus, Carbapenem-resistant Klebsiella pneumoniae, is among the most common of a group of so-called “superbug” bacteria that are resistant to most antibiotics and kill up to 50% of the people they infect. More than two million people in the U.S. are sickened every year with antibiotic-resistant infections, with at least 23,000 dying, according to the Centers for Disease Control and Prevention.
Colistin is an old antibiotic which doctors administer to patients as a last resort, when the bacteria infecting them are resistant to all other antibiotics. It is often the only antibiotic that will work against these highly drug-resistant bacteria.
But the Emory study suggests that colistin may not work in some patients, even though lab tests doctors rely on to decide treatment show that it should. Carbapenem-resistant Klebsiella pneumoniae cause pneumonia, bloodstream and other infections in people with weakened immune systems, who are usually hospitalized with other conditions.
“These are really bad infections that are occurring in really sick patients,” said David Weiss, director of Emory’s Antibiotic Resistance Center, who led the research. “It’s all the more critical that you figure out what’s wrong and how to treat it.”
The scientists infected mice with the bacteria and treated them with colistin, but the mice died, according to the results published Tuesday.
This isn’t the first time scientists have identified bacterial heteroresistance to colistin. In 2016, Dr. Weiss and other Emory scientists found that a different, less common type of drug-resistant bacteria, called Enterobacter, demonstrated heteroresistance to colistin. But the bacteria in the new study are more common and worrisome.
In the new study, the bacteria the scientists gave the mice originally came from two elderly human patients at hospitals in the Atlanta area, collected as part of a surveillance program for emerging infections in Georgia that is managed at Emory. The Klebsiella bacteria were found in the blood of one patient, a transplant recipient, who died. The other patient, who had had a stroke and diabetes, had a urinary tract infection and survived. Neither patient is believed to have been treated with colistin.
“The likelihood this is a problem in humans is pretty high,” Dr. Weiss said. “There is more resistance to this last line drug than we’re aware of.”
Colistin was developed more than 60 years ago, but can cause kidney damage, so doctors stopped using it in the 1980s in favor of newer, safer medications. They have been forced to turn back to colistin in recent years, though, as bacteria have become increasingly resistant to newer drugs.
The Emory study is “really showing us that there’s a lot more resistance around than we think,” said Martin Blaser, a professor at New York University Langone Medical Center and chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, who wasn’t involved in the study. “It’s just not being picked up by regular tests.”
David van Duin, director of the Immunocompromised Host Infectious Diseases Program at the University of North Carolina, who wasn’t involved in the study, said “It’s really elegant science. This could provide an explanation for why colistin often doesn’t work in treatment.”
Dr. Weiss said this type of resistance points to a need for better diagnostic tests in clinical laboratories.
He has been studying heteroresistance since an astute microbiologist at an Emory University Hospital laboratory noticed a strange test result in 2013, and asked if he would look into it. “I thought we should explore it, and I don’t have a research lab,” said Eileen Burd, the hospital’s director of clinical microbiology.
Since then studying heteroresistance has become the priority of Dr. Weiss’s research laboratory, which is testing hundreds of bacteria samples collected in surveillance programs around the country to determine how common heteroresistance to colistin is, he said.
He also formed Emory’s Antibiotic Resistance Center, a virtual network of clinicians and basic scientists. Its research agenda is driven by findings in patients, Dr. Weiss said.
“If we’re following what’s actually happening in patients, we’re hoping that we will be led to the most relevant topics to study, “ he said. “I definitely never would have chosen to work on heteroresistance if that didn’t come through the clinic.”
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