Sana Sohail is a third-year undergraduate at the University of Chicago studying biological sciences and art.
The Rise of the Superbug
With names like “superbug”, “nightmare bacteria”, and “the phantom menace”, carbapenem-resistant Enterobacteriacaeae, abbreviated as CRE, seem to be lifted from the pages of a comic book. Making recent headlines with two confirmed cases of this superbug in the United States this past year, what exactly are CRE and what is the cause for concern? Enterobacteriaceae are a family of bacteria most frequently found in our intestines. Some of these bacteria are harmless; others are infectious pathogens that many of us are familiar with, such as E. coli, Salmonella, and Klebsiella species. Treatment for infections by these bacteria often involve antibiotics, but the CDC has issued severalwarnings about the fast-growing resistance of these microbes to commonly prescribed antibiotics like ampicillin. Antibiotic resistance is a growing problem, with scientists and medical professionals warning in the decades past that overuse of these drugs could lead to pan-resistant infections and a more vulnerable public. Concerns with these CRE superbugs are that these fears of antibiotic resistance, in an increasingly antibiotic-reliant world, have come to life. As the name gives away, carbapenem-resistant Enterobacteriaceae are resistant to carbapenems, which are last-resort antibiotics used when all other avenues of drug treatment are not working. When carbapenems are overused, bacteria that are already resistant to other drugs develop resistance to even these heavy-duty antibiotics, becoming CRE. Therefore, resistance to even these drugs leaves precious few treatment options for patients suffering from multi-drug resistant infections. CRE are sometimes also called CPE, which stands for carbapenemase-producing Enterobacteriaceae, as carbapenemase is the enzyme these bacteria have developed to destroy these antibiotics.
Naturally, the immediate question is who is at risk for these “superbug infections”? National health organizations have found that those with already weakened immune systems are at a much higher risk than the average person, as this population is more likely to be housed within a hospital, where carbapenems are most frequently used. Furthermore, immunosuppressed individuals are likely already on several types of antibiotics. Not only are their bodies less able to fight off a tenacious infection, but patients hooked up to a catheter or ventilator could have these bacteria introduced directly into their bloodstream in the event of a contamination. One such example of this scenario occurred in 2012, when a superbug was isolated at the National Institute of Health’s Clinical Center. After discovery of the bacteria, the challenge was two-fold: to treat infected patients and to thwart the spread of the infection to others. Despite the clinical center’s efforts, a study conducted after the outbreak found that the infection spread to 17 patients who were already immune-compromised, killing several of them. Doctors were forced to turn to colistin, which fortunately worked for a few patients, but the bacteria in other patients had instead become resistant to the drug.
Since then, the Washington Post reports that the NIH now “screens every patient transferring from another facility for superbugs, tests every patient in the intensive care unit twice a week and screens every patient monthly”. According to the CDC, these superbugs are a “triple threat”: not only are they resistant to nearly all antibiotics, but they also have a very high mortality rate, killing close to 50% of those with bloodstream infections. Lastly, and perhaps the greatest cause for concern, is that these superbugs “can transfer their antibiotic resistance to other bacteria”, leading to more common types of infections becoming untreatable. The Path of Least Resistance
In order to gain a better understanding of how bacteria develop resistance, take the example of one of the first confirmed cases of the superbug in the United States this year. A colistin-resistant strain of E. coliwas found in a Pennsylvania woman that, upon examination, had the gene mcr-1. It was this gene that made colistin, an old but extremelyeffective antibiotic that fell out of favour due to kidney toxicity, ineffective against the infection. The worry is that this colistin-resistance found in E. coli could spread to other bacteria, forming more types of superbugs that are resistant to last-resort antibiotics. Bacteria can become resistant via evolution, with changes to their individual genome allowing them to become resistant to antibiotics, or they can take in a plasmid that carries that resistant gene (such as mcr-1) from other bacteria.
A plasmid is a circular strand of DNA that can be passed between bacteria; the mobility of this plasmid is what has scientists and public health officials worried. A plasmid with a resistance-encoding gene can be replicated and delivered to bacteria that would otherwise respond favourably to drug treatment. This plasmid-mediated process is also known as horizontal gene transfer and could be the foremost case of drug resistance across bacteria.
As with any other infection, sanitary food preparation and hygienic practice are crucial first measures against fighting disease. The direct link between the rise of CRE superbugs and overuse of antibiotics cannot be overlooked, either: in the treatment of many diseases and sickness, caution should be taken against the administration of antibiotics when the use of other methods of treatments could be equally successful. For this reason, many hospitals across the country are adopting programs like Antibiotic Stewardship, which seek to reduce unnecessary antibiotic prescription. On the other side of things, doctors need to develop reliable ways to ensure that patients are fully complying to prescribed drug courses, because noncompliance (i.e. not finishing a course) is another major contributor to drug resistance.
On a more hopeful note, just this last week a potential saviour against these superbugs may have been found. Bacteria present in the human nose have been found to produce a hitherto undiscovered natural antibiotic, dubbed lugdunin (after the species that produces it, Staphylococcus lugdunensis). This compound has been largely successful in combating resistant strains of Staphylococcus aureus (such as the increasingly popular superbug MRSA) in mice. While this finding is preliminary and has not been tested clinically, it is indicative of a future direction of research towards not only combating (and figuring out how to contain) these nightmare bacteria, but also developing potential treatments that take advantage of natural competition between bacteria. To read more about the growing problem of antibiotic resistance, check out InfectivePerspective’s articles on the topic: Antibiotics: They’re meant for use, not abuse and The Struggling Antibiotic Pipeline.