New Superbug Resists Last-Line Antibiotic Colistin

This colistin-resistant superbug was found in the United States

antibiotic testing
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During his administration, President Obama has received a lot of flak for issuing executive orders. An executive order allows the president to set policy without the input of Congress and benefit of public debate.

Whereas some of Obama’s executive orders have resulted in partisan controversy and bickering, the benefit of others are widely appreciated. Specifically in 2015, Obama issued The National Action Plan for Combating Antibiotic-Resistant Bacteria.

According to the Obama administration, here are the goals of this executive order:

  1. Slow the Emergence of Resistant Bacteria and Prevent the Spread of Resistant Infections.
  2. Strengthen National One-Health Surveillance Efforts to Combat Resistance.
  3. Advance Development and Use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria.
  4. Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines.
  5. Improve International Collaboration and Capacities for Antibiotic-resistance Prevention, Surveillance, Control, and Antibiotic Research and Development.

To meet these goals, the president enlisted the aid of various organizations, including the Department of Defense (DoD), Department of Agriculture (USDA), and Department of Health and Human Services (HHS). In May 2016, these agencies released news: colistin-resistant mcr-1 E. coli was discovered in a patient at Walter Reed Medical Center in the United States.

This patient had a urinary tract infection that was fortunately able to be treated with another antibiotic.

Colistin is a last-line drug in our defense against disease. Many public health experts, researchers, and clinicians alike have feared colisitin resistance for some time. Furthermore, the mcr-1 E. Coli has the ability to transfer this antibiotic resistance to other bacteria using plasmids.

Why Worry About Antibiotic Resistance?

Ever since 1928, with the introduction of penicillin, antibiotics have saved several million lives worldwide. Shortly after the introduction of antibiotics, resistance among certain strains of bacteria was observed. In recent years, this resistance has increased and multidrug-resistant bacteria, or superbugs, have become a serious threat to public health and safety.

The CDC estimates that nearly two million drug-resistant infections occur each year in the United States resulting in an estimated 23,000 deaths.

With the recent explosion in multidrug resistance, the number of treatments that do work against such bacteria has dwindled. Furthermore, antibiotics that do treat resistant organisms can be pretty expensive.

What Is Colistin?

Colistin belongs to a class of antibiotics known as polymyxins. Two types of polymyxins exist: polymyxin B and polymyxin E. Colistin is polymyxin E and the most widely used of the two.

Colistin was first used in the 1960s; however, use of this agent was quickly stopped because it resulted in substantial neurotoxicity and nephrotoxicity.

In other words, colistin caused nerve and kidney damage, respectively.

In recent years with the rise of multidrug resistance, we’ve had to reintroduce colistin to combat bacteria that now resists more conventional antibiotics. Colistin is remarkably effective but works on relatively few bacterial pathogens, such as P aeruginosa, Acinetobacter species, and Klebsiella species. Of note, all these different types of bacteria can result in infections of the blood (sepsis) and infections of the lung (pneumonia), urinary tract infections, skin and wound infections, as well as infections after surgery. Additionally, these bacteria typically infect people who are very sick and have compromised immune systems.

Transfer of Antibiotic Resistance by Plasmids

What makes this new colistin-resistant strain of E. Coli troublesome is that it can transfer genetic information coding for resistance to other bacteria via plasmids (ie, mcr-1 or plasmid-mediated polymyxin resistance mechanism).

As reported in The Lancet in November 2015, Chinese researchers were the first to discover this new superbug. The researchers found this resistant bacteria during a routine surveillance project examining antimicrobial resistance among commensal Escherichia coli obtained from animals in the food supply.

In the interim between the Chinese discovery of this bacteria and this bacteria popping at Walter Reed National Military Center, where federal researchers identified it, this superbug has been identified in several other countries, too, which means it has already spread globally.

Fortunately, follow-up investigation by the National Antimicrobial Resistance Monitoring System—a coordinated effort between the USDA, Health and Human Services (HHS), and various state and local health department—is showing that isolates of colistin-resistant E. coli are rare. Furthermore, isolates  from Salmonella and Klebsiella, other types of bacteria, didn’t demonstrate evidence of the mcr-1 gene.

The transfer of genetic information between bacteria is pretty fluid. Not only can bacteria transfer information coding for resistance to offspring—referred to as vertical transmission—but bacteria can also transfer such information by means of horizontal gene transfer. In other words, even after a bacterium is formed it can pick up genetic information from another bacterium.

More specifically, this process of horizontal gene transfer is mediated by plasmids, or free-floating bits of small, circular, double-stranded DNA, which are separate from a cell’s chromosomal DNA. Plasmids contain information that proffer genetic advantages to bacteria, such as antibiotic resistance. With horizontal gene transfer, plasmids are transferred among bacteria.

Let's put horizontal gene transfer of antibiotic resistance genes in perspective by means of an (albeit a bit silly) analogy. Imagine you were at a party and another person had some magical ability to resist cyanide. This magical ability was encoded in her genes and could be passed down to her children. Additionally, this ability could be transferred to another person by simply taking a sip of her cocktail. Before you know it, everybody is taking a sip out her drink. Furthermore, other revelers at the party have their own magical resistances to poison, which they in turn share with others by means of their own booze. Before you know it, certain partygoers have stockpiled a bunch of resistances that help them combat a variety of poisons.

Conclusion

The existential threat that transferable colistin resistance poses may feel disquieting. As an individual, you can do your part to limit antibiotic resistance by taking antibiotics only when you need to. You should also make sure to complete your entire course of antibiotics, since premature cessation promotes growth of drug-resistant strains. Finally, because mcr-1 E. Coli and other bacteria can be found in meat and poultry products, it’s always a good idea to fully cook your food before consumption.

Sources:

Bhalodi A, Nicolau DP. Principles of Antimicrobial Therapy and the Clinical Pharmacology of Antimicrobial Drugs. In: Hall JB, Schmidt GA, Kress JP. eds. Principles of Critical Care, 4e. New York, NY: McGraw-Hill; 2015. Accessed May 29, 2016.

Carroll KC, Hobden JA, Miller S, Morse SA, Mietzner TA, Detrick B, Mitchell TG, McKerrow JH, Sakanari JA. Microbial Genetics. In: Carroll KC, Hobden JA, Miller S, Morse SA, Mietzner TA, Detrick B, Mitchell TG, McKerrow JH, Sakanari JA. eds. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 27e. New York, NY: McGraw-Hill; 2015. Accessed May 29, 2016.

Liu, Yi-Yun et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. The Lancet Infectious Diseases, Volume 16, Issue 2, 161 - 168.

Ram S, Rice PA. Chapter 144. Gonococcal Infections. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. Accessed October 25, 2014. 

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