The Most Invincible of Superbugs Heads Stateside

Gram negative bacteria, such as those reported to have colistin resistance

A report issued yesterday morning by scientists at Walter Reed Army Institute of Research revealed that a patient in Pennsylvania had been diagnosed with a urinary tract infection caused by colistin-resistant Escherichia coli. This made quite the splash for a very sobering reason: it is, for all intents and purposes, untreatable by conventional methods. Colistin is a very old antibiotic, and is only used in human medicine when everything else fails. Bacteria become colistin-resistant in one of two ways. They can mutate the target of the drug, or they can acquire a gene called mcr-1 that gives them the ability to destroy it. The second method (i.e., acquisition of mcr-1) is the more dangerous situation because a bacterial strain that has acquired it can then donate it to other organisms. Unfortunately, the Pennsylvania case is one of these.

How did this strain make its way to Pennsylvania in April? It is tempting to assume that the patient had traveled someplace far away and brought it home; however, that doesn’t seem to be the case. She has not left the state in the previous five months, suggesting that E. coli came to her rather than the other way around. In further support of this idea was an unrelated finding reported by the United States Department of Agriculture and the Centers for Disease Control and Prevention. The two Federal agencies jointly reported the isolation of colistin-resistant E. coli from the intestinal tract of a pig. This detection was part of a widespread surveillance effort to detect antibiotic resistance in farm animals, and the USDA is currently working backwards to identify which farm the infected pig was from. Nonetheless, there is no suggestion of contact between swine and the Pennsylvania patient, indicating that E. coli with an mcr-1 gene has appeared in the United States independently at least twice. Are these the only two instances? It is highly unlikely. What is likely is that colistin-resistant E. coli has been here, and we are just now detecting it.

Colistin resistance has been reported for many bacteria. Some of these (Burkholderia cepacia, Acinetobacter baumii, Stenotrophomonas maltophilia, and others) are resistant due to drug target mutations. For others (E. coli, Klebsiella pneumoniae, Salmonella spp., Pseudomonas aeruginosa, and Serratia marcesens), colistin resistance is exclusively due to mcr-1. Since we know that mcr-1 is a gene that can easily be transferred from one bacterial cell to another, and we also know that there are many pathogens that are capable of carrying and expressing mcr-1, our problems could potentially spread well beyond E. coli. In other words, we could soon see untreatable Salmonella and Klebsiella infections in the United States.

We do we do about this? There are two long-term strategies to employ. The first is to invent new antibiotics, and the second is to stop creating resistance to those we already have. Inventing new antibiotics is challenging, and will require a firm commitment from both Federal and foundation funding agencies and the pharmaceutical industry. The hard core science behind new medications where biological processes that make good drug targets are identified is often discovered at universities or research institutes who are not equipped for manufacturing, distribution, or quality control. Pharmaceutical companies have the latter capacity, but often lack the investment in “intellectual capital” to make the baseline discoveries. The stark reality is that both sectors are needed. If you feel strongly about the need for new antibiotic medications, a practical action that can be taken would be from the position of a voter or a shareholder. Do you want research invested in and prioritized? Tell your elected officials, often and loudly. Do you want good research translated into medications? Tell pharmaceutical boards, firmly and fiscally.

How do we stop creating antibiotic resistance? This is far more complex than the soundbite we’ve become accustomed to hearing involving “reckless overuse”, most notably involving the multiple ways that any given bacterial cell finds itself resistant to an antibiotic and what exactly constitutes recklessness. Two things that are important here are regulations of their use and distribution for humans and animals around the world. Antibiotics that require prescriptions in the United States are available over the counter in many countries, meaning they are used far more frequently and often inappropriately. Antibiotic use in livestock feed is a practice used worldwide, but in a fully uncoordinated way. Colistin, our “drug of last resort”, is routinely added to swine and poultry feed in China. The mcr-1 gene was first detected in China, and spread around the world from there. In other words, our nightmare scenario in the United States finds its origins in a routine agricultural practice in China. Numerous other examples such as this one exist, and clearly illustrate a coordination problem. In many ways the crisis of antibiotic resistance is reminiscent of climate change. One country’s attempts to address the issue can be unintentionally undermined by another, and it is only by fully and transparently working together that progress can be made.

This is a problem that requires global commitment to finding a solution. Humans are creative and resourceful, and I am confident we can find new ways of combating infection. Once we do, however, we need an accord across the world to treat these compounds as the precious resource that they are.

#coolistinresistance #Superbug #Ecoli