Picture: Simon Davis/DFIDA woman broke her leg in India. She died in Nevada from it. Her story is the most urgent health crisis that garners the least amount of attention. Alanna Shaikh, MPH January 18, 2017 By: Alanna Shaikh, MPH on January 18, 2017 A 70-year-old woman broke her leg while visiting India. Later, she went to a hospital in Reno, Nevada. Soon after, she was dead. The cause? Something that the Director of the US Centers for Disease Control and Prevention Thomas Frieden calls a “nightmare bacteria” — a superbug that is resistant to most–if not all–existing antibiotics. This newly reported case is now shining a new spotlight on one of the most urgent threats to public health that gets the least amount of public attention: the unrelenting expansion of antibiotic resistant germs. Antibiotics are an essential tool in protecting human health. Their ability to kill bacteria and cure bacterial infections has taken diseases like syphilis, pneumonia, and tuberculosis from deadly to merely unpleasant. But now, their power is failing. Every time antibiotics are used, it gives bacteria a chance to evolve resistance to those antibiotics. And antibiotics have been used in huge quantities, for both curing human disease and adding minor productivity gains to the animal livestock industry. More and more bacteria are becoming resistant to antibiotics. In fact, seven years ago, it was predicted that we had only ten years remaining of antibiotic effectiveness. Losing antibiotics would have a staggering effect on health care. Infection after surgery would become far more common, and minor infections could easily become deadly. Minor annoyances would become risky illnesses. Gonorrhea, for example, could be deadly. Serious illnesses like pneumonia would routinely be fatal. The end of antibiotics would also do tremendous enormous economic damage. According to the World Bank, it would cause loses on par with the 2008 global economic collapse. That ten-year estimate for antibiotic effectiveness is now looking depressingly accurate. The US Centers for Disease Control and Infection (CDC) has now formally reported that an elderly woman died last September in Nevada, of a bacterial infection that was resistant to 26 antibiotics. Not one category of antibiotics. And not commonly used antibiotics. But every antibiotic formulation available in the United States. (Testing indicated that the infection might respond to an off-label intravenous use of an oral antibiotics usually used for cystitis, but the patient died before a decision could be made to acquire the intravenous drug from Europe and try it.) The patient who died had suffered a broken leg in India, and was repeatedly hospitalized in India for complications of the injury. It appears that while hospitalized she was infected with bacteria that produced a specific enzyme called New Delhi metallo-beta-lactamase 1 (NDM-1). NDM-1 makes bacteria immune to the effects of most types of antibiotics by inactivating the antibiotics on contact. It was first detected in 2008, and it has spread rapidly in the last nine years. It spreads not just from patient to patient, but from one type of bacteria to another. In other words, if the bacteria that cause pneumonia meet antibiotics resistance bacteria that cause ear infections, the ear infection bacteria can actually share their enzymes – and their resistance – with the pneumonia bacteria. This is referred to as “horizontal spread.” “Vertical spread” occurs when generations of bacteria evolve in a single patient. For example, if a tuberculosis patient does not consistently take their medication, they will kill the bacteria that are easily susceptible to antibiotics, leaving the less susceptible bacteria to take over. This will make the tuberculosis infection more difficult, or even impossible, to treat. NDM-1 does not make bacteria resistant to all antibiotics, but it is also not the only way that bacteria can become resistant. Other kinds of mutations to occur. Some bacteria lack the cell target which antibiotics attack. Some actually pump the antibiotics back out when they enter the bacteria, and others lack the entry ports that allow antibiotics into the bacteria the first place. The Nevada patient suffered an injury and subsequent infections in India. Based on her repeated hospitalizations, we can assume that the bacteria which infected her initially was resistant to some number of commonly used antibiotics. Over time, her infection grew more resistant. This was probably the result of both horizontal and vertical transmission. It’s difficult for a severely ill patient on multiple medications to take them all perfectly. Therefore, the bacteria in her body probably grew more resistant over generations. At the same time, hospitalization would have exposed her to many, many bacteria, allowing the bacteria already present in her body to acquire new forms of resistance. Eventually, she returned to the US, still sick. She was hospitalized in the US as well, and she died before anyone could try the one obscure use of antibiotics that had even a chance of saving her. Her case tells us two major things about the current state of bacterial resistance to antibiotics. This woman was not the only elderly person hospitalized in India in the last few years. If she was infected with this unkillable bacteria, so were other people. She also demonstrates the major challenge to stopping the spread of disease – people now travel, and they do so easily. She was also not the only elderly person to visit India and then come to the US. An illness in one part of the world will be an illness everywhere, soon enough. Especially something like bacterial infection that can cause minimal harm in the body until over time it grows severe enough to be fatal. The CDC and Nevada health department are putting a good face on things. While it’s a very bad sign that people are now dying of untreatable bacterial infections, infection control procedures worked. Other patients hospitalized concurrently and nearby to the patient that died were not infected with her same type of bacteria. They now recommended testing for bacterial resistance in all patients who have had medical care in India, so that resistance can be identified and patients isolated faster. There was no immediate threat to public safety. In September the United Nations General Assembly held a major summit that committed the world to taking measures to combat antibiotic resistance. They endorsed a World Health Organization blue print to take on the issue by curbing the unnecessary use of antibiotics in both animal and human health, and also spur research for the development of new antibiotics. This case in Nevada adds urgency to these global efforts, and shows the true global nature of this threat. The canaries that used to die in mines also posed no threat to public safety. Their feathered bodies were no danger to anyone. Despite all efforts to contain it, resistant bacteria are spreading, and this unlucky Nevada woman is our harbinger. If we don’t want to go back to the times when appendicitis was fatal, we need new antibacterials.