The era of antibiotics is over. And now what?

When Alexander Fleming returned from vacation in the summer of 1928, and found in his London laboratory a table contaminated with the mold Penicillium notatum, he began a new era of the superiority of science over nature. Since then, antibiotics, both open to him personally and many others discovered through his work, have saved millions of lives and saved a huge number of people from suffering. But from the very beginning of this era, scientists knew that it would come to an end. They simply did not know exactly when.



The resistance of bacteria to antibiotics is natural and inevitable. By chance, several bacteria will have genes that can protect them from drugs; they will pass these genes on - and not only to their offspring, but sometimes to their neighbors . Computational epidemiology specialists finally get the necessary data and process it to simulate this phenomenon. But no one is trying to use these tools to predict the end of the era of antibiotics - it has already come. They concentrate on understanding how soon resistant bacteria will end up in the majority and what doctors can do with them - if at all possible.



In 2013, the then director of the Centers for Disease Control and Prevention (CDC) Tom Frieden told reporters : “If we don’t behave cautiously, we will soon find ourselves in a post-antibiotic era.” Today, just four years later, this agency claims that we are in it. “We say this because a universally resistant bacterium has appeared,” says Jean Patel, who heads the CDC's antibiotic strategy and coordination. "People are dying because there are no antibiotics that can cure their infections — infections that were not so long ago easily cured."



Last August, a woman over 70 fell to a hospital in Reno, pc. Nevada, with bacterial infection of the thigh . The bacterium belonged to a class of particularly resistant microbes, known as carbapenem-resistant enterobacteria (CRE). But this bacterium was not taken either by carbapenems , or tetracycline , or colistin , and in general no antibacterial device out of 26 commercially available. A few weeks later she died of septic shock.



For public health officials, to whom Patel belongs, this case marks the end of an era and the beginning of a new one. The question is: how quickly can this universal resilience spread? “When we get to a situation in which the infection will often be impossible to cure than is possible? - says Patel. “It will be very difficult to predict.”



She knows this for sure because she has already tried. In 2002, the first vancomycin-resistant staphylococcus manifested itself in a 40-year-old Michigan man with chronic leg ulcers. The situation seemed very sad: staphylococcus is one of the most common infections in people, and vancomycin is the most common antibiotic for its treatment. In addition, the resistive gene was located on a plasmid , a freely moving DNA ring, which allowed it to move easily. CDC epidemiologists have worked with microbiologists, such as Patel, to create a model that predicts how far and how quickly it can spread. Patel does not remember the exact numbers, but she recalls that the results were frightening. “We are very concerned about this issue,” she says.



Fortunately, in this case the models were wrong. Since 2002, only 13 cases of vancomycin resistant staphylococcus have been reported, and all patients survived.



Such a mistake is very puzzled team. But in biology sometimes there are such difficulties. “I worked with this bacterium in laboratories, where it grows beautifully, but from person to person, apparently, does not apply,” says Patel. And although they still do not know why, one of the hypotheses suggests that the appearance of this resistant gene does not pass completely for the bacteria. He made staphylococcus impervious to his sworn enemy, at the same time complicating the process of survival outside the human body. Hospital rules, time of year, geography can also affect distribution. This is like trying to predict the weather.



“It’s not possible to make such predictions on paper or by scrutiny,” said Bruce Lee, a public health researcher at the John Hopkins Institute. He works with healthcare organizations in Chicago and Orange County, predicting the most likely pathways for CRE, the bacteria of the type that killed a woman in Nevada, if they appear in hospitals. In the past, such models were based solely on mathematics — this is how Patel tried to build her predictions. Yes, their equations were complex, but not enough to take into account such things as human behavior, the biology of bacteria and their interaction with the environment. "In our area, people are increasingly beginning to understand that in order to deal with the spread of antibiotic-resistant bacteria in a sufficient degree of detail, it is necessary to work with models based on data in which you can view millions of different scenarios - just like meteorologists do." Says Lee.



In a study published last year by Lee, he describes the likelihood of CRE spreading in 28 hospitals and 74 Orange County nursing homes. In this model, each virtual hospital was assigned the number of beds that match the number of beds in real institutions, as well as all the information about the connectivity of institutions. In the model, each patient was a computational unit that either transfers or does not transfer CRE on any given day. These units moved along the health care ecosystem, interacted with doctors, nurses, cots, chairs, and doors a hundred million times, and with each new simulation these parameters were slightly adjusted. He found that without strengthening measures to control, for example, regular patient testing for vector resistance and quarantine, CRE would become endemic — ever present — in almost all Orange County hospitals in ten years.



And after CRE penetrates the health care system, it will be difficult to get rid of it. “It's like trying to drive termites out of the house,” says Lee. “As soon as they make their way to where everything is connected with everything, they become an intractable part of the ecosystem.” So, if doctors and sisters can quickly identify people who can spread CRE, they can at least isolate the threat. Even if they cannot offer anything to the patients themselves.



So far, the good news is that the only cases of human-to-human transmission of 100% resistant bacteria occur only in Lee's supercomputer. In the real world, such cases are not recorded. But it is their search for Patel and the CDC. This will bring the situation to the next level, says Patel. To keep abreast, last year, the agency spent $ 14.4 million to build a network of seven local laboratories capable of conducting genetic testing of bacterial samples taken from hospitals. Now they are implementing a program that someday will be able to link all hospitals in the United States with the CDC tracking system directly to automatically mark every event that occurred in the United States associated with antibiotic-resistant bacteria in real time.



In parallel, Patel, and, with varying success, the rest of the world, oversees the development of antibiotics. In this area, too, everything is not smooth. Last week, the World Health Organization released a report analyzing all of the antibacterial drugs in development. The conclusions are grim: not enough medicine, not enough innovation. For each new medicine out of 51 variants, it is already possible to find microorganisms resistant to it in advance. Researchers, such as Patel and Lee, hope that their work will help minimize existing threats, discover new ones as they appear, and give pharmacological companies time to develop new drugs. The era of antibiotics may have ended - but with the upcoming new era, much can still be done.