The U.S. Centers for Disease Control (CDC) sounded the warning more than a year ago: COVID-19 was creating a “perfect storm” for the emergence of antibiotic-resistant infections in healthcare settings. Use skyrocketed, especially in the most critically ill patients requiring very aggressive medical interventions, but not only. The initial ignorance of the virus led, through the trial-and-error method, to the indiscriminate use of these drugs, also with less compromised patients. A study published in the Journal of Infection and Public Health in July 2020 reveals that half of those who died of SARS-CoV-2 had bacterial and fungal co-infections. Some of these organisms were drug-resistant and the problem occurred more frequently than in other patients, according to early CDC findings.
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It is estimated that antimicrobial resistance – to bacteria but also to viruses and fungi that do not respond to treatment – could have increased by around 20% in the context of the epidemic, according to Dr. María del Mar Tomás, spokesperson for the Spanish Society of Infectious Diseases and microbiologist at the hospital in A Coruña, “although more studies are still needed”. In this scenario, the Ministry of Health has taken a step forward in the surveillance of these pathogens with the creation of a specific National Surveillance System whose aim is to monitor more closely the problematic microorganisms with a homogeneous record for laboratories to diagnose how fast the problem is growing, share knowledge and design innovative treatments. Scientific studies predict a dark future if urgent action is not taken: superbugs could generate more mortality than cancer by 2050.
“This is a growing threat to public health. The rapid spread of bacteria with resistance to multiple antibiotics worldwide is especially alarming, as these bacteria limit the therapeutic alternatives against infections that generate and lead to increased morbidity and mortality,” says the document published by the Spanish Agency for Medicines and Health Products (Aemps). The text was ready in January 2020 but the pandemic has delayed the process almost two years.
700,000 deaths per year
The new system, pending inclusion in a royal decree soon, is an extension of the National Epidemiological Surveillance Network (RENAVE) – approved in 1995 – and had been working on it since the beginning of 2019, says Antonio Lopez, coordinator of the National Plan of Resistance to Antibiotics in Human Health, in conversation with elDiario.es. Now it becomes, if possible, more urgent. “There has been a brutality of very serious patients who have required more antibiotics,” says Aurora Fernández-Polo, coordinator of the group of pharmaceutical care to patients with infections (AFINF) of the Spanish Society of Hospital Pharmacy (SEFH). In addition, the COVID-19, say the experts consulted, has masked the detection of resistant bacteria “and has not had a proper identification because we were focused on the pandemic,” says Thomas.
We should not go to apocalyptic forecasts of the future because it is already a very important cause of death, four times higher than traffic accidents, and involves an extra cost of 1,500 million euros to the health system.
In the world 700,000 people die each year due to resistant microbes, 25,000 in the European Union “If extrapolated are 4,000 in Spain. We should not go to apocalyptic forecasts of the future because it is already a very important cause of death, four times higher than traffic accidents, “illustrates Lopez, which also provides the cost to the health system. Some 1,500 million euros extra. Not all the diagnosis is bad: “The pandemic has highlighted the importance of prevention, of being prepared and taking measures before there is no solution. The goal is not to reach that point and COVID-19 is a lesson,” he says.
The WHO considers the problem as one of the 10 greatest threats to humanity. They are even working on the scenario that medical advances may have to be reversed because of the risk of infection. That is to say, that very complex surgeries or treatments in the field of haematology that subject the patient to immunosuppression because of the threat of becoming infected with a resistant pathogen are being considered.
How did we get here? There are several factors, but all experts agree on one: we have abused the intake of antibiotics. Resistance occurs when bacteria mutate and become resistant to antibiotics.become immune to the antibiotics used to treat the infections they cause. The exposure to the drugs – because they are easy to take and there is no social perception that they can harm you – is so great that the surviving bacteria reproduce and become especially strong.
There’s an added issue. As they have been brutally successful, pharmaceutical companies have abandoned research into new antimicrobial treatments also because the production of these drugs “has become cheaper,” the doctors explain. “It is a natural process for bacteria to adapt, they will always try to survive. The problem is that this is accelerated,” says Fernández-Polo.
“Open science is the only way forward”.
The people researching superbugs have been collaborating for years, they know each other and ask each other for help in complex cases. That’s why scientists welcome the new system for systematically collecting data with open arms. “Everything should be accessible to everyone, like the genomes of bacteria. It is the only way to move forward, with an open science”, considers Tomás. “It is not only about having the information ourselves but also about sharing it at European and global level with homogeneous indicators to draw the pattern of evolution and from there design prevention and control measures”.
The document published by the National Plan for Antimicrobial Resistance (PRAN) currently only develops the first line: related to surveillance of certain pathogens such as gonorrhea, tuberculosis or salmonella (the latter, the main cause of gastroenteritis and diarrheal disease, is usually mild but can turn to serious in children, elderly or immunocompromised people, according to WHO).
The bacteria in the sights of microbiologists, infectologists and pharmacists are mainly three: Pseudomona aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii, according to the experts consulted. The new network requires laboratories to submit data such as whether the patient is hospitalized, their age and sex or the center of origin of the sample. It will be financed through European funds for the recovery of public health, included in the draft General State Budget, and it will involve the Ministry of Health, through the Center for Coordination of Alerts and Health Emergencies (CCAES), as coordinator of the National Network of Epidemiological Surveillance; the Institute of Public Health, the Ministry of Health, the Ministry of Health, the Ministry of Health, and the Ministry of Health, as coordinator of the National Network of Epidemiological Surveillance.d Carlos III (ISCIII); the Autonomous Communities; and the Coordinating Committee of the National Network of Laboratories for the surveillance of resistant microorganisms.
Exposure to antibiotics – because they are easy to take and there is no social perception that they can harm you – is so great that the bacteria that survive reproduce and become especially strong.
Addressing the problem cannot be understood without another leg, say the experts, which will be the next step of the new network: the development of new treatments that circumvent resistance. One of the most powerful lines of research is phage therapy, always in combination with antibiotics. “The phages resensitize the bacteria to antibiotics. If the mechanism is the pump, the phage binds and prevents the antibiotic from being expelled,” explains Tomás. “We collaborated with the Virgen Macarena and Virgen del Rocío hospitals, where a patient had persistent bacteremia for a year and a half, with fever, malaise? A treatment that we had requested from a Belgian research group was sent to him and he was injected for seven days. Then he was given antibiotics and the infection was resolved. It was a success,” says the doctor.
At the moment, the most urgent challenge is to severely reduce the prescription of antibiotics. The CDC estimates that 47 million antibiotic treatments are prescribed each year in the United States for infections that don’t need them, such as colds or the flu. “Just as we now have more experts in oncology, we need to listen more to people who specialize in infection management. An antibiotic can be prescribed by any doctor, but should be advised, with this serious situation, by more expert professionals”, concludes Fernandez-Polo, that resembles the resistance to superbugs, in the health field, with climate change.
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