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AMR is the ability of microbes to defeat the medicines designed to kill them. They multiply and grow at presumably fatal concentrations of antimicrobials. It can affect parasites, fungi and viruses, but it is especially known in the field of antibiotic resistance, concerning bacteria. The consequences of AMR are that the treatment of diseases becomes difficult, and sometimes impossible, causing more severe and prolonged illness, increasing morbidity and mortality and infection relapse. This can put the success of modern medicine at risk, while also raising healthcare costs, as it increases hospitalizations and the use of complicated and sophisticated diagnostic and treatment methods.

How does AMR happen?

AMR is inherent to antimicrobial therapy and to antimicrobial compounds found in nature. AMR is a consequence of evolution through natural selection for microbial survival.

How do antibiotics fight against bacteria?

Different mechanisms are involved in the way antibiotics fight against bacteria. For example, penicillin attacks the cell wall construction, a structure that appears in the bacteria, but not in the host cells. Another mechanism is attacking the incorporation or the use of some metabolites bacteria need to be alive and grow.

How do bacteria fight against antibiotics?

In some cases, bacteria produce enzymes that destroy antibiotics. Also, bacteria can decrease the influx of antibiotics inside the bacteria. In other cases, they try to expel the antibiotics that have entered or they modify the target that antibiotics employ to kill the bacteria. Lastly, bacteria can generate new proteins with similar capacities as the antibiotic target one.

How does AMR develop?

AMR develops especially through genetics, but it sometimes develops through intrinsic bacterial mechanisms, mainly biochemicals. Also, epigenetics play a factor in AMR.

Specifically, inside a sick person, an antibiotic kills both bad and good bacteria, but the resistant bacteria stay alive. They subsequently grow and take control of the situation. This is called the Vertical Transfer of Resistance (VTR). Some bacteria transfer their resistance onto non-resistant bacteria, which is called Horizontal Transfer of Resistance (HTR).

What facilitates AMR?

The misuse and overuse of antimicrobials, in humans, but also in livestock and fish farming facilitates AMR. Furthermore, poor infection control in hospitals and clinics and a lack of hygiene and poor sanitation in living areas. Additionally, there are ecological factors, taking into account that human, animal and environmental health do not exist apart from each other, but are related to each other.

A Call to Action

As new resistance mechanisms are emerging and spreading globally and multidrug-resistant bacteria (superbugs) are increasing, new chemotherapeutics are desperately needed. Approximately 4.95 million deaths are associated with bacterial AMR in 2019 worldwide. By 2050, AMR could cause 10 million deaths a year, whereas cancer kills 8.2 million. Thus, the WHO considers AMR as one of the 10 global public health threats facing humanity and therefore, promotes a global Call to Action.

How to avoid the spread AMR?

The spread of AMR can be avoided by preventing infections, avoiding the spread of antimicrobial-resistant organisms, rational use of antimicrobials, completing antibiotic treatments, developing new antimicrobials and antibiotic adjuvants, using new treatments, faster antimicrobial susceptibility testing and AMR detection, and lastly, by the use of technology and the integration of multi-OMICS. Artificial intelligence is also a future tool to help fight AMR. Artificial intelligence can identify complex patterns in real-world data sets, paving the way for AI diagnosis of AMR and AI prediction of AMR from gene sequences. Moreover, integrating metagenomics and AI may support clinical processes and AI can facilitate the discovery of new antibiotic compounds. Despite barriers hindering the integration of AI into clinical practice, such as financial barriers, privacy and patient confidence, Mr Freire-Garabal believes the future will not stop us and eventually, AI will be part of our healthcare activity.

Manuel Freire-Garabal MD. PhD. FRSM Prof. – Professor of Pharmacology at the University of Santiago de Compostela

Written by: Christine de Zwart