Antibiotics: 6 promising avenues to fight against antibiotic resistance: Femme Actuelle Le MAG

Over the past seventy years, antibiotics have saved countless lives and enabled the development of modern medicine. These medications that destroy bacteria or prevent them from growing are essential to treat a stomach ulcer, a urinary infection or more serious illnesses such as tuberculosis and leprosy. They are also prescribed preventively and quasi-systematic before any surgical intervention. And finally, almost half of them are used by the livestock sector to care for livestock and poultry and accelerate their growth. Problem: bacteria have adapted to this over-medicalized environment by becoming less, or even more, sensitive to these drugs. As a result, more than 12,500 people die each year in France as a result of antibiotic resistance… To preserve the effectiveness of some major antibacterial molecules, developing alternative solutions is essential. Fortunately, promising avenues are emerging.

1. Monoclonal antibodies, a massive precision weapon

Manufactured in the laboratory based on the model of natural antibodies, monoclonal antibodies are among the most promising drugs. The reason: they are able to focus on a specific target and recruit the immune system so that it destroys the carrier cells of this target. In other words, they are not only directed against the pathogen, unlike traditional antibacterials. They also help the patient to better defend themselves. Monoclonal antibodies are thus used in oncologyin the fight against viruses, and “for several years, against toxins produced by bacteria”, explains pharmacist Olivier Barraud, bacteriologist at Limoges University Hospital and researcher in an Inserm laboratory. These medications make it possible, for example, to inactivate the toxins produced by the bacteria “Clostrioides difficile”, responsible for serious digestive infections. In the future, the pharmacist continues, “these antibody could be useful in infections against which we are currently powerless, or when resistance phenomena are too significant. Indeed, unlike certain classic antibiotics which often target a wide variety of bacteria and can thus multiply sources of resistance, monoclonal antibodies are very specific.. In addition, they can also be considered when a patient is already infected, to prevent them from developing a serious, or even fatal, form of the disease.

2. Agents of the immune system, against complex or local infections

Another track, antimicrobial peptides. These small molecules produced naturally by various living beings (man, animals, bacteria, etc.) play a key role in immunity because they deconstruct the protective membrane of pathogenic bacteria, thus making them permeable and vulnerable to their environment. Few have yet been developed in medicine, due to manufacturing difficulties and undesirable effects, but there are a few, mainly colistin and polymyxin B, used in aerosols or intravenously to treat complex infections resistant to other treatments. Others are in development, mainly in the form of sprays or ointments to treat local infections.

3. Viruses that devour bacteria, against bone infections

Phage therapy consists of using bacteriophages, that is to say viruses which only infect bacteria and destroy them. Discovered more than a century ago and still used in certain Eastern European countries, this method has been abandoned in favor of antibiotics, which are much easier to use. It is being considered again, particularly in France, to treat severe bone infections. “This is a very interesting avenue, because certain bacteriophages are specific to a bacterial strain, while others have a broader spectrum of action.explains Olivier Barraud. We can therefore compose personalized cocktails, depending on the type of infection.” But the constraints are important: “phages are living organisms, which multiply and evolve randomly, unlike a molecule manufactured in a laboratory which always remains the same. We must therefore improve production and purification techniques.”

4. The intestinal microbiota against certain digestive infections

We know that the microbes in our digestive microbiota defend us against bad bacteria and stimulate our immune system. Hence the idea of using fecal transplants to treat certain digestive infections recurrent infections by the bacteria “Clostrioides difficile”: a sample of the digestive microbiota of a healthy person is collected via their stools. These are then diluted in physiological serum, then the filtered preparation is transplanted into the colon of a patient. The results are excellent.

5. Strengthen the action of current drugs

Beta-lactams constitute the oldest family of antibiotics. These include penicillins (including amoxicillin) which continue to be the most prescribed today, especially against ENT infections. The problem is that more and more bacteria today produce enzymes (beta-lactamases) capable of inactivating these antibiotics. It is precisely against these enzymes that beta-lactamase inhibitors act: developed from the 1980s, they are combined with an antibiotic to block possible resistance of the targeted bacteria. The oldest and best known is clavulanic acid which, combined with amoxicillin, gives the famous Augmentin. The most recent is avibactam, marketed for less than 10 years against severe or complicated infections. “All these beta-lactamase inhibitors are interesting because they make it possible to broaden the spectrum of use of existing antibiotics, therefore in some way preserving their effectiveness.“, explains bacteriologist Olivier Barraud. Much research is underway.

6. Hope for new antibiotics

Since the discovery in 1984 of daptomycinmarketed since the beginning of the 2000s against certain serious infections of the heart, skin and soft tissues, the rare new antibiotics were most often derived from existing molecules. But, the discoveries of teixobactin (in 2015) and clovibactin (in 2023), isolated from samples taken from the soil, have awakened hope. Tested in the laboratory and on mice infected with tuberculosis, pneumococcus and Staphylococcus aureus, these drugs have proven effective. And this, without any resistance phenomenon appearing. It now remains to continue human trials.