From a clinical point of view, not all pathogenic bacteria are alike. We can distinguish between pathogenic bacteria, such as salmonella or shigella, which always make their carriers ill, and opportunistic bacteria, which exist in our digestive tract, skin or nasal cavities and can become infectious through a wound or a weakened immune system.
Opportunism
An example of the latter is Escherichia coli, a bacterium that lives in perfect symbiosis with our body (it is said to be commensal). This bacterial species participates in the homeostasis of the digestive tract and produces vitamins. Homeostasis is a regulatory process by which the body balances its various internal constants. But this species is also responsible for 25% of urinary tract infections. Generally sensitive to all antibiotics, this bacterium is now resistant to the standard treatment for urinary tract infections, the 3rd generation cephalosporins, in about 3% of cases1. A commensal and benign bacterium of our digestive system can thus be an infectious threat to the kidney if not treated effectively.
Unlike other diseases, these complications do not appear suddenly. You can live with antibiotic-resistant bacteria for years. They remain silent as long as the immune system and other commensal bacteria keep them in check.
During a stressful period or a viral illness, for example, the immune system can weaken and a bacterial infection can occur. The majority of the patients we care for suffer from cancer, are in intensive care or have had a transplant. Opportunistic infection situations are now more common than those caused by resistant pathogens.
The increasing prevalence of infections due to multi-antibiotic-resistant bacteria is caused by both the overuse of antibiotics and their misuse in clinical and veterinary settings. On farms, these treatments have been used not only to treat infections but also to prevent them. Since using them as a preventitive measure considerably facilitates animal growth, many farmers started using them as growth-promoters. Until 1996, pigs in France were treated preventively with glycopeptides, a class of “last-resort” antibiotics used in the treatment of staphylococci. This practice is now banned in Europe, but it continues in the United States and is contributing to the increase in bacterial resistance on a global scale.
A global and worldwide problem
The use of antibiotics in the environment is not limited to farming practices, however. A recent study has shown that medications are present in all European rivers2. Releasing active molecules into the environment encourages the selection of resistance among soil bacteria and thus their overall prevalence.
These bacteria encounter the commensal flora of the digestive tract, through unwashed hands or vegetables, and can exchange genetic material. Antibiotic treatments will then encourage the spread of resistance or its appearance. These drugs must therefore be prescribed and taken conscientiously.
Antibiotic prescitpion also needs to be considered in its social context. In India, people buy treatments according to their financial means. A rich patient will take a broad-spectrum antibiotic, i.e. one that can kill many bacteria, while a poor patient will have to make do with molecules that are effective on fewer bacteria.
In Europe, the therapeutic options are more measured. However, it is important to take into account the variations in effectiveness of an antibiotic depending on the tissue being treated. It is also essential to respect the dosage. When a patient takes an antibiotic, they often experience a rapid improvement in their symptoms, something that may lead them to stop their treatment early. But, just because the signs of infection have gone away does not mean that the bacteria have disappeared. In general, treatment not followed to the letter contributes to the development of resistance.
Imported and indigenous cases
Our laboratory has been associated with the National Reference Centre (NRC) for Carbapenem Resistant Enterobacteriaceae (CRE) for 10 years. Carbapenems are last-resort antibiotics used, in particular, in intensive care units to treat serious infections. Resistance to these molecules is a public health concern as treatment of infections is being restricted to the use of colistin. This is the last active molecule, but it has serious side effects such as irreversible damage to kidney function.
When it was created in 2012, the CNR observed carbapenem-resistant strains mainly in travellers, in particular those who had visited the Maghreb or India. People who travel to these countries have a two out of three chance of acquiring an enterobacterium resistant to one or more antibiotics. These bacteria are not necessarily pathogenic, but if the patients are temporarily immunocompromised, they can cause an infection that is difficult to treat.
Today, more than 60% of the cases we treat are indigenous, involving patients who have never travelled outside Europe and who have therefore acquired resistance in their homeland. The scale of the problem is growing and is therefore no longer limited to low-income countries.
In the city and in the hospital
Preventing the spread of these resistances is now an active battle for the medical community. Some hospitals have developed active policies that encourage the reasonable prescription of antibiotics by publishing recommendations for the use of these molecules according to the pathology in question, with the support of infectiologists for specific cases. However, there is still room for improvement. France is the third largest consumer of antibiotics in Europe. The development of rapid tests to distinguish between viral and bacterial infections, particularly for sore throats, is a lever for reducing their misuse in our country and elsewhere. The aim is to guarantee the effectiveness of available antibiotics for as long as possible. Research and development of new therapeutic solutions will not be enough to curb the crisis. Very roughly speaking, the pharmaceutical industry needs 20 years to develop a new antibiotic, whereas it only takes 24 hours for a bacterium cultivated in the laboratory to become resistant. Proper use, in the right doses and for the right reasons, will allow us to safeguard these precious molecules while waiting for new therapies, such as phagotherapy, immunotherapy, or antimicrobial peptides, and of course new, more effective antibiotics.
