"Antibiotic resistance is harder to control"

There are clear parallels between the spread of Covid-19 and antibiotic resistance, but the latter is more difficult to control. Interview with Patrice Nordmann.

Despite the parallels: While the Covid-19 pandemic can probably be largely halted in the foreseeable future – if a vaccine is available –, we will need to keep fighting antibiotic resistance continually for years to come. Patrice Nordmann, Head of the National Reference Center for Emerging Antibiotic Resistance (NARA), explains why.

The spread of Covid-19 is often compared to that of antibiotic resistance. What are the parallels?

The spread of both is driven by unapparent carriers, crowding, inadequate hygiene and rapid travel worldwide, and therefore a constant intermixing of the population. And they are both present in humans as well as animals, with transfer occurring between these reservoirs. In addition, the source of many important emerging resistance determinants also lies in Asia, home to half the world’s population and an increasing number of livestock. This facilitates the spread of those determinants between human and animal carriers.

Despite these parallels, the antibiotic resistance situation differs widely between countries, whereas for Covid-19 the situation has developed similarly in most countries.

Besides the parallels there are also differences. On the one hand, antibiotic resistance spreads at a slower pace. It often spreads silently at first in commensal gut bacteria. Afterwards, the antibiotic resistance genes are transferred to pathogens that cause infections, which can only be cured with difficulty or not at all with medication. In the case of Covid-19, we are dealing with a highly contagious pathogen with specific clinical signs. Therefore, a carrier of Covid-19 sitting in a plane is likely to pass the infection to other passengers. However, antibiotic-resistant bacteria travel around the world in the gut flora without anyone noticing anything and without immediately spreading to other people.

There are different types of resistance mechanisms that can be traced back to different bacterial genes. Do they all spread worldwide?

Not all, but some do. In 2003, for example, we identified a specific enzyme, one of the so-called beta-lactamases, which lead to multi-drug resistance against antibiotics in different pathogens. This enzyme was originally recovered from a bacterium isolate from Turkey, then identified in samples from different parts of the world and has become a main driver for resistances on a global scale. The same is true of other beta-lactamases, which first appeared in India and spread from there around the globe.

Does this mean that ultimately the same resistances occur everywhere?

In general, we see hotspots where certain resistance mechanisms dominate. For example, most antibiotic-resistant Enterobacterales in Switzerland are resistant due to genes that have spread first in Italy and Greece. But there are also other resistance genes around, with other origins. And new ones are constantly emerging, the situation is constantly changing.

But as you say, they spread comparatively slowly. So antibiotic resistance should be easier to contain than Covid-19?

Unfortunately, the opposite is true, for various reasons. One is that, with Covid-19, we are dealing with a sole virus. Even if we see minor mutations in the SARS-Cov-2 sequence, it’s still more or less the same virus, be it in Bern or Singapore. But in the case of antibiotic resistance, you’re faced with a wide range of unrelated resistance mechanisms which spread to different pathogens. Another important difference concerns testing. It’s difficult, by comparison, to detect antibiotic resistance because of its diversity and because only a small amount of the bacteria present in a sample is resistant. Testing for Covid-19, on the other hand, is relatively simple with PCR and antigen tests that can be performed using standard and marketed techniques.

In the current crisis there is great hope of finding a vaccine against Covid-19. Could a vaccine also be a game changer in the case of antibiotic resistance?

Once an effective and safe vaccine against Covid-19 becomes available, the solution to the pandemic will indeed be quite straightforward, similar to controlling a measles outbreak: isolating infected people and vaccinating everybody should bring the pandemic under control. Quite in contrast, the diversity of resistance determinants and the diversity of their bacterial hosts make vaccination virtually impossible. Resistance traits may be located in Enterobacterales as part of the normal human flora, making it difficult to develop vaccines against colonising bacteria.

So what other measures are needed to control the increase in antibiotic resistance?

First of all, the appropriate use of antibiotics is crucial to prevent new resistances from developing. And we need to develop rapid diagnostic techniques and identify novel bacterial targets for new antibiotics. But even this will not completely eliminate antibiotic resistance, that’s simply impossible. The best we can do is make sure we are a step ahead of the game.