He is building bridges to combat antibiotic resistance

In Thomas Tängdén’s laboratory at Hubben in Uppsala, it is important not to touch benches, chairs or other objects. And when we leave, we have to sanitise our hands and disinfect the soles of our shoes as a safety measure. Here, research is being conducted on multidrug-resistant bacteria, some of which are resistant to all available antibiotics.

“We are investigating why they are resistant and how we can prevent them from becoming even more resistant. Above all, we are trying to find treatments that are effective. We work a lot with combination therapy, where we administer two or three antibiotics at the same time to see whether they have synergistic effects,” explains Thomas Tängdén.

Research began after major hospital outbreak

Thomas Tängdén has been researching antibiotic resistance for more than 15 years and is involved in writing treatment guidelines for how bacterial infections should be managed, both in Sweden and in Europe as a whole.

“I started researching in connection with a major hospital outbreak of resistant bacteria at Uppsala University Hospital in 2005–2008. Effective treatment was still available for the bacteria that caused the outbreak, ESBL-producing Klebsiella pneumoniae. But since then, the bacteria have become more resistant, and we are now seeing increasing resistance to last-line antibiotics – carbapenems,” explains Thomas Tängdén.

Resistance develops rapidly, and certain bacteria are masters at mutating to adapt to new living conditions.

“A number of new antibiotics have been introduced in recent years that are supposed to work against carbapenem-resistant bacteria. In clinical studies, we have collected bacteria on repeated occasions to see if they develop resistance to the new preparations during ongoing treatment. Unfortunately, this happens in up to one tenth of patients within a week,” says Thomas Tängdén.

Intestinal bacteria from our normal flora

Many of the most difficult-to-treat bacteria are intestinal bacteria found in our normal flora, the microbiota. The intestinal flora is important for our health and is affected by a course of antibiotics. Through DNA analysis, Thomas Tängdén’s research team has discovered that its composition may be altered for a long time after the patient stops taking the medicine, without the patient even noticing this.

“The effects on the microbiota vary greatly between different antibiotics. Some antibiotics have hardly any effect at all, while others cause dramatic changes in the composition of the intestinal flora within a few days, which can persist for over a year. It is important to develop this type of knowledge as support in making treatment decisions and when writing new treatment guidelines. If two antibiotics are roughly equally effective in treating an infection, we choose the one that has the least negative effect on the intestinal flora and contributes least to the development of resistance,” he says.

Need for broad-based collaboration

Antibiotic resistance is a global and growing problem, and large-scale, broad-based collaboration is needed to solve it. Thomas Tängdén devotes much of his time to precisely that. Among other things, he is project manager for the major national initiative Platinea, a collaboration between 22 partners from several sectors, including the research community, healthcare, government authorities and companies. One focus of the project is to make existing antibiotics more accessible to healthcare providers. Something they have already noticed is weaknesses in the supply chains, which often lead to shortages of important medicines.

Another project led by Thomas Tängdén is the international collaboration INTRODUCE, which focuses on responsible use of new antibiotics that come out so they can reach patients who need them while avoiding overuse, which drives the development of resistance.

“It is important to invest more resources in developing new antibiotics, but we must also ensure that the few new preparations that are approved are not released onto the market without any control. A system is needed to manage new antibiotics, and that is what this project is about,” says Thomas Tängdén.

Working with the WHO

He also works directly with the World Health Organization (WHO) to help steer antibiotic development towards existing medical needs. He has led the work of identifying which types of antibiotics most urgently need to be developed, which bacteria they should be effective against, and what types of infections and patients they should be used for.

“The WHO project is a way of drawing attention to areas that are overlooked when it comes to antibiotic development. It has been interesting and important to talk to experts from all over the world within the project, as we live in very different realities in terms of both resistance and healthcare resources,” explains Thomas Tängdén.

Despite the progress being made, he is not very optimistic that the problems with antibiotic resistance are anywhere near being solved.

“It doesn’t look good and will certainly get worse before it gets better. There are positive initiatives and increased awareness at the political level. But far too little is currently being done in practice, and I don’t think many people understand how serious the consequences of antibiotic resistance could be for large parts of modern healthcare.”

Threat to medical development

The picture he paints of a world where medicines are no longer effective against bacteria is a dark one.

“If we don’t reverse this trend, the lack of effective antibiotics will threaten treatments that we take for granted today. Patients with cancer or blood disorders that require stem cell transplants are completely dependent on effective antibiotics. Intensive care and major surgical procedures may become too risky if there are no antibiotics available to prevent or treat infections. If the resistance problem becomes too big, it will threaten all medical development and have consequences for society as a whole. We still have a way to go, but I think more people need to take this on board to understand the enormous investments that are needed,” says Thomas Tängdén.

Åsa Malmberg