A Multipronged Attack Can Halt Multi-Resistant Bacteria in Their Tracks

Infectious diseases caused by bacteria may be treated with antibiotics. But sometimes, the bacterium becomes resistant to the treatment which results in a long and complicated course of disease. Recent studies have shown that combining several types of antibiotics can effectively prevent resistance.

Multi-resistant bacteria are a major global problem. The number of new resistant bacteria is constantly increasing, and there are no new types of antibiotics on the way for the patients in the foreseeable future. Therefore, existing antibiotics must be utilised effectively, targeted and without increasing consumption.

Previous studies have shown that a combination of different types of antibiotics can be effective in connection with some multi-resistant bacteria. But so far, the problem has been that it may take several days to find the right combination, and this may have serious consequences for patients with complicated courses of disease.

Now, researchers from Rigshospitalet and the University of Copenhagen have managed to find the combination in a few hours which means that they can quickly help patients with severe infections, says Head of Research and Chief Physician at Rigshospitalet, Niels Frimodt-Møller.

‘The result paves the way for the ability to provide guidance on the treatment of serious infections on the very day when we find the bacterium which is the cause of, for example, blood poisoning; nowadays, it usually takes several days to find a relevant treatment, especially if it is resistant to most antibiotics, and rapid treatment of, for example, blood poisoning is crucial in order to save the patient's life’, says Niels Frimodt-Møller.

The study, which has just been published in the acclaimed British journal, Journal of Antimicrobial Chemotherapy, is a collaboration between universities and hospitals in Copenhagen, Stockholm, Rotterdam, Madrid and Florence as well as the Swedish company Symcel. The project is funded through EU's Horizon 2020 programme.

New technology finds combinations quickly

By using a completely new technology to screen clinical multi-resistant bacterial strains, the researchers have found several combinations of antibiotics which have provided a significantly more effective treatment of the bacteria. Assistant Professor Kasper Nørskov Kragh from the University of Copenhagen, who has headed the study together with Niels Frimodt-Møller, says:

‘A bacterium that is resistant to antibiotics A or antibiotics B when used on their own may in some cases be very responsive when A and B are used at the same time. This may be due to the fact that the bacterium's defence against one antibiotic can create a shortcut for the other or vice versa’, says Kasper Nørskov Kragh.

Usually, it can be both difficult and slow to find synergistic treatment combinations, as they are very specific in their effect on bacteria. For example, a combination therapy may be effective on one bacterium, but not on the next. In their study, the researchers have solved this issue as well.

‘Using a new microcalorimetry technique that can detect heat generation from very small amounts of live bacteria, we were able to screen a large number of combinations of different types of antibiotics and within a few hours find candidates for the specific bacterial strain from the individual patient. Subsequently, we have tested the combinations that have been shown to have a synergistic effect on the individual bacterial strains in a thorough mouse experiment’, says Kasper Nørskov Kragh.

The researchers have also been able to demonstrate that the combinations that worked with the screening technique did indeed have a much better effect in the animal model as well.

Personalised medicine

As the study uses well-known and approved drugs in a new and effective way, the researchers hope that the finding may benefit patients within a relatively short time horizon.

‘It may be a new and effective tool for the diagnostic departments to plan the optimal treatment of the individual patient’, says Kasper Nørskov Kragh.

The results open up the possibility of using the technique in the diagnosis of severe multi-resistant infections, says Chief Physician Niels Frimodt-Møller.

‘With this screening method, doctors can get an indication as to which combinations of antibiotics can help the individual patient within a relatively short time – hours. It provides an opportunity to use our entire current arsenal of antibiotics in a new way that can help patients now and here’, says Niels Frimodt-Møller.

Reference
Kragh KN, Gijón D, Maruri A, et al. Effective antimicrobial combination in vivo treatment predicted with microcalorimetry screening. Journal of Antimicrobial Chemotherapy. 2021;(dkaa543). doi:10.1093/jac/dkaa543

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