Tool reveals best antibiotic combos for tough bacteria

By combining different types of antibiotics, researchers are able to treat diseases caused by multi-resistent bacteria. (Credit: Kasper Nørskov Kragh/U. Copenhagen)

A new tool speeds up the process of choosing the most effective combination of antibiotics to kill treatment-resistant bacteria.

Multi-drug-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 utilized effectively, in a targeted way, 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 have managed to find the combination in a few hours which means that they can quickly help patients with severe infections, says Niels Frimodt-Møller, head of research and chief physician at Rigshospitalet.

“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 Frimodt-Møller.

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.

“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 defense against one antibiotic can create a shortcut for the other or vice versa,” says Kasper Nørskov Kragh, an assistant professor at the University of Copenhagen who headed the study with Frimodt-Møller.

Usually, it can be both difficult and slow to find synergistic treatment combinations, as their effect on bacteria are very specific. 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 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.

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 Nørskov Kragh.

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

The study appears in the Journal of Antimicrobial Chemotherapy.

Universities and hospitals in Copenhagen, Stockholm, Rotterdam, Madrid, and Florence, as well as the Swedish company Symcel, Rigshospitalet, and the University of Copenhagen also contributed to the research.

The EU’s Horizon 2020 program funded the work.

Source: University of Copenhagen