Effecient eradication of resistant bacteria
Many different types of bacteria have become resistant to currently available antimicrobial drugs. This research project is targeted both at research into new antibacterials and at enhancing the efficacy of existing drugs using "sensitizers." Bacteria can be divided into two main groups: Gram-positive and gram-negative bacteria. Because gram-negative bacteria are more difficult to kill due to their extra lipopolysaccharide layer and the fact that they can adapt more quickly to new antibacterials, this study is focusing on these bacteria.

We are taking a concrete look at the Pseudomonas aeruginosa bacteria, which are not unknown in hospitals and are the cause of infections in cystic fibrosis patients. First, strains (Proxy/LUMC) are tested in vitro with a large number of different antibacterials, including ampicillin (Prosensa/LUMC), during which a few hundred agents are screened as sensitizers. Then the isolated resistant strains are tested at Leiden University Medical Center, which, in turn, ultimately leads to applications related to systemic infections (LUMC) or to research into formulations for topical application (RUG).

From the in vitro research, it appears that some antibacterials which are normally used only for gram-positive bacterial infections, can have an effect in combating gram-negative Pseudomonas strains, or that active concentrations of antibacterials can be drastically reduced with the use of certain sensitizers. However, these results have not yet been confirmed in vivo. In addition, it appears that some sensitizers do not work in combinations against gram-negative bacteria but do work for gram positive types such as Staphylococcus aureus. In testing on a MRSA variant, the active concentration of the antibacterial compound could be reduced by a factor of 16. In vivo there has been too little information available to apply for a patent. Nevertheless, it has been shown that the concept of sensitizers works.

Fast facts
Full project title: Efficient eradication of resistant bacteria
Project subject: Infectious diseases
Start date: 2008
End date: 2010
Objective: Efficient eradication of resistant bacteria
PI: Peter de Visser, Prosensa
Number of investigators: 3.8 FTE
Partners: Prosensa Therapeutics BV, Proxy Laboratories BV, University of Groningen (RUG), Leiden University Medical Center (LUMC). 


Antibacterials are medications that combat infections caused by bacteria. They kill bacteria or inhibit their growth. Each type of antibacterial addresses a different group of bacteria. If antibacterials are too easily prescribed, bacteria can become insensitive (i.e. resistant) to them, and the antibacterial compound will no longer work. This means that the bacteria will survive and that patients can become very ill and might even die. In a number of countries, antibacterials are (too) widely prescribed, which results in an increasing number of resistant bacteria. 

MRSA bacteria are notorious for this. These so-called “hospital bacteria” are insensitive to nearly all normal antibacterials. Infection is especially dangerous to people with low resistance, and these bacteria form a significant danger in health care institutions. In the Netherlands, less than 1 percent of people carry MRSA because there is a limit to the use of antibacterials. In many other countries, MRSA is still an important problem. 

“TI Pharma's program managers are experts in the content, enabling them to keep parties focused on the goals that were agreed upon at the outset.”

Jan Raaijmakers
Past VP External Scientific Collaborations GSK Europe
Chair TI Pharma Board of Directors

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