Improving the efficacy of antibiotics and curbing resistance

Improving the efficacy of antibiotics and curbing resistance

antibiotic

Worldwide, more pathogens are becoming resistant to today’s antibiotics. As antibiotics lose their efficacy, infections that were once easy to treat can give rise to fatal illnesses.

The National Research Programme “Antimicrobial Resistance” (NRP 72), supported by the Swiss National Science Foundation (SNSF), is looking for ways to counteract this trend. In 45 projects, researchers have revealed new findings and developed new instruments.

“They are thus creating a basis on which we can deliver a powerful response to the threat posed by antibiotic resistance,” says Joachim Frey, President of the NRP 72 Steering Committee. “But scientific innovation doesn’t implement itself—partners from practice, industry and government are needed”.

Transmission paths of resistance revealed

Antibiotic resistance spreads between human beings, animals and the environment. Until now, it was almost impossible to trace these transmission paths. Thanks to new gene sequencing technologies, the NRP 72 researchers have discovered major interfaces, e.g. the transmission of multi-resistant pathogens from animals to veterinary clinic staff, or elevated resistance concentrations in rivers downstream from sewage treatment plants. Based on these findings, targeted action can be initiated.

So that these data can be used to rapidly detect the spread of resistance across the entire human-animal-environment biological system, researchers have developed a new portal: the Swiss Pathogen Surveillance Platform (SPSP) provides a basis on which the genetic information on bacterial pathogens can in future be linked and analyzed. The SPSP already proved its worth during the COVID-19 pandemic, when it delivered ongoing analyses of SARS-CoV-2 variants (instead of the bacterial pathogens for which it was designed).

Instruments developed for more responsible use of antibiotics

The resistance problems are worsened by the incorrect or unnecessary use of antibiotics. Therefore the researchers working on NRP 72 have developed tools and interventions to support professionals when they prescribe antibiotics. In veterinary medicine, for example, an online tool known as AntibioticScout has become established in practice. In human medicine, a number of real-world studies have demonstrated steps that can be taken to improve antibiotic prescribing.

Crucially, rapid tests are needed which enable doctors to select the correct antibiotic—or none at all. In several NRP 72 projects, researchers developed accelerated test methods, some of which are already being used in practice.

The greatest effect, however, can be achieved by prevention: where there are no infections, drugs are not needed. The aim of preventive measures against antibiotic resistance is therefore to curb the transmission of bacterial pathogens overall. In this context, a new approach to calf fattening has shown particular potential: by adopting prevention measures, the “outdoor calf” system avoids infections and reduces antibiotic use by around 80%.

New active substances found

Even if we succeed in preventing antibiotic resistance from occurring and spreading, there will still be a need to continually develop new antibiotics. In fact, there is already a high demand for new active substances right now. In NRP 72, researchers discovered a number of such substances and developed them in the laboratory.

These include both naturally occurring and synthetically manufactured substances, as well as the targeted use of components of bacterial viruses (bacteriophages) that combat pathogens. The successful projects show that academic research can systematically deliver new approaches for effective antibiotics.

Good prospects for implementation in many areas—but with a major catch

Many of these findings can be implemented in existing structures. At national level, the antibiotic resistance strategy (StAR) provides a suitable framework within which the federal government can initiate appropriate measures and coordinate the relevant key players. “But in many areas it will also need much closer involvement by other parties,” says Joachim Frey. “In both human and veterinary medicine, the cantons must be willing to provide the necessary resources for targeted programs to improve antibiotic use.”

While he is nevertheless confident in this respect, he sees much bigger hurdles that need to be overcome for the development of new medicines. Since antibiotics currently generate little or no profit, the industry partners that would be needed to develop the new substances to market-ready drugs after the research phase are not coming forward.

“This is not an issue that can be resolved through scientific findings,” says Joachim Frey. Rather—as the program summary of NRP 72 states—the government would need to act: it should create conditions in which the development of these products, which are so crucial for modern medicine, is economically viable again.

More information:
Summary of the NRP 72 Antimicrobial Resistance.

www.nfp72.ch/media/en/VGhtsJ2R … ogrammresumee-EN.pdf

H. Bürgmann et al.: NRP 72 Thematic Synthesis Routes and reservoirs of AMR-determinants & One Health AMR-surveillance.

www.nfp72.ch/media/de/MRk6j1Zn … atic-Synthesis-1.pdf

H. Naegeli et al.: NRP 72 Thematic Synthesis Optimized use of antibiotics and behavior changes.

www.nfp72.ch/media/de/f8o995tL … atic-Synthesis-3.pdf

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