How to diagnose antibiotic resistance

For targeted and efficient treatment of bacterial infections, the pathogens and their resistance patterns must be identified as quickly as possible. This is the only way to successfully treat the diseases without promoting the emergence of new antibiotic resistance. Empa researchers are working on a variety of innovative technologies that allow faster and more precise diagnostics and thus timely, customized treatment.

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The bacteria that lead to antibiotic resistance-associated deaths include Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. In 2019, they were responsible for just under one million deaths directly attributable to antibiotic resistance and around 3.6 million deaths associated with antibiotic resistance. The World Health Organization (WHO) has therefore placed bacterial pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae on the priority list for research and development. Illustration: Empa
What are the current problems in the diagnosis of antibiotic resistance?

Currently, the diagnosis of bacterial infections is usually based on growing bacteria in microbiological cultures in the laboratory, which is labor-intensive and time-consuming (1-4 days). For some bacteria, such as the slow-growing tuberculosis bacterium Mycobacterium tuberculosis, this can take even longer. This means that antibiotic treatment is usually started before the laboratory results are received and the choice of medication is therefore based on a guess. This is one of the causes of the increasing development of antibiotic resistance: As the bacteria thus come into contact with “inappropriate” antibiotics, they can subsequently develop resistance to these agents.
Researchers are therefore very interested in speeding up the diagnostic process. There are a number of approaches to automate the process. While these efforts are promising, they still rely on microbiological culture (1-2 days) to enrich the bacteria for appropriate detection.
The ideal diagnostic test should identify the specific pathogen much more quickly and indicate an appropriate therapy based on the antibiotic resistance pattern. This is particularly important for diseases such as pneumonia and blood poisoning (sepsis), which can be caused by many different pathogens (viruses, bacteria or fungi) and in which antibiotic resistance is particularly common.

What are the trends for innovative diagnostics of antibiotic resistance?

Recent innovations in bacterial diagnostics have significantly improved the speed and accuracy of identifying antibiotic-resistant pathogens. Rapid molecular diagnostics such as PCR and second-generation sequencing enable rapid and precise identification of bacterial pathogens and their resistance genes. However, it is often necessary to first enrich bacteria in clinical samples, which in turn prolongs the process.
For this reason, biosensors are currently being developed to detect bacterial infections directly, for example using antibodies and protein components that can bind to the bacteria precisely and quickly. These biosensors can be integrated into wearable devices, for example, to monitor infections in real time.
AI and specific algorithms are also increasingly being used to analyze diagnostic data. These technologies can help identify patterns in bacterial resistance and predict resistance profiles, improving diagnostic accuracy and treatment planning.

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Empa researchers are working on a variety of projects to diagnose antibiotic resistance. Image: Empa
A selection of research projects on the diagnosis of antibiotic resistance

Peptide nanosensor
Protein building blocks (peptides) that react specifically to a germ in a sample can be coupled with magnetic nanoparticles. Empa researchers are working on these peptide nanosensors to enable the specific detection and enrichment of pathogens for rapid detection. In addition, some volatile organic compounds are being investigated as sensor candidates that are also specific for certain bacteria.
Ultrafast Determination of Antimicrobial Resistant Staphylococcus aureus Specifically Captured by Functionalized Magnetic Nanoclusters
Specific capture of Pseudomonas aeruginosa for rapid detection of antimicrobial resistance in urinary tract infections
A rapid and specific antimicrobial resistance detection of Escherichia coli via magnetic nanoclusters

Biosensors
 Certain parameters in the blood or in wound exudate, so-called biomarkers, can indicate problems with wound healing and bacterial infections. Empa researchers are developing optical methods with bio-responsive materials to detect such biomarkers (e.g., pH, glucose, proteinases).
Lab-on-a-Fiber Wearable Multi-Sensor for Monitoring Wound Healing 

 

 

 

 

 

Bacterial Sensors

Empa researchers are also working on the indirect detection of specific bacteria via reaction of functionalised nanoparticles with enzymes secreted by bacteria. In one example, nanoparticles were developed that are sensitive to the enzyme urease, produced by bacteria causing pneumonia. The sensor fluoresces in the presence of this bacteria within a few hours, providing a fast, robust, sensitive, and selective detection method for Klebsiella pneumoniae and Enterobacter cloacae.
Fluorescent Probe for the pH-Independent Rapid and Sensitive Direct Detection of Urease-Producing Bacteria 


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