Individual antibiotic therapy – Point-of-Care monitoring of beta-lactam antibiotics in blood by coated blade spray ion mobility spectrometry

• Applicants: Dr. Thorsten Perl; Professor Dr.-Ing. Stefan Zimmermann
• Subject Area: Measurement Systems
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568359606

The increasing resistance of bacterial pathogens to antibiotics is already a major challenge for medicine. Given the limited development of new antibiotics, this situation will become even worse in the future. Current antibiotic therapy therefore concentrates on the rational and optimal use of existing antibiotics. In this context, the large group of beta-lactam antibiotics plays a central role, with therapeutic success depending primarily on sufficient antibiotic concentration at the site of infection over a period of > 60% of the therapy interval. For critically ill patients, this means frequent and individualized adjustments of dosing, which requires repeated measurements of the antibiotic concentration - therapeutic drug monitoring (TDM). Currently, TDM for beta-lactam antibiotics uses time-consuming chromatographic methods established in large laboratories. This results in a significant delay between sampling and availability of results. Thus, an increasing need for rapid point-of-care methods to closely monitor the antibiotic concentration for patient-individual adjustment of dosing exists. Ion mobility spectrometry (IMS) in combination with the coated blade spray (CBS) method is a promising approach for monitoring antibiotics and therefore in the center of this project proposal. In particular, CBS-IMS does not require time-consuming chromatographic separation, but uses solid-phase microextraction in combination with electrospray ionization (ESI). A metal blade coated with the extraction phase forms the ESI emitter, which is first simply immersed into the blood for sampling. The coated metal blade is thus used for selective extraction of antibiotics without complex sample preparation and at the same time as the ESI emitter for subsequent electrospray ionization. Most of the other components in the blood can be easily rinsed off the emitter after extraction and before ESI, so that the otherwise difficult matrix of blood is not that critical. The aim of this project is therefore the development a new point-of-care method based on CBS-IMS to significantly improve therapeutic outcome by enabling faster adaptation of antibiotic therapy to the individual needs of patients. In this context, the multivariate clinical factors influencing measurement accuracy will be investigated. Furthermore, a new algorithm for personalized dose adjustment in critically ill patients based on TDM by CBD-IMS will be developed. Finally, the CBS-IMS will be thoroughly characterized in the clinical environment with the achievable measurement uncertainty when analyzing real samples playing a central role.

• DFG Programme: Research Grants