Antimicrobial resistance (AMR) threatens global public health by rendering many antibiotics ineffective against bacterial infections. In tackling this pressing issue, it is of utmost importance to grasp the genetic foundations of antibiotic resistance. Genomic analysis provides a foundation by identifying potential resistance genes within bacterial species. However, it is the integration of transcriptomics that breathes life into our comprehension of AMR. Transcriptomics offers invaluable insights into how these resistance genes are expressed in response to antibiotic exposure. This dynamic perspective enables us to identify which specific resistance genes are actively engaged, uncover novel determinants, elucidate intricate regulatory networks, and develop tailored treatment strategies. By delving into the gene expression patterns that accompany antibiotic stress, we can not only gain a deeper understanding of resistance mechanisms but also inform the development of new antibiotics and therapies, monitor resistance evolution, and ultimately work towards more effective strategies for combatting AMR. This project focuses on investigating resistance determinants against two recently introduced antibiotics, cefiderocol and aztreonam-avibactam. Our primary research revolves around the systematic analysis of pathogens obtained from Karolinska University Hospitals, Stockholm, Sweden. Many of these pathogens exhibit enigmatic resistance mechanisms and require in-depth exploration to enhance our understanding of antibiotic resistance in clinical settings.