[New antimicrobial substances to combat increasing resistance].

Increasing antimicrobial resistance (AMR) is one of the greatest threats to global health. In 2021, 4.71 million deaths worldwide were closely associated with AMR, and 1.14 million deaths could be directly attributed to infections caused by multidrug-resistant organisms (MDROs), particularly multidrug-resistant Gram-negative bacteria (MDRGN). Enterobacterales (e.g., Escherichia coli and Klebsiella spp.) resistant to third-generation cephalosporins and carbapenems, multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (CRAB) have been identified by the World Health Organization as the most problematic pathogens. In addition to new diagnostic methods for the rapid identification of AMR, several new antibiotics have been approved in the last 10 years, expanding the treatment options, particularly for MDRGN infections. Pharmaceutical strategies have so far focused primarily on modifying already known classes of antibiotics with the aim of circumventing class-specific resistance mechanisms and reducing resistance rates. In addition to cefiderocol, the first siderophore cephalosporin, new combinations of β‑lactam antibiotics and β‑lactamase inhibitors (BLIs) such as ceftolozan/tazobactam, ceftazidime/avibactam, cefepime/enmetazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam, as well as the monobactam/BLI combination aztreonam/avibactam, have been approved and successfully implemented in clinical care. In addition, there is the synthetic tetracycline antibiotic eravacycline, which has a broad spectrum of activity against Gram-positive, Gram-negative (particularly clinically relevant Enterobacterales), anaerobic, and multidrug-resistant bacteria, and the new glycopeptide antibiotic dalbavancin, which is effective against Gram-positive bacteria. Since a change in legislation in 2021, the Joint Federal Committee (Gemeinsamer Bundesausschuss, G‑BA) in Germany has been authorized to classify newly approved antibiotics as reserve antibiotics. This classification allows for an exception to the regular additional benefit assessment as part of the early benefit assessment. The pipeline of antibiotics in development with novel targets and chemical structures-which had almost completely dried up-has been re-filled with new candidates for clinical trials. Some of these agents have already been tested with promising results in smaller phase 1/2 studies. In addition, monoclonal antibodies, antimicrobial peptides, small molecules, microbiome-modifying biotherapeutics, and bacteriophages, all enabling targeted and personalized treatment, are currently being investigated in studies.