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Clostridioides (C.) difficile ist der bedeutendste bakte¬rielle Erreger infektiöser nosokomialer Diarrhöen. Wichtigster Risikofaktor für eine Erkrankung ist die Gabe von Antibiotika, die die Darmflora schädigen – insbesondere die „4C“-Antibiotika Clindamycin, Fluorchinolone, Cephalosporine und Aminopenicilline mit Betalaktamase-Inhibitoren. Das Epidemiologische Bulletin 15/2023 gibt einen Überblick über die aktuellen Entwicklungen der C. difficile-Epidemiologie und Resistenzentwicklung in Deutschland. Veränderungen der Erregerepidemiologie und das Erkennen von neuen Erreger- und Resistenzvarianten erfordern eine kontinuierliche Surveillance, die seit 2019 standardisiert in Deutschland am Nationalen Referenzzentrum für C. difficile durchgeführt wird.

Additional file 1: Figure S1. Pocket card on the use of antibiotics with Gram-positive coverage, provided during the antimicrobial stewardship intervention on an intensive care unit in southwest Germany, 2018–2020.

Additional file 3: Table S2. Expenses for the three antibiotics studied during the investigation of an outbreak by linezolid-resistant Staphylococcus epidermidis on an intensive care unit in Germany, for 2018 and 2019 each, and the calculated differences.

In light of the global antimicrobial-resistance crisis, there is an urgent need for novel bacterial targets and antibiotics with novel modes of action. It has been shown that Pseudomonas aeruginosa elastase (LasB) and Clostridium histolyticum (Hathewaya histolytica) collagenase (ColH) play a significant role in the infection process and thereby represent promising antivirulence targets. Here, we report novel N-aryl-3-mercaptosuccinimide inhibitors that target both LasB and ColH, displaying potent activities in vitro and high selectivity for the bacterial over human metalloproteases. Additionally, the inhibitors demonstrate no signs of cytotoxicity against selected human cell lines and in a zebrafish embryo toxicity model. Furthermore, the most active ColH inhibitor shows a significant reduction of collagen degradation in an ex vivo pig-skin model. (VLID)5394757

Clostridioides difficile, a Gram-positive spore-forming bacterium, is the leading cause of nosocomial diarrhea worldwide and therefore a substantial burden to the healthcare system. During the past decade, hypervirulent PCR-ribotypes (RT) e.g., RT027 or RT176 emerged rapidly all over the world, associated with both, increased severity and mortality rates. It is thus of great importance to identify epidemic strains such as RT027 and RT176 as fast as possible. While commonly used diagnostic methods, e.g., multilocus sequence typing (MLST) or PCR-ribotyping, are time-consuming, proteotyping offers a fast, inexpensive, and reliable alternative solution. In this study, we established a MALDI-TOF-based typing scheme for C. difficile. A total of 109 ribotyped strains representative for five MLST clades were analyzed by MALDI-TOF. MLST, based on whole genome sequences, and PCR-ribotyping were used as reference methods. Isoforms of MS-detectable biomarkers, typically ribosomal proteins, were related with the deduced amino acid sequences and added to the C. difficile proteotyping scheme. In total, we were able to associate nine biomarkers with their encoding genes and include them in our proteotyping scheme. The discriminatory capacity of the C. difficile proteotyping scheme was mainly based on isoforms of L28-M (2 main isoforms), L35-M (4 main isoforms), and S20-M (2 main isoforms) giving rise to at least 16 proteotyping-derived types. In our test population, five of these 16 proteotyping-derived types were detected. These five proteotyping-derived types did not correspond exactly to the included five MLST-based C. difficile clades, nevertheless the subtyping depth of both methods was equivalent. Most importantly, proteotyping-derived clade B contained only isolates of the hypervirulent RT027 and RT176. Proteotyping is a stable and easy-to-perform intraspecies typing method and a promising alternative to currently used molecular techniques. It is possible to distinguish the group of RT027 and RT176 isolates from non-RT027/non-RT176 isolates using proteotyping, providing a valuable diagnostic tool. Open-Access-Publikationsfonds 2019 peerReviewed