Therapierelevante Antibiotikaresistenzen im One-Health-Kontext

„One Health“ bezeichnet ein Konzept, das die Gesundheit von Menschen, Tieren und der Umwelt miteinander verbindet. In Deutschland gibt es umfangreiche Daten zur Antibiotikaresistenz (AMR) und multiresistenten Erregern (MRE) in der Human- und Veterinärmedizin sowie aus Untersuchungen in verschiedenen Umweltkompartimenten (Boden, Wasser, Abwasser). Die Erhebung erfolgt nach unterschiedlichen Vorgaben und Standards, was den Vergleich von Daten erschwert. Ein Fokus auf humantherapeutisch wichtige AMR und MRE ist hilfreich, um eine gewisse Orientierung vorzugeben. Die meisten Daten liegen sektorübergreifend zu Methicillin-resistenten Staphylococcus aureus und multiresistenten Enterobacterales wie Escherichia coli und Klebsiella pneumoniae vor. Hier sind die Trends der Resistenzen heterogen. Der Einsatz von Antibiotika führt zur Selektion von MRE, was gut dokumentiert ist. Erfolge bei der Minimierung des Antibiotikaeinsatzes konnten in zurückliegenden Jahren für einzelne Sektoren dargestellt und z. T. mit Erfolgen in der Eindämmung von AMR und MRE korreliert werden (Rückgang MRSA in der Humanmedizin). Auch sektorspezifische Maßnahmen zur Senkung der Last durch MRE und AMR sind notwendig, da Resistenzprobleme nicht generell eine Verknüpfung mit anderen Sektoren aufweisen. Carbapenemresistenzen sind vor allem bei pathogenen Erregern vom Menschen nachweisbar. Colistinresistenzen kommen in verschiedenen Sektoren vor, zeigen aber dort jeweils verschiedene Mechanismen. Resistenzen gegen Reservesubstanzen wie Linezolid sind in Deutschland selten, sie zeigen aber einen konkreten One-Health-Bezug. Bestrebungen zur Harmonisierung von Methoden, z. B. im Bereich der antimikrobiellen Empfindlichkeitstestung und genombasierten Erreger- und AMR-Surveillance, sind ein wichtiger erster Schritt zu einer Vergleichbarkeit der verschiedenen Datenerhebungen.One Health refers to a concept that links human, animal, and environmental health. In Germany, there is extensive data on antibiotic resistance (AMR) and multidrug-resistant (micro)organisms (MDRO) in human and veterinary medicine, as well as from studies in various environmental compartments (soil, water, wastewater). All these activities are conducted according to different specifications and standards, which makes it difficult to compare data. A focus on AMR and MDRO of human therapeutic importance is helpful to provide some guidance. Most data are available across sectors on methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Enterobacterales such as Escherichia coli and Klebsiella pneumoniae. Here, the trends of resistance are heterogeneous. Antibiotic use leads to MRE selection, which is well documented. Success in minimizing antibiotic use has also been demonstrated in recent years in several sectors and could be correlated with success in containing AMR and MDRO (e.g., decrease in MRSA in human medicine). Sector-specific measures to reduce the burden of MDRO and AMR are also necessary, as not all resistance problems are linked to other sectors. Carbapenem resistance is still rare, but most apparent in human pathogens. Colistin resistance occurs in different sectors but shows different mechanisms in each. Resistance to antibiotics of last resort such as linezolid is rare in Germany, but shows a specific One Health correlation. Efforts to harmonize methods, for example in the field of antimicrobial susceptibility testing and genome-based pathogen and AMR surveillance, are an important first step towards a better comparability of the different data collections.Peer Reviewe

Case Study: Using a Shared International Database to Document Veterinary Consumption of Antibiotics in Pakistan

In this paper, we present a case study of Pakistan documenting the use of antimicrobial drugs in poultry flocks in the VetCAb-ID database. Unlike other databases, this system allows international users to upload their data directly. Based on expert interviews and a review of the latest publications on the topic, we provide an alternative approach to harmonizing data collection among countries. This paper will provide impetus to formulate joint requirement documentation for an AMU database on a global level that international users can adapt for their own purposes and projects

Formation of Neutrophil Extracellular Traps by Reduction of Cellular Cholesterol Is Independent of Oxygen and HIF-1α

Formation of neutrophil extracellular traps (NETs) is a two-faced innate host defense mechanism, which, on the one hand, can counteract microbial infections, but on the other hand, can contribute to massive detrimental effects on the host. Cholesterol depletion from the cellular membrane by Methyl-β-cyclodextrin (MβCD) is known as one of the processes initiating NET formation. Since neutrophils mainly act in an inflammatory environment with decreased, so-called hypoxic, oxygen conditions, we aimed to study the effect of oxygen and the oxygen stress regulator hypoxia-inducible factor (HIF)-1α on cholesterol-dependent NET formation. Thus, murine bone marrow-derived neutrophils from wild-type and HIF-knockout mice or human neutrophils were stimulated with MβCD under normoxic (21% O2) compared to hypoxic (1% O2) conditions, and the formation of NETs were studied by immunofluorescence microscopy. We found significantly induced NET formation after treatment with MβCD in murine neutrophils derived from wild-type as well as HIF-1α KO mice at both hypoxic (1% O2) as well as normoxic (21% O2) conditions. Similar observations were made in freshly isolated human neutrophils after stimulation with MβCD or statins, which block the HMG-CoA reductase as the key enzyme in the cholesterol metabolism. HPLC was used to confirm the reduction of cholesterol in treated neutrophils. In summary, we were able to show that NET formation via MβCD or statin-treatment is oxygen and HIF-1α independent

The upper respiratory tract of felids is highly susceptible to sars‐cov‐2 infection

Natural or experimental infection of domestic cats and virus transmission from humans to captive predatory cats suggest that felids are highly susceptible to SARS‐CoV‐2 infection. However, it is unclear which cells and compartments of the respiratory tract are infected. To address this question, primary cell cultures derived from the nose, trachea, and lungs of cat and lion were inoculated with SARS‐CoV‐2. Strong viral replication was observed for nasal mucosa explants and tracheal air–liquid interface cultures, whereas replication in lung slices was less efficient. Infection was mainly restricted to epithelial cells and did not cause major pathological changes. Detection of high ACE2 levels in the nose and trachea but not lung further suggests that susceptibility of feline tissues to SARS‐CoV‐2 correlates with ACE2 expression. Collectively, this study demonstrates that SARS‐ CoV‐2 can efficiently replicate in the feline upper respiratory tract ex vivo and thus highlights the risk of SARS‐CoV‐2 spillover from humans to felids

Phylogeny and spatiotemporal dynamics of hepatitis E virus infections in wild boar and deer from six areas of Germany during 2013–2017

The hepatitis E virus (HEV) can cause acute and chronic hepatitis in humans. Infections with the zoonotic HEV genotype 3, which can be transmitted from infected wild boar and deer to humans, are increasingly detected in Europe. To investigate the spatiotemporal HEV infection dynamics in wild animal populations, a study involving 3572 samples of wild boar and three deer species from six different geographic areas in Germany over a 4-year period was conducted. The HEV-specific antibody detection rates increased between 2013-2014 and 2016-2017 in wild boar from 9.5% to 22.8%, and decreased in deer from 1.1% to 0.2%. At the same time, HEV-RNA detection rates increased in wild boar from 2.8% to 13.3% and in deer from 0.7% to 4.2%. Marked differences were recorded between the investigated areas, with constantly high detection rates in one area and new HEV introductions followed by increasing detection rates in others. Molecular typing identified HEV subtypes 3c, 3f, 3i and a putative new subtype related to Italian wild boar strains. In areas, where sufficient numbers of positive samples were available for further analysis, a specific subtype dominated over the whole observation period. Phylogenetic analysis confirmed the close relationship between strains from the same area and identified closely related human strains from Germany. The results suggest that the HEV infection dynamics in wild animals is dependent on the particular geographical area where area-specific dominant strains circulate over a long period. The virus can spread from wild boar, which represent the main wild animal reservoir, to deer, and generally from wild animals to humans

Structure–activity study of the antibacterial peptide fallaxin

Fallaxin is a 25-mer antibacterial peptide amide, which was recently isolated from the West Indian mountain chicken frog Leptodactylus fallax. Fallaxin has been shown to inhibit the growth of several Gram-negative bacteria including Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Here, we report a structure–activity study of fallaxin based on 65 analogs, including a complete alanine scan and a full set of N- and C-terminal truncated analogs. The fallaxin analogs were tested for hemolytic activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant S. aureus, (VISA), methicillin-susceptible S. aureus (MSSA), E. coli, K. pneumoniae, and P. aeruginosa. We identified several analogs, which showed improved antibacterial activity compared to fallaxin. Our best candidate was FA12, which displayed MIC values of 3.12, 25, 25, and 50 μM against E. coli, K. pneumoniae, MSSA, and VISA, respectively. Furthermore, we correlated the antibacterial activity with various structural parameters such as charge, hydrophobicity 〈H〉, mean hydrophobic moment 〈μH〉, and α-helicity. We were able to group the active and inactive analogs according to mean hydrophobicity 〈H〉 and mean hydrophobic moment 〈μH〉. Far-UV CD-spectroscopy experiments on fallaxin and several analogs in buffer, in TFE, and in membrane mimetic environments (small unilamellar vesicles) indicated that a coiled-coil conformation could be an important structural trait for antibacterial activity. This study provides data that support fallaxin analogs as promising lead structures in the development of new antibacterial agents

Therapy-relevant antibiotic resistances in a One Health context

„One Health“ bezeichnet ein Konzept, das die Gesundheit von Menschen, Tieren und der Umwelt miteinander verbindet. In Deutschland gibt es umfangreiche Daten zur Antibiotikaresistenz (AMR) und multiresistenten Erregern (MRE) in der Human- und Veterinärmedizin sowie aus Untersuchungen in verschiedenen Umweltkompartimenten (Boden, Wasser, Abwasser). Die Erhebung erfolgt nach unterschiedlichen Vorgaben und Standards, was den Vergleich von Daten erschwert. Ein Fokus auf humantherapeutisch wichtige AMR und MRE ist hilfreich, um eine gewisse Orientierung vorzugeben. Die meisten Daten liegen sektorübergreifend zu Methicillin-resistenten Staphylococcus aureus und multiresistenten Enterobacterales wie Escherichia coli und Klebsiella pneumoniae vor. Hier sind die Trends der Resistenzen heterogen. Der Einsatz von Antibiotika führt zur Selektion von MRE, was gut dokumentiert ist. Erfolge bei der Minimierung des Antibiotikaeinsatzes konnten in zurückliegenden Jahren für einzelne Sektoren dargestellt und z. T. mit Erfolgen in der Eindämmung von AMR und MRE korreliert werden (Rückgang MRSA in der Humanmedizin). Auch sektorspezifische Maßnahmen zur Senkung der Last durch MRE und AMR sind notwendig, da Resistenzprobleme nicht generell eine Verknüpfung mit anderen Sektoren aufweisen. Carbapenemresistenzen sind vor allem bei pathogenen Erregern vom Menschen nachweisbar. Colistinresistenzen kommen in verschiedenen Sektoren vor, zeigen aber dort jeweils verschiedene Mechanismen. Resistenzen gegen Reservesubstanzen wie Linezolid sind in Deutschland selten, sie zeigen aber einen konkreten One-Health-Bezug. Bestrebungen zur Harmonisierung von Methoden, z. B. im Bereich der antimikrobiellen Empfindlichkeitstestung und genombasierten Erreger- und AMR-Surveillance, sind ein wichtiger erster Schritt zu einer Vergleichbarkeit der verschiedenen Datenerhebungen.One Health refers to a concept that links human, animal, and environmental health. In Germany, there is extensive data on antibiotic resistance (AMR) and multidrug-resistant (micro)organisms (MDRO) in human and veterinary medicine, as well as from studies in various environmental compartments (soil, water, wastewater). All these activities are conducted according to different specifications and standards, which makes it difficult to compare data. A focus on AMR and MDRO of human therapeutic importance is helpful to provide some guidance. Most data are available across sectors on methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Enterobacterales such as Escherichia coli and Klebsiella pneumoniae . Here, the trends of resistance are heterogeneous. Antibiotic use leads to MRE selection, which is well documented. Success in minimizing antibiotic use has also been demonstrated in recent years in several sectors and could be correlated with success in containing AMR and MDRO (e.g., decrease in MRSA in human medicine). Sector-specific measures to reduce the burden of MDRO and AMR are also necessary, as not all resistance problems are linked to other sectors. Carbapenem resistance is still rare, but most apparent in human pathogens. Colistin resistance occurs in different sectors but shows different mechanisms in each. Resistance to antibiotics of last resort such as linezolid is rare in Germany, but shows a specific One Health correlation. Efforts to harmonize methods, for example in the field of antimicrobial susceptibility testing and genome-based pathogen and AMR surveillance, are an important first step towards a better comparability of the different data collections