Macrolide resistance in Mannheimia haemolytica isolates associated with bovine respiratory disease from the German national resistance monitoring program GERM-Vet 2009 to 2020

Data collected from the German national resistance monitoring program GERM-Vet showed slowly increasing prevalence of macrolide resistance among bovine respiratory disease (BRD)-associated Pasteurellacae from cattle over the last decade. The focus of this study was to analyze the genetic basis of antimicrobial resistance (AMR) and the prevalence of multidrug-resistance (MDR)-mediating integrative and conjugative elements (ICEs) in 13 German BRD-associated Mannheimia haemolytica isolates collected between 2009 and 2020 via whole-genome sequencing. Antimicrobial susceptibility testing (AST) was performed via broth microdilution according to the recommendations of the Clinical and Laboratory Standards Institute for the macrolides erythromycin, tilmicosin, tulathromycin, gamithromycin, tildipirosin, and tylosin as well as 25 other antimicrobial agents. All isolates either had elevated MICs or were resistant to at least one of the macrolides tested. Analysis of whole-genome sequences obtained by hybrid assembly of Illumina MiSeq and Oxford Nanopore MinION reads revealed the presence of seven novel Tn7406-like ICEs, designated Tn7694, and Tn7724- Tn7729. These ICEs harbored the antimicrobial resistance genes erm(T), mef (C), mph(G), floR, catA3, aad(3“)(9), aph(3‘)-Ia, aac(3)-IIa, strA, strB, tet(Y), and sul2 in different combinations. In addition, mutational changes conferring resistance to macrolides, nalidixic acid or streptomycin, respectively, were detected among the M. haemolytica isolates. In addition, four isolates carried a 4,613-bp plasmid with the β-lactamase gene blaROB − 1. The detection of the macrolide resistance genes erm(T), mef (C), and mph(G) together with other resistance genes on MDR-mediating ICEs in bovine M. haemolytica may explain the occurrence of therapeutic failure when treating BRD with regularly used antimicrobial agents, such as phenicols, penicillins, tetracyclines, or macrolides. Finally, pathogen identification and subsequent AST is essential to ensure the efficacy of the antimicrobial agents applied to control BRD in cattle

Metabolic Characteristics of Porcine LA-MRSA CC398 and CC9 Isolates from Germany and China via Biolog Phenotype MicroArrayTM

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an important zoonotic pathogen, often multi-resistant to antimicrobial agents. Among swine, LA-MRSA of clonal complex (CC) 398 dominates in Europe, Australia and the Americas, while LA-MRSA-CC9 is the main epidemic lineage in Asia. Here, we comparatively investigated the metabolic properties of rare and widespread porcine LA-MRSA isolates from Germany and China using Biolog Phenotype MicroArray technology to evaluate if metabolic variations could have played a role in the development of two different epidemic LA-MRSA clones in swine. Overall, we were able to characterize the isolates’ metabolic profiles and show their tolerance to varying environmental conditions. Sparse partial least squares discriminant analysis (sPLS-DA) supported the detection of the most informative substrates and/or conditions that revealed metabolic differences between the LA-MRSA lineages. The Chinese LA-MRSA-CC9 isolates displayed unique characteristics, such as a consistently delayed onset of cellular respiration, and increased, reduced or absent usage of several nutrients. These possibly unfavorable metabolic properties might promote the ongoing gradual replacement of the current epidemic LA-MRSA-CC9 clone in China with the emerging LA-MRSA-CC398 lineage through livestock trade and occupational exposure. Due to the enhanced pathogenicity of the LA-MRSA-CC398 clone, the public health risk posed by LA-MRSA from swine might increase further

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

Vergleichende phänotypische und genotypische Untersuchungen von LA-MRSA CC398 und CC9 bei Schweinen aus Deutschland und China

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) are opportunistic zoonotic pathogens that have been globally recognized as a health threat in human and veterinary medicine. They are known for their common multiresistance to antimicrobial agents and may cause severe diseases although normally lacking major virulence factors. Colonized pigs and their related surroundings represent a considerable LA-MRSA reservoir. Due to their low host specificity, LA-MRSA isolates can easily cross species barriers. Therefore, persons with frequent (occupational) exposure to pigs have an increased risk of LA-MRSA colonization and/or infection and they may further transmit these isolates to contact persons and animals. The LA-MRSA prevalence differs geographically: Clonal Complex (CC) 398 dominates among pigs in Europe, Australia and the Americas, whereas CC9 is the most common lineage among pigs in Asia. This thesis revealed that differences in metabolic properties did most likely not play a key role in the development of the aforementioned two different epidemic porcine LA-MRSA clones in Germany and China, respectively. However, it was hypothesized that LA-MRSA CC398 might gradually replace the currently dominating CC9 lineage in China in the future because of many beneficial features that may enable preferential survival of the CC398 lineage under hostile environmental conditions or in the host. Possibly unfavorable metabolic variations and a lower growth rate of the Chinese LA-MRSA CC9 clone may be disadvantageous in niche adaptation and, thus, may support the replacement process. Consequently, the public health risk originating from porcine LA-MRSA might rise because of the increased pathogenicity of the CC398 lineage. Moreover, this thesis provided insight into population dynamics and molecular diversity of the epidemic porcine LA-MRSA CC398 lineage in Germany over 13 years in comparison with the porcine LA-MRSA CC9 lineage dominating in China. In general, both clones exhibited typical individual characteristics, but also some novel features. During comparison, similarities as well as distinct differences were recognized between the two lineages. The German CC398 isolates were widespread within Germany and largely reflected the pig density of the different regions. They displayed a wide molecular diversity and rather close phylogenetic relationships. An ongoing diversification was recognized over time. The CC398 and CC9 lineage both displayed a clear virulence potential, although genes coding for the major virulence factors Panton-Valentine leucocidin and toxic shock syndrome toxin-1 were not detected. Moreover, both lineages exhibited a great variety of AMR properties that mirrored the respective sales figures of veterinary antimicrobial agents in the two countries. The AMR profiles of the Chinese isolates were more extensive. In both lineages, AMR was largely associated with mobile genetic elements (MGEs), which can be transferred easily across strain, species or even genus boundaries via horizontal gene transfer (HGT). However, the German CC398 isolates displayed a greater variety of different MGEs, which points towards the easier integration of foreign genetic material. In addition, clonal and geographical correlations of molecular characteristics, virulence and resistance properties were more frequently observed among the LA-MRSA CC398 from Germany than temporal correlations. Furthermore, multiple novel MGEs were characterized in this thesis. A novel type V variant of the methicillin-resistance mediating SCCmec cassette was identified in a porcine LA-MRSA CC398 isolate from China. Homologies with other type V and XII elements indicate an ongoing evolution of SCCmec elements in LA-MRSA CC398 from pigs. Tn553 and Tn560 represent two new members of the Tn554 transposon family detected in Chinese LA-MRSA CC9 and CC398 isolates, respectively. Tn553 harbored a complete beta-lactam resistance mediating blaZ-blaR1-blaI beta-lactamase operon and preferred a different integration site than former Tn554-related transposons. Tn560 carried a multiresistance gene cluster comprising the spectinomycin resistance gene spcV, a novel spc variant that is most likely the product of a recombination between the related spc and spw genes, the pleuromutilin-lincosamide-streptogramin A resistance gene lsa(E) and the lincosamide resistance gene lnu(B). Plasmid pHKS3860 from a German porcine LA-MRSA CC398 isolate harbored the novel macrolide-lincosamide-streptogramin B resistance gene erm(54), cadmium, mercury and copper resistance genes, as well as an ica gene cluster for biofilm formation. As a consequence of such co-localizations on the same MGE, multiple resistance and/or virulence properties can be transferred in a single event. Even in the absence of a direct selection pressure, the risk for co-selection processes is increased. Finally, this thesis expanded the knowledge on the epidemic porcine LA-MRSA lineages in Germany and China. They represent a considerable AMR repository adding to the global health threat posed by AMR with HGT as major driver of rapid dissemination. Moreover, the understanding of genetic rearrangements in LA-MRSA and how these bacteria exchange genetic material has been improved. The diversity of LA-MRSA further increases and new emerging and possibly more virulent and/or resistant variants should be closely monitored. Due to the zoonotic potential and the risk of further spread among pig husbandries and into the human community, a full-scale LA-MRSA surveillance is vitally important.Nutztierassoziierte Methicillin-resistente Staphylococcus aureus (LA-MRSA) Isolate zählen zu den opportunistischen Zoonoseerregern, die weltweit in der Human- und Veterinärmedizin als Gesundheitsgefahr erkannt wurden. Diese Isolate sind für ihre häufige Multiresistenz gegenüber antimikrobiellen Wirkstoffen bekannt und können schwere Erkrankungen verursachen, obwohl ihnen normalerweise wesentliche Virulenzfaktoren fehlen. Kolonisierte Schweine und deren Umgebung stellen ein bedeutsames LA-MRSA-Reservoir dar. Aufgrund ihrer geringen Wirtsspezifität können LA-MRSA-Isolate leicht Speziesbarrieren überwinden. Daher haben Personen mit häufigem (beruflichen) Kontakt zu Schweinen ein erhöhtes Risiko für eine LA-MRSA-Besiedlung und/oder -Infektion und sie können diese Isolate weiter an Kontaktpersonen und -tiere übertragen. Die LA-MRSA-Prävalenz unterscheidet sich geografisch: Bei Schweinen in Europa, Australien und Nord- und Südamerika dominiert der klonale Komplex (CC) 398, während bei Schweinen in Asien CC9 die häufigste klonale Linie darstellt. In dieser These wurde gezeigt, dass unterschiedliche Stoffwechseleigenschaften höchstwahrscheinlich keine entscheidende Rolle bei der Entwicklung der beiden unterschiedlichen epidemischen LA-MRSA-Klone bei Schweinen in Deutschland beziehungsweise China spielten. Es wurde jedoch die Hypothese aufgestellt, dass LA-MRSA CC398 die derzeit in China dominierende CC9 Linie in Zukunft schrittweise ersetzen könnte, da viele vorteilhafte Eigenschaften der CC398 Linie ein bevorzugtes Überleben unter feindlichen Umweltbedingungen oder im Wirt ermöglichen könnten. Möglicherweise nachteilige Stoffwechselunterschiede und eine geringere Wachstumsrate des chinesischen LA-MRSA CC9 Klons könnten bei der Anpassung an ökologische Nischen von Nachteil sein und somit den Verdrängungsprozess unterstützen. Infolgedessen könnte das von porzinen LA-MRSA-Isolaten ausgehende Risiko für die öffentliche Gesundheit aufgrund der erhöhten Pathogenität der CC398 Linie ansteigen. Darüber hinaus lieferte diese These einen Einblick in die Populationsdynamik und die molekulare Diversität der epidemischen porzinen LA-MRSA CC398 Linie in Deutschland über einen Zeitraum von 13 Jahren im Vergleich zur porzinen LA-MRSA CC9 Linie, die in China dominiert. Im Allgemeinen wiesen beide Klone typische individuelle Merkmale, aber auch einige neuartige Eigenschaften auf. Beim Vergleich wurden sowohl Gemeinsamkeiten als auch deutliche Unterschiede zwischen den beiden Linien festgestellt. Die deutschen CC398 Isolate waren innerhalb Deutschlands weit verbreitet und spiegelten zu einem großen Teil die Schweinedichte der verschiedenen Regionen wider. Sie zeigten eine große molekulare Vielfalt und eher enge verwandtschaftliche Beziehungen. Über die Zeit wurde eine fortschreitende Diversifizierung festgestellt. Sowohl die CC398 als auch die CC9 Linie zeigten eindeutiges Virulenzpotenzial, obwohl Gene, die die wesentlichen Virulenzfaktoren Panton-Valentine-Leukozidin und Toxic-Shock-Syndrome-Toxin-1 kodieren, nicht nachgewiesen wurden. Außerdem besaßen beide Linien eine große Vielfalt an antimikrobiellenResistenzeigenschaften, die die jeweiligen Verkaufszahlen von tiermedizinisch genutzten antimikrobiellen Wirkstoffen in den beiden Ländern widerspiegelten. Die antimikrobiellen Resistenzprofile der chinesischen Isolate waren ausgeprägter. Bei beiden Linien war die antimikrobielle Resistenz größtenteils mit mobilen genetischen Elementen assoziiert, die durch horizontalen Gentransfer leicht über Stamm-, Spezies- oder sogar Gattungsgrenzen hinweg übertragen werden können. Allerdings wiesen die deutschen CC398 Isolate eine größere Vielfalt an unterschiedlichen mobilen genetischen Elementen auf, was auf eine erleichterte Aufnahme fremden genetischen Materials hindeutet. Weiterhin wurden klonale und geografische Korrelationen von molekularen Merkmalen, Virulenz- und Resistenzeigenschaften bei den LA-MRSA CC398 Isolaten aus Deutschland häufiger beobachtet als zeitliche Zusammenhänge. Außerdem wurden im Rahmen dieser These mehrere neue mobile genetische Elemente charakterisiert. Eine neue Typ-V-Variante der Methicillin-Resistenz vermittelnden SCCmec-Kassette wurde in einem porzinen LA-MRSA CC398 Isolat aus China identifiziert. Homologien mit anderen Typ-V- und -XII-Elementen deuten auf eine fortlaufende Evolution von SCCmec-Elementen in LA-MRSA CC398 Isolaten von Schweinen hin. Tn553 und Tn560 sind zwei neue Mitglieder der Tn554-Transposonfamilie, die in chinesischen LA-MRSA CC9 beziehungsweise CC398 Isolaten nachgewiesen wurden. Tn553 trug ein vollständiges Beta-Laktam-Resistenz vermittelndes blaZ-blaR1-blaI Beta-Laktamase-Operon und bevorzugte eine andere Integrationsstelle als vorherige Tn554-verwandte Transposons. Tn560 enthielt ein Multiresistenz-Gencluster bestehend aus dem Spectinomycin-Resistenzgen spcV, einer neuen spc-Variante, die wahrscheinlich das Produkt einer Rekombination zwischen den verwandten Genen spc und spw ist, dem Pleuromutilin-Lincosamid-Streptogramin-A-Resistenzgen lsa(E) und dem Lincosamid-Resistenzgen lnu(B). Das Plasmid pHKS3860 von einem deutschen porzinen LA-MRSA CC398 Isolat trug das neue Makrolid-Lincosamid-Streptogramin-B-Resistenzgen erm(54), Cadmium-, Quecksilber- und Kupferresistenzgene sowie ein ica-Gencluster für Biofilmbildung. Als Folge solcher Co-Lokalisationen auf demselben mobilen genetischen Element können mehrere Resistenz- und/oder Virulenzeigenschaften in einem einzigen Vorgang übertragen werden. Selbst wenn kein direkter Selektionsdruck besteht, ist das Risiko für Co-Selektionsprozesse erhöht. Abschließend hat diese These das Wissen über die epidemischen LA-MRSA-Linien bei Schweinen in Deutschland und China erweitert. Beide Linien stellen ein bedeutsames Repositorium antimikrobieller Resistenzgene dar, das zur globalen Gesundheitsbedrohung durch diese beiträgt, wobei der horizontale Gentransfer der wesentliche Faktor für eine schnelle Verbreitung ist. Darüber hinaus wurde das Verständnis der genetischen Umgestaltungen bei LA-MRSA-Isolaten und darüber wie diese Bakterien genetisches Material austauschen verbessert. Die Diversität von LA-MRSA-Isolaten nimmt weiter zu und neu auftretende, möglicherweise virulentere und/oder resistentere Varianten sollten genau beobachtet werden. Aufgrund des zoonotischen Potenzials und des Risikos einer weiteren Verbreitung innerhalb der Schweinehaltung und in die menschliche Gemeinschaft ist eine umfassende LA-MRSA-Überwachung von entscheidender Bedeutung

Table_1_Macrolide resistance in Mannheimia haemolytica isolates associated with bovine respiratory disease from the German national resistance monitoring program GERM-Vet 2009 to 2020.XLSX

Data collected from the German national resistance monitoring program GERM-Vet showed slowly increasing prevalence of macrolide resistance among bovine respiratory disease (BRD)-associated Pasteurellacae from cattle over the last decade. The focus of this study was to analyze the genetic basis of antimicrobial resistance (AMR) and the prevalence of multidrug-resistance (MDR)-mediating integrative and conjugative elements (ICEs) in 13 German BRD-associated Mannheimia haemolytica isolates collected between 2009 and 2020 via whole-genome sequencing. Antimicrobial susceptibility testing (AST) was performed via broth microdilution according to the recommendations of the Clinical and Laboratory Standards Institute for the macrolides erythromycin, tilmicosin, tulathromycin, gamithromycin, tildipirosin, and tylosin as well as 25 other antimicrobial agents. All isolates either had elevated MICs or were resistant to at least one of the macrolides tested. Analysis of whole-genome sequences obtained by hybrid assembly of Illumina MiSeq and Oxford Nanopore MinION reads revealed the presence of seven novel Tn7406-like ICEs, designated Tn7694, and Tn7724- Tn7729. These ICEs harbored the antimicrobial resistance genes erm(T), mef (C), mph(G), floR, catA3, aad(3“)(9), aph(3‘)-Ia, aac(3)-IIa, strA, strB, tet(Y), and sul2 in different combinations. In addition, mutational changes conferring resistance to macrolides, nalidixic acid or streptomycin, respectively, were detected among the M. haemolytica isolates. In addition, four isolates carried a 4,613-bp plasmid with the β-lactamase gene blaROB − 1. The detection of the macrolide resistance genes erm(T), mef (C), and mph(G) together with other resistance genes on MDR-mediating ICEs in bovine M. haemolytica may explain the occurrence of therapeutic failure when treating BRD with regularly used antimicrobial agents, such as phenicols, penicillins, tetracyclines, or macrolides. Finally, pathogen identification and subsequent AST is essential to ensure the efficacy of the antimicrobial agents applied to control BRD in cattle.</p

Table_2_Macrolide resistance in Mannheimia haemolytica isolates associated with bovine respiratory disease from the German national resistance monitoring program GERM-Vet 2009 to 2020.XLSX

Data collected from the German national resistance monitoring program GERM-Vet showed slowly increasing prevalence of macrolide resistance among bovine respiratory disease (BRD)-associated Pasteurellacae from cattle over the last decade. The focus of this study was to analyze the genetic basis of antimicrobial resistance (AMR) and the prevalence of multidrug-resistance (MDR)-mediating integrative and conjugative elements (ICEs) in 13 German BRD-associated Mannheimia haemolytica isolates collected between 2009 and 2020 via whole-genome sequencing. Antimicrobial susceptibility testing (AST) was performed via broth microdilution according to the recommendations of the Clinical and Laboratory Standards Institute for the macrolides erythromycin, tilmicosin, tulathromycin, gamithromycin, tildipirosin, and tylosin as well as 25 other antimicrobial agents. All isolates either had elevated MICs or were resistant to at least one of the macrolides tested. Analysis of whole-genome sequences obtained by hybrid assembly of Illumina MiSeq and Oxford Nanopore MinION reads revealed the presence of seven novel Tn7406-like ICEs, designated Tn7694, and Tn7724- Tn7729. These ICEs harbored the antimicrobial resistance genes erm(T), mef (C), mph(G), floR, catA3, aad(3“)(9), aph(3‘)-Ia, aac(3)-IIa, strA, strB, tet(Y), and sul2 in different combinations. In addition, mutational changes conferring resistance to macrolides, nalidixic acid or streptomycin, respectively, were detected among the M. haemolytica isolates. In addition, four isolates carried a 4,613-bp plasmid with the β-lactamase gene blaROB − 1. The detection of the macrolide resistance genes erm(T), mef (C), and mph(G) together with other resistance genes on MDR-mediating ICEs in bovine M. haemolytica may explain the occurrence of therapeutic failure when treating BRD with regularly used antimicrobial agents, such as phenicols, penicillins, tetracyclines, or macrolides. Finally, pathogen identification and subsequent AST is essential to ensure the efficacy of the antimicrobial agents applied to control BRD in cattle.</p

Metabolic Characteristics of Porcine LA-MRSA CC398 and CC9 Isolates from Germany and China via Biolog Phenotype MicroArrayTM

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an important zoonotic pathogen, often multi-resistant to antimicrobial agents. Among swine, LA-MRSA of clonal complex (CC) 398 dominates in Europe, Australia and the Americas, while LA-MRSA-CC9 is the main epidemic lineage in Asia. Here, we comparatively investigated the metabolic properties of rare and widespread porcine LA-MRSA isolates from Germany and China using Biolog Phenotype MicroArray technology to evaluate if metabolic variations could have played a role in the development of two different epidemic LA-MRSA clones in swine. Overall, we were able to characterize the isolates&rsquo; metabolic profiles and show their tolerance to varying environmental conditions. Sparse partial least squares discriminant analysis (sPLS-DA) supported the detection of the most informative substrates and/or conditions that revealed metabolic differences between the LA-MRSA lineages. The Chinese LA-MRSA-CC9 isolates displayed unique characteristics, such as a consistently delayed onset of cellular respiration, and increased, reduced or absent usage of several nutrients. These possibly unfavorable metabolic properties might promote the ongoing gradual replacement of the current epidemic LA-MRSA-CC9 clone in China with the emerging LA-MRSA-CC398 lineage through livestock trade and occupational exposure. Due to the enhanced pathogenicity of the LA-MRSA-CC398 clone, the public health risk posed by LA-MRSA from swine might increase further

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