PRAHAD Prävalenz und optimisierter Nachweis von Resistenz der für Tier- und Menschengesundheit lebenswichtigen Antibiotika (Uni Bern)

• Forschungsstelle: BLV
• Projektnummer: 1.15.07
• Projekttitel Englisch: Prevalence and optimised detection of resistance to antibiotics vital for animal and human health (Uni Bern)

Schlüsselwörter (Deutsch)

Colistin, Aminoglycoside, Carbapenem, mobile Elemente, Diagnostik, Schein, Rind, Resistenz, Prevalenz

Schlüsselwörter (Englisch)

Colistin, aminoglycosides, carbapenems, mobile elements, diagnostic tools, pig, cattle, resistance, prevalence

Kurzbeschreibung (Deutsch)

Die Auswahl an Antibiotika in der Medizin wird stetig kleiner, da immer mehr Bakterien gegen Antibiotika resistent sind. Es ist deshalb notwendig, alle möglichen Antibiotikaresistenzquellen zu identifizieren und unter Kontrolle zu bringen. Denn nur so können Übertragungen von Resistenzgenen zwischen Bakterien oder von resistenten Bakterien zwischen Tieren und/oder Menschen minimiert werden. Die Ziele des Anhiwa Projektes sind, die Resistenz gegen drei wichtige Klassen von Antibiotika in der Darmflora von Schweinen und Rindern zu untersuchen; Polymyxin (Colistin), Aminoglykoside und Carbapeneme.

Dieses Projekt wird die Resistenzraten (oder reduzierte Empfindlichkeit) von Colistin, Aminoglykoside und Carbapeneme bei Gram-negativen Enterobakterien von Schweinen und Rindern auswerten. Zudem werden die Resistenzmechanismen und ihre genetische Umgebung identifiziert. Falls kein bekannter Resistenzmechanismus identifiziert werden kann, werden die Stämme mittels Sequenzierung und Metagenomik untersucht um den neuen Resistenzmechanismus zu identifizieren. Resulate aus den verschiedenen Ländern werden untereinander verglichen.

Die Identifizierung von Carbapenemase-produzierenden Isolaten wird in einem ersten Schritt mittels einer Schnelldiagnosemethode durchgeführt. Weitere diagnostische Methoden werden entwickelt, um auch die Colistin- und Aminoglykosidresitenzen schnell identifizieren zu können. Der Einsatz von Antibiotika in der Tiermedizin, die Antibiotikaresistenz und die mögliche Übertragung von resistenten Bakterien auf den Menschen durch die Nahrungskette sind Themen mit hoher Priorität auf nationaler und internationaler Ebene. Umfassende EU-weite wissenschaftlichen Daten sind notwendig um politische Entscheidung zu Unterstützen, sodass die Tier- und Menschengesundheit sowie deren Wohlbefinden gewährleistet bleibt. Rückverfolgbarkeit und Transparenz in der Tier- und Lebensmittelproduktion sind von entscheidender Bedeutung um sichere und hohe Standards in der Tiergesundheit und im Tierschutz zu gewährleisten.

Kurzbeschreibung (Englisch)

The arsenal of antibiotics for use in medicine is ever decreasing, while the rates of resistance are ever increasing. There is a great need to identify and control all sources of antibiotic resistance, and minimize the transfer of resistance genes and/or bacteria within animals and between animals and humans. The aims of this collaborative project are to address resistance to three critically important classes of antibiotic classes; polymyxins (colistin), aminoglycosides and carbapenems among gut microflora from pigs and cattle. Colistin is an important antibiotic in the treatment of animals with intestinal infections i.e. Escherichia coli and Salmonella species. Carbapenemases were thought to be restricted to human pathogens, since carbapenems are not used in veterinary medicine. However, they have recently been identified in food animals.

This project will evaluate the rates of resistance (or reduced susceptibility) to colistin, aminoglycosides and carbapenems and among Gram negative enteric bacteria from pigs and cattle, and compare these with the levels of prescribing in the different countries. We will identify the mechanisms leading to the resistance or reduced susceptibility to those antibiotics, and decipher their genetic environment. In cases where no known resistance mechanism can be identified we will utilise whole genome sequencing and functional metagenomics to decipher the novel resistance mechanism. Using this data we can then evaluate the relationship between mobile resistance elements within and between countries.

Recently-developed rapid diagnostic techniques for cheap identification of carbapenemase-producing isolates will be applied to investigate carbapenem resistance. We will also develop further diagnostic tools for the identification of colistin and aminoglycoside resistances. The use of antibiotics in veterinary medicine, the emergence of antibiotic resistance and the potential transfer of resistance through the food chain to humans are topics of high priority at both the national and EU policy levels. Comprehensive EU-wide scientific data is required to guide future policy in this area and to ensure the maintenance of both animal and human health and welfare. Traceability and transparency within the food industry are vital to build on the reputation that Europe has built up over many years as an area of safe food production, with high standards in animal health and welfare.

Projektziele (Englisch)

The aims of this collaborative project are to address resistance to three critically important classes of antibiotic classes, namely polymyxins (colistin), broad-spectrum aminoglycosides and carbapenems among bacterial isolates from pigs and cattle. Colistin is internationally authorized for use in veterinary medicine, and is used at varying levels within Europe e.g., 64.96 t in France, 1.68 t in Switzerland, and 0.7 t in Ireland. Recently, plasmid-mediated 16S rRNA methylases conferring resistance to all aminoglycosides (except streptomycin) including the clinically-important amikacin have emerged in human isolates, and have also been recently reported in animals. Acquired carbapenem resistance through the production of carbapenemases has been recently reported in both pig and cattle gut microbiota, despite the fact that they are not used in food-producing animals. Surveillance programs of antibiotic resistance in food-producing animals do not monitor resistance to colistin, aminoglycosides or carbapenems using specifically adequate tools and therefore their prevalence remains unknown.

Specific aims

1. To evaluate the rates of resistance (or reduced susceptibility) to colistin, aminoglycosides and carbapenems among Gram negative bacteria from the gut microflora of pigs and cattle, and compare these data with the levels of prescribing in the different countries.

2. To develop rapid diagnostic tests for the identification of colistin and aminoglycoside resistant isolates and apply recently-developed diagnostic techniques for the rapid and cheap identification of carbapenemase-producing isolates.

3. To identify the mechanisms (known and novel) leading to the resistance or reduced susceptibility to colistin, aminoglycoside and carbapenem antibiotics.

4. To elucidate the genetic environments of the mobile resistance mechanisms.

Publikationen / Ergebnisse (Englisch)

Perreten, V.; Strauss, C.; Collaud, A.; Gerber, D. (2016) Colistin resistance gene mcr-1 in avian-pathogenic Escherichia coli in South Africa. Antimicrob Agents Chemother. 2016 Jun 20;60(7):4414-5.

Donà, V.; Bernasconi, O.J.; Pires, J.; Collaud, A.; Overesch, G.; Ramette, A.; Perreten, V.; Endimiani, A. (2017) Heterogeneous genetic location of mcr-1 in colistin-resistant Escherichia coli isolates from humans and retail chicken meat in Switzerland: Emergence of mcr-1-carrying IncK2 plasmids. Antimicrob  Agents Chemother. 2017 Oct 24;61(11). pii: e01245-17.

Brilhante, M.; Perreten, V.; Donà, V. (2018) Multidrug resistance and multivirulence plasmids in enterotoxigenic and hybrid Shiga toxin-producing/enterotoxigenic Escherichia coli isolated from diarrheic pigs in Switzerland. Vet. J. 2018, under revision

Perreten, V.; Overesch, G. (2016) Acquired colistin resistance gene mcr-1 in imported chicken meat. Text box in ARCH-Vet - anresis joint report 2016.

Perreten, V.; Overesch, G. (2016) Colistin resistance in pigs and calves, Switzerland 2015. Text box in ARCHVet - anresis joint report 2016.

Donà, V.; Brand, P.A.; Gobeli, S.; Endimiani, A.; Perreten, V. (2017) Complete nucleotide sequence of a multidrug- resistance plasmid from an enterotoxigenic Escherichia coli K88 from pig. Joint Annual Meeting 2017 of the Swiss Societies for Microbiology (SSM), for Infectious Diseases (SSI), Hospital Hygiene (SSHH), Tropical Medicine and Parasitology (SSTMP) and the Swiss Society of Tropical and Travel Medicine (SSTTM), Basel, Switzerland, 30 August – 1 September 2017. Poster presentation

Donà, V.; Bernasconi, O.J.; Perreten, V.; Endimiani, A. (2017) Heterogeneous location of the mcr-1 gene in colistin-resistant Escherichia coli strains from humans and chicken meat. 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna, Austria, 22 – 25 April 2017. Poster presentation

Perreten V. (2017) Antibiotika-Resistenz: Entwicklung und Verbreitung. Informationsnachmittag für Fleischproduzenten und Tierärtze, Suisseporcs Höck, Hildisrieden, 3. April 2017.

Perreten V. (2016) Antibiotika-Resistenz: Entwicklung und Verbreitung. Informationsnachmittag für Fleischproduzenten und Tierärtze, ASF Sursee, 22. November 2016.

Brilhante, M.; Perreten, V.; Donà, V. (2018) Characterization of multidrug resistance plasmids harbored in enterovirulent Escherichia coli isolated from diarrheic pigs in Switzerland. Annual Swiss Society for Microbiology Meeting 2018. Lausanne, Switzerland. 28 – 30 August 2018. Oral presentation.

Donà, V.; Bernasconi, O.J.; Perreten, V.; Endimiani, A. (2017) Genetic environment of the mcr-1 gene in colistin- resistant E. coli strains of human and chicken meat origin. Joint meeting of the "Club de Pathologie Infectieuse" and the “Réunion Informelle“ of the Swiss Society for Microbiology, Inselspital, Bern, Switzerland, 9 February 2017. Oral presentation

Brilhante, M. (2018) Multidrug resistance plasmids in enterotoxigenic and Shiga toxin-producing Escherichia coli isolated from diarrheic pigs in Switzerland. Host-Pathogen Interactions and Drug Resistance Symposium, Bern, Switzerland, 4th May 2018. Oral presentation

1] Poirel L, Jayol A, Nordmann P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin Microbiol Rev 2017;30:557–96.
[2] Donà V, Bernasconi OJ, Pires J, Collaud A, Overesch G, Ramette A, et al. Heterogeneous genetic location of mcr-1 in colistin-resistant Escherichia coli isolates from humans and retail chicken meat in Switzerland: emergence of mcr-1-carrying IncK2 plasmids. Antimicrob Agents Chemother 2017;61: e01245-17.

Zugehörige Dokumente

• 1.15.07 DB/SB [PDF] 133 kB
• Donà et al. Emergence of mcr-1 [PDF] 918 kB
• Perreten et al. Escherichia coli [PDF] 451 kB

URL-Adressen (Deutsch)

1.15.07 Perreten PRAHAD Prävalenz und optimisierter Nachweis von Resistenz der für Tier- und Mensch…