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Forschungsstelle
BLV
Projektnummer
1.15.08
Projekttitel
PRAHAD Prävalenz und optimierter Nachweis von Resistenz der für Tier- und Menschengesundheit lebenswichtigen Antibiotika (Uni Fribourg)
Projekttitel Englisch
Prevalence and optimised detection of resistance to antibiotics vital for animal and human health (Uni Fribourg)

Texte zu diesem Projekt
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Schlüsselwörter
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Kurzbeschreibung
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Erfasste Texte


KategorieText
Schlüsselwörter
(Deutsch)
Colistin, Aminoglycoside, Carbapenem, mobile Elemente, Diagnostik, Schwein, 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)

We have published a series of articles in relation with that project, in which the ANIWHA project has been acknowledged.

K. Zurfluh, R. Stephan, A. Widmer, L. Poirel, P. Nordmann, H.J. Nüesch, H. Hächler, M. Nüesch-Inderbinen. Screening for fecal carriage of MCR-producing Enterobacteriaceae in healthy humans and primary care patients. Antimicrobial Resistance and Infection Control 2017;6:28.

L. Poirel, N. Kieffer, P. Nordmann. In Vitro Study of ISApl1-Mediated Mobilization of the Colistin Resistance Gene mcr-1. Antimicrobial Agents and Chemotherapy 2017;61:e00127-17.

N. Kieffer, P. Nordmann, L. Poirel. Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants. Antimicrobial Agents and Chemotherapy 2017;61:e00129-17.

L. Poirel, N. Kieffer, J.F. Fernandez-Garayzabal, A.I. Vela, Y. Larpin, P. Nordmann MCR-2-mediated plasmid-borne polymyxin resistance most likely originates from Moraxella pluranimalium. Journal of Antimicrobial Chemotherapy 2017;72:2947-9.

L. Poirel, Y. Larpin, J. Dobias, R. Stephan, J.W. Decousser, J.Y. Madec, P. Nordmann. Rapid Polymyxin NP test for the detection of polymyxin resistance mediated by the mcr-1/mcr-2 genes. Diagnostic Microbiology and Infectious Diseases 2018;90:7-10.

N. Kieffer, M. Aires-de-Sousa, P. Nordmann, L. Poirel High Rate of MCR-1–Producing Escherichia coli and Klebsiella pneumoniae among Pigs, Portugal. Emerging Infectious Diseases 2017;23 :2023-2029.

Haenni M, Poirel L, Kieffer N, Châtre P, Saras E, Métayer V, Dumoulin R, Nordmann P, Madec JY. Co-occurrence of extended spectrum β lactamase and MCR-1 encoding genes on plasmids. Lancet Infect Dis. 2016;16:281-2.

Poirel L, Kieffer N, Brink A, Coetze J, Jayol A, Nordmann P. Genetic features of MCR-1-producing colistin-resistant Escherichia coli isolates, South Africa. Antimicrob Agents Chemother. 20;60:4394-4397.

Bontron S, Poirel L, Nordmann P. Real-time PCR for detection of plasmid-mediated polymyxin resistance (mcr-1) from cultured bacteria and stools. J Antimicrob Chemother. 2016;71:2318-2320.

Zurfuh K, Poirel L, Nordmann P, Nüesch-Inderbinen M, Hächler H, Stephan R. Occurrence of the plasmid-borne mcr-1 colistin resistance gene in ESBL-producing Enterobacteriaceae in river water and imported vegetable samples in Switzerland. Antimicrob Agents Chemother. 2016;60:2594-2595.

Gudeta DD, Bortolaia V, Jayol A, Poirel L, Nordmann P, Guardabassi L. Chromobacterium spp. harbour Ambler class A β-lactamases showing high identity with KPC. J Antimicrob Chemother. 2016;71:1493-1496.

Poirel L, Jayol A, Bontron S, Villegas MV, Ozdamar M, Türkoglu S, Nordmann P. (2015) The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae. J Antimicrob Chemother. 70:75-80.

Poirel L, Kieffer N, Liassine N, Thanh D, Nordmann P. Plasmid-mediated carbapenem and colistin resistance in a clinical isolate of Escherichia coli. Lancet Infect Dis. 2016;16:281. 

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