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Prof. Dr. Guido Werner
Division of Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, National Reference Centre for Staphylococci and Enterococci, Wernigerode Branch, 38855 Wernigerode, Germany

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0 AMR
0 Genomics
0 Typing
0 Enterococci
0 Klebsiella

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Journal article
Published: 27 July 2021 in Antibiotics
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Dalbavancin is a lipoglycopeptide antibiotic that shows potent activity against Gram-positive bacteria. It circumvents vanB-type glycopeptide resistance mechanisms; however, data on the in vitro activity of dalbavancin for Enterococcus faecium (E. faecium) are scarce, and thus, no breakpoints are provided. In recent years, there has been a continuing shift from vanA-type to vanB-type vancomycin-resistance in enterococci in Central Europe. Therefore, we aimed to investigate the in vitro activity of dalbavancin against different van-genotypes, with particular focus on vanB-type E. faecium. Dalbavancin susceptibility was determined for 25 van-negative, 50 vanA-positive, and 101 vanB-positive clinical E. faecium isolates (typed by cgMLST). Epidemiological Cut-Off Values (ECOFFs) were determined using ECOFFinder. For vanB-type E. faecium isolates, dalbavancin MICs were similar to those of vancomycin-susceptible isolates reaching values no higher than 0.125 mg/L. ECOFFs for van-negative and vanB-positive isolates were 0.5 mg/l and 0.25 mg/L respectively. In contrast, E. faecium possessing vanA predominantly showed dalbavancin MICs >8 mg/L, therefore preventing the determination of an ECOFF. We demonstrated the potent in vitro activity of dalbavancin against vancomycin-susceptible and vanB-type E. faecium. On the basis of the observed wildtype distribution, a dalbavancin MIC of 0.25 mg/L can be suggested as a tentative ECOFF for E. faecium.

ACS Style

Robert Weber; Carola Fleige; Franziska Layer; Bernd Neumann; Michael Kresken; Guido Werner. Determination of a Tentative Epidemiological Cut-Off Value (ECOFF) for Dalbavancin and Enterococcus faecium. Antibiotics 2021, 10, 915 .

AMA Style

Robert Weber, Carola Fleige, Franziska Layer, Bernd Neumann, Michael Kresken, Guido Werner. Determination of a Tentative Epidemiological Cut-Off Value (ECOFF) for Dalbavancin and Enterococcus faecium. Antibiotics. 2021; 10 (8):915.

Chicago/Turabian Style

Robert Weber; Carola Fleige; Franziska Layer; Bernd Neumann; Michael Kresken; Guido Werner. 2021. "Determination of a Tentative Epidemiological Cut-Off Value (ECOFF) for Dalbavancin and Enterococcus faecium." Antibiotics 10, no. 8: 915.

Journal article
Published: 08 May 2021 in Pathogens
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The increase in infections with multidrug-resistant and virulent Klebsiella pneumoniae (K. pneumoniae) strains poses a serious threat to public health. However, environmental reservoirs and routes of transmission for Klebsiella spp. that cause infections in humans and in livestock animals are not well understood. In this study, we aimed to analyze the distribution of antibiotic resistance genes and important virulence determinants (ybt, clb, iro, iuc, rmpA/A2) among 94 Klebsiella spp. isolates from different animal and food sources isolated between 2013 and 2017 in Germany. Antibiotic susceptibility testing was performed, and the genomes were sequenced by Illumina and Nanopore technology. Genetic relationships were assessed by conducting core genome multilocus sequence typing (cgMLST). Kleborate was used to predict resistance and virulence genes; Kaptive was used to derive the capsule types. The results revealed that 72 isolates (76.6%) belonged to the K. pneumoniae sensu lato complex. Within this complex, 44 known sequence types (STs), 18 new STs, and 38 capsule types were identified. Extended-spectrum beta-lactamase (ESBL) genes were detected in 16 isolates (17.0%) and colistin resistance in one (1.1%) K. pneumoniae isolate. Virulence genes were found in 22 K. pneumoniae isolates. Overall, nine (9.6%) and 18 (19.1%) isolates possessed the genes ybt and iuc, respectively. Notably, aerobactin (iuc lineage 3) was only detected in K. pneumoniae isolates from domestic pigs and wild boars. This study provides a snapshot of the genetic diversity of Klebsiella spp. in animals and food products in Germany. The siderophore aerobactin was found to be more prevalent in K. pneumoniae strains isolated from pigs than other sources. Further investigations are needed to evaluate if pigs constitute a reservoir for iuc lineage 3.

ACS Style

Kathleen Klaper; Jens Hammerl; Jörg Rau; Yvonne Pfeifer; Guido Werner. Genome-Based Analysis of Klebsiella spp. Isolates from Animals and Food Products in Germany, 2013–2017. Pathogens 2021, 10, 573 .

AMA Style

Kathleen Klaper, Jens Hammerl, Jörg Rau, Yvonne Pfeifer, Guido Werner. Genome-Based Analysis of Klebsiella spp. Isolates from Animals and Food Products in Germany, 2013–2017. Pathogens. 2021; 10 (5):573.

Chicago/Turabian Style

Kathleen Klaper; Jens Hammerl; Jörg Rau; Yvonne Pfeifer; Guido Werner. 2021. "Genome-Based Analysis of Klebsiella spp. Isolates from Animals and Food Products in Germany, 2013–2017." Pathogens 10, no. 5: 573.

Journal article
Published: 30 March 2021 in Genome Medicine
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Background The hospital-adapted A1 group ofEnterococcus faeciumremains an organism of significant concern in the context of drug-resistant hospital-associated infections. How this pathogen evolves and disseminates remains poorly understood. Methods A large, globally representative collection of short-read genomic data from the hospital-associated A1 group ofEnterococcus faeciumwas assembled (n = 973). We analysed, using a novel analysis approach, global diversity in terms of both the dynamics of the accessory genome and homologous recombination among conserved genes. Results Two main modes of genomic evolution continue to shapeE. faecium: the acquisition and loss of genes, including antimicrobial resistance genes, through mobile genetic elements including plasmids, and homologous recombination of the core genome. These events lead to new clones emerging at the local level, followed by the erosion of signals of clonality through recombination, and in some identifiable cases producing new clonal clusters. These patterns lead to new, emerging lineages which are able to spread globally over relatively short timeframes. Conclusions The ability of A1E. faeciumto continually present new combinations of genes for potential selection suggests that controlling this pathogen will remain challenging but establishing a framework for understanding genomic evolution is likely to aid in tracking the threats posed by newly emerging lineages.

ACS Style

Sebastiaan J. van Hal; Enterococcal Group; Rob J. L. Willems; Theodore Gouliouris; Susan A. Ballard; Teresa M. Coque; Anette M. Hammerum; Kristin Hegstad; Hendrik T. Westh; Benjamin P. Howden; Surbhi Malhotra-Kumar; Guido Werner; Katsunori Yanagihara; Ashlee M. Earl; Katherine E. Raven; Jukka Corander; Rory Bowden. The global dissemination of hospital clones of Enterococcus faecium. Genome Medicine 2021, 13, 1 -12.

AMA Style

Sebastiaan J. van Hal, Enterococcal Group, Rob J. L. Willems, Theodore Gouliouris, Susan A. Ballard, Teresa M. Coque, Anette M. Hammerum, Kristin Hegstad, Hendrik T. Westh, Benjamin P. Howden, Surbhi Malhotra-Kumar, Guido Werner, Katsunori Yanagihara, Ashlee M. Earl, Katherine E. Raven, Jukka Corander, Rory Bowden. The global dissemination of hospital clones of Enterococcus faecium. Genome Medicine. 2021; 13 (1):1-12.

Chicago/Turabian Style

Sebastiaan J. van Hal; Enterococcal Group; Rob J. L. Willems; Theodore Gouliouris; Susan A. Ballard; Teresa M. Coque; Anette M. Hammerum; Kristin Hegstad; Hendrik T. Westh; Benjamin P. Howden; Surbhi Malhotra-Kumar; Guido Werner; Katsunori Yanagihara; Ashlee M. Earl; Katherine E. Raven; Jukka Corander; Rory Bowden. 2021. "The global dissemination of hospital clones of Enterococcus faecium." Genome Medicine 13, no. 1: 1-12.

Journal article
Published: 19 January 2021 in Antibiotics
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(1) Background: Resistance plasmids are under selective conditions beneficial for the bacterial host, but in the absence of selective pressure, this carriage may cause fitness costs. Compensation of this fitness burden is important to obtain competitive ability under antibiotic-free conditions. In this study, we investigated fitness effects after a conjugative transfer of plasmids containing various beta-lactamase genes transferred into Escherichia coli. (2) Methods: Fourteen beta-lactamase-encoding plasmids were transferred from clinical donor strains to E. coli J53. Growth rates were compared for all transconjugants and the recipient. Selected transconjugants were challenged in long-term growth experiments. Growth rates were assessed at different time points during growth for 500 generations. Whole-genome sequencing (WGS) of initial and evolved transconjugants was determined. Results: Most plasmid acquisitions resulted in growth differences, ranging from −4.5% to 7.2%. Transfer of a single blaCMY-16-carrying plasmid resulted in a growth burden and a growth benefit in independent mating. Long-term growth led to a compensation of fitness burdens and benefits. Analyzing WGS revealed genomic changes caused by Single Nucleotide Polymorphisms (SNPs) and insertion sequences over time. Conclusions: Fitness effects associated with plasmid acquisitions were variable. Potential compensatory mutations identified in transconjugants’ genomes after 500 generations give interesting insights into aspects of plasmid–host adaptations.

ACS Style

Michael Pietsch; Yvonne Pfeifer; Stephan Fuchs; Guido Werner. Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition of blaCMY-, blaCTX-M-, and blaOXA-48/VIM-1-Containing Plasmids in Escherichia coli. Antibiotics 2021, 10, 90 .

AMA Style

Michael Pietsch, Yvonne Pfeifer, Stephan Fuchs, Guido Werner. Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition of blaCMY-, blaCTX-M-, and blaOXA-48/VIM-1-Containing Plasmids in Escherichia coli. Antibiotics. 2021; 10 (1):90.

Chicago/Turabian Style

Michael Pietsch; Yvonne Pfeifer; Stephan Fuchs; Guido Werner. 2021. "Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition of blaCMY-, blaCTX-M-, and blaOXA-48/VIM-1-Containing Plasmids in Escherichia coli." Antibiotics 10, no. 1: 90.

Case report
Published: 08 January 2021 in Microorganisms
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Hypervirulent Klebsiella pneumoniae (hvKp) is a novel pathotype that has been rarely described in Europe. This study characterizes a hvKp isolate that caused a community-acquired infection. The hypermucoviscous Klebsiella pneumoniae (K. pneumoniae) strain 18-0005 was obtained from a German patient with tonsillopharyngitis in 2017. Antibiotic susceptibility testing was performed and the genome was sequenced by Illumina and Nanopore technology. Whole genome data were analyzed by conducting core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP) analysis. Virulence genes were predicted by applying Kleborate. Phenotypic and whole genome analyses revealed a high similarity of the study isolate 18-0005 to the recently reported antibiotic-susceptible hvKp isolate SB5881 from France and the “ancestral” strain Kp52.145; both were assigned to the ST66-K2 lineage. Comparative genomic analysis of the three plasmids showed that the 18-0005 plasmid II differs from SB5881 plasmid II by an additional 3 kb integrated fragment of plasmid I. Our findings demonstrate the genetic flexibility of hvKp and the occurrence of a strain of the clonal group CG66-K2 in Germany. Hence, it emphasizes the need to improve clinical awareness and infection monitoring of hvKp.

ACS Style

Kathleen Klaper; Sebastian Wendt; Christoph Lübbert; Norman Lippmann; Yvonne Pfeifer; Guido Werner. Hypervirulent Klebsiella pneumoniae of Lineage ST66-K2 Caused Tonsillopharyngitis in a German Patient. Microorganisms 2021, 9, 133 .

AMA Style

Kathleen Klaper, Sebastian Wendt, Christoph Lübbert, Norman Lippmann, Yvonne Pfeifer, Guido Werner. Hypervirulent Klebsiella pneumoniae of Lineage ST66-K2 Caused Tonsillopharyngitis in a German Patient. Microorganisms. 2021; 9 (1):133.

Chicago/Turabian Style

Kathleen Klaper; Sebastian Wendt; Christoph Lübbert; Norman Lippmann; Yvonne Pfeifer; Guido Werner. 2021. "Hypervirulent Klebsiella pneumoniae of Lineage ST66-K2 Caused Tonsillopharyngitis in a German Patient." Microorganisms 9, no. 1: 133.

Short communication
Published: 29 December 2020 in Diagnostic Microbiology and Infectious Disease
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The increasing number of nosocomial pathogens with resistances against last resort antibiotics like linezolid leads to a pressing need for the reliable detection of these drug-resistant bacteria. National guidelines on infection prevention, e.g., in Germany, have already recommend screening for linezolid-resistant bacteria, although a corresponding screening agar medium has not been provided. In this study we analyzed the performance and reliability of a commercial, chromogenic linezolid screening agar. The medium was capable to predict more than a hundred linezolid-resistant isolates of E. faecium, E. faecalis, S. aureus, S. epidermidis, and S. hominis with excellent sensitivity and specificity. All isolates were collected at the National Reference Centre between 2010 and 2020.

ACS Style

Franziska Layer; Robert E. Weber; Carola Fleige; Birgit Strommenger; Christiane Cuny; Guido Werner. Excellent performance of CHROMagarTM LIN-R to selectively screen for linezolid-resistant enterococci and staphylococci. Diagnostic Microbiology and Infectious Disease 2020, 99, 115301 .

AMA Style

Franziska Layer, Robert E. Weber, Carola Fleige, Birgit Strommenger, Christiane Cuny, Guido Werner. Excellent performance of CHROMagarTM LIN-R to selectively screen for linezolid-resistant enterococci and staphylococci. Diagnostic Microbiology and Infectious Disease. 2020; 99 (4):115301.

Chicago/Turabian Style

Franziska Layer; Robert E. Weber; Carola Fleige; Birgit Strommenger; Christiane Cuny; Guido Werner. 2020. "Excellent performance of CHROMagarTM LIN-R to selectively screen for linezolid-resistant enterococci and staphylococci." Diagnostic Microbiology and Infectious Disease 99, no. 4: 115301.

Preprint content
Published: 17 November 2020
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Antimicrobial resistance (AMR) poses an increasing challenge for therapy and clinical management of bacterial infections. Currently, antimicrobial resistance detection often relies on phenotypic assays, which are performed independently from species identification. Although genomics-based approaches are increasingly being proposed as possible alternatives for resistance detection, the analysis of proteins should be superior to gene or transcript sequencing when it comes to phenotype prediction from molecular data as the actual resistance against antibiotics is almost exclusively mediated by proteins. In this study, we present a unbiased proteomics workflow for detecting both, bacterial species and AMR related proteins in the absence of secondary antibiotic cultivation in less than 4 h from a primary culture. The method was validated using a sample cohort of 7 bacterial species and 11 AMR determinants represented by 13 protein isoforms which resulted in a sensitivity of 98 % (100 % with vancomycin inference) and a specificity of 100 % with respect to AMR determinants. This proof-of concept study suggests a high application potential of untargeted proteomics in clinical microbiology.

ACS Style

Christian Blumenscheit; Yvonne Pfeifer; Guido Werner; Charlyn John; Andy Schneider; Peter Lasch; Joerg Doellinger. Unbiased antimicrobial resistance detection from clinical bacterial isolates using proteomics. 2020, 1 .

AMA Style

Christian Blumenscheit, Yvonne Pfeifer, Guido Werner, Charlyn John, Andy Schneider, Peter Lasch, Joerg Doellinger. Unbiased antimicrobial resistance detection from clinical bacterial isolates using proteomics. . 2020; ():1.

Chicago/Turabian Style

Christian Blumenscheit; Yvonne Pfeifer; Guido Werner; Charlyn John; Andy Schneider; Peter Lasch; Joerg Doellinger. 2020. "Unbiased antimicrobial resistance detection from clinical bacterial isolates using proteomics." , no. : 1.

Review article
Published: 27 October 2020 in Drug Resistance Updates
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Enterococci are commensals of the intestinal tract of many animals and humans. Of the various known and still unnamed new enterococcal species, only isolates of Enterococcus faecium and Enterococcus faecalis have received increased medical and public health attention. According to textbook knowledge, the majority of infections are caused by E. faecalis. In recent decades, the number of enterococcal infections has increased, with the increase being exclusively associated with a rising number of nosocomial E. faecium infections. This increase has been accompanied by the dissemination of certain hospital-acquired strain variants and an alarming progress in the development of antibiotic resistance namely vancomycin resistance. With this review we focus on a description of the specific situation of vancomycin resistance among clinical E. faecium isolates in Germany over the past 30 years. The present review describes three VRE episodes in Germany, each of which is framed by the beginning and end of the respective decade. The first episode is specified by the first appearance of VRE in 1990 and a country-wide spread of specific vanA-type VRE strains (ST117/CT24) until the late 1990s. The second decade was initially marked by regional clusters and VRE outbreaks in hospitals in South-Western Germany in 2004 and 2005, mainly caused by vanA-type VRE of ST203. Against the background of a certain “basic level” of VRE prevalence throughout Germany, an early shift from the vanA genotype to the vanB genotype in clinical isolates already occurred at the end of the 2000s without much notice. With the beginning of the third decade in 2010, VRE rates in Germany have permanently increased, first in some federal states and soon after country-wide. Besides an increase in VRE prevalence, this decade was marked by a sharp increase in vanB-type resistance and a dominance of a few, novel strain variants like ST192 and later on ST117 (CT71, CT469) and ST80 (CT1065). The largest VRE outbreak, which involved about 2,900 patients and lasted over three years, was caused by a novel and until that time, unknown strain type of ST80/CT1013 (vanB). Across all periods, VRE outbreaks were mainly oligoclonal and strain types varied over space (hospital wards) and time. The spread of VRE strains obviously respects political borders; for instance, both vancomycin-variable enterococci which were highly prevalent in Denmark and ST796 VRE which successfully disseminated in Australia and Switzerland, were still completely absent among German hospital patients, until to date.

ACS Style

Guido Werner; Bernd Neumann; Robert E. Weber; Michael Kresken; Constanze Wendt; Jennifer K. Bender; Karsten Becker; Stefan Borgmann; Andreas Diefenbach; Axel Hamprecht; Michael Hogardt; Thomas Wichelhaus; Volkhard Kemp; Nils-Olaf Huebner; Achim Kaasch; Gernot Geginat; Wolfgang Kohnen; Alexander Menzer; T. Krause; Thomas Miethke; Felix Pranada; Florian Radojn; Steffen Tobisch; Verena Jansen; Thomas Regnath; Uwe Bührlen; Wulf Schneider-Brachert; Roman Schwarz; Michaela Luemen; Robert Skov; Alexander Thuermer; Heike von Baum; Michael Weig; Groß Uwe; Lutz Zabel; Hinrik von Wulffen; Stefanie Döring. Thirty years of VRE in Germany – “expect the unexpected”: The view from the National Reference Centre for Staphylococci and Enterococci. Drug Resistance Updates 2020, 53, 100732 .

AMA Style

Guido Werner, Bernd Neumann, Robert E. Weber, Michael Kresken, Constanze Wendt, Jennifer K. Bender, Karsten Becker, Stefan Borgmann, Andreas Diefenbach, Axel Hamprecht, Michael Hogardt, Thomas Wichelhaus, Volkhard Kemp, Nils-Olaf Huebner, Achim Kaasch, Gernot Geginat, Wolfgang Kohnen, Alexander Menzer, T. Krause, Thomas Miethke, Felix Pranada, Florian Radojn, Steffen Tobisch, Verena Jansen, Thomas Regnath, Uwe Bührlen, Wulf Schneider-Brachert, Roman Schwarz, Michaela Luemen, Robert Skov, Alexander Thuermer, Heike von Baum, Michael Weig, Groß Uwe, Lutz Zabel, Hinrik von Wulffen, Stefanie Döring. Thirty years of VRE in Germany – “expect the unexpected”: The view from the National Reference Centre for Staphylococci and Enterococci. Drug Resistance Updates. 2020; 53 ():100732.

Chicago/Turabian Style

Guido Werner; Bernd Neumann; Robert E. Weber; Michael Kresken; Constanze Wendt; Jennifer K. Bender; Karsten Becker; Stefan Borgmann; Andreas Diefenbach; Axel Hamprecht; Michael Hogardt; Thomas Wichelhaus; Volkhard Kemp; Nils-Olaf Huebner; Achim Kaasch; Gernot Geginat; Wolfgang Kohnen; Alexander Menzer; T. Krause; Thomas Miethke; Felix Pranada; Florian Radojn; Steffen Tobisch; Verena Jansen; Thomas Regnath; Uwe Bührlen; Wulf Schneider-Brachert; Roman Schwarz; Michaela Luemen; Robert Skov; Alexander Thuermer; Heike von Baum; Michael Weig; Groß Uwe; Lutz Zabel; Hinrik von Wulffen; Stefanie Döring. 2020. "Thirty years of VRE in Germany – “expect the unexpected”: The view from the National Reference Centre for Staphylococci and Enterococci." Drug Resistance Updates 53, no. : 100732.

Genome report
Published: 03 September 2020 in Gut Pathogens
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Colistin is still a widely used antibiotic in veterinary medicine although it is a last-line treatment option for hospitalized patients with infections caused by multidrug-resistant Gram-negative bacteria. Colistin resistance has gained additional importance since the recent emergence of mobile colistin resistance (mcr) genes. In the scope of a study on colistin resistance in clinical Escherichia coli isolates from human patients in Germany we characterized the mcr-1 gene variants. Our PCR-based screening for mcr-carrying E. coli from German patients revealed the presence of mcr-1-like genes in 60 isolates. Subsequent whole-genome sequence-based analyses detected one non-synonymous mutation in the mcr-1 gene for two isolates. The mutations were verified by Sanger sequencing and resulted in amino acid changes Met1Thr (isolate 803-18) and Tyr9Cys (isolate 844-18). Genotyping revealed no relationship between the isolates. The two clinical isolates were assigned to sequence types ST155 (isolate 803-18) and ST69 (isolate 844-18). Both mcr-1 variants were found to be located on IncX4 plasmids of 33 kb size; these plasmids were successfully conjugated into sodium azide resistant E. coli J53 Azir in a broth mating experiment. Here we present the draft sequences of E. coli isolate 803-18 carrying the novel variant mcr-1.26 and isolate 844-14 carrying the novel variant mcr-1.27. The results highlight the increasing issue of transferable colistin resistance.

ACS Style

Bernd Neumann; Wiebke Rackwitz; Klaus-Peter Hunfeld; Stephan Fuchs; Guido Werner; Yvonne Pfeifer. Genome sequences of two clinical Escherichia coli isolates harboring the novel colistin-resistance gene variants mcr-1.26 and mcr-1.27. Gut Pathogens 2020, 12, 1 -7.

AMA Style

Bernd Neumann, Wiebke Rackwitz, Klaus-Peter Hunfeld, Stephan Fuchs, Guido Werner, Yvonne Pfeifer. Genome sequences of two clinical Escherichia coli isolates harboring the novel colistin-resistance gene variants mcr-1.26 and mcr-1.27. Gut Pathogens. 2020; 12 (1):1-7.

Chicago/Turabian Style

Bernd Neumann; Wiebke Rackwitz; Klaus-Peter Hunfeld; Stephan Fuchs; Guido Werner; Yvonne Pfeifer. 2020. "Genome sequences of two clinical Escherichia coli isolates harboring the novel colistin-resistance gene variants mcr-1.26 and mcr-1.27." Gut Pathogens 12, no. 1: 1-7.

Journal article
Published: 21 August 2020 in International Journal of Environmental Research and Public Health
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Previously it was shown that application of probiotics stopped the acquisition of vancomycin-resistant Enterococcus faecium (VRE) by patients in an early rehabilitation ward. Once the application of probiotics ended, we examined whether acquisition of VRE reoccurred. Furthermore, we examined whether probiotics altered prevalence of vancomycin-susceptible E. faecium (VSE) and Gram-negative bacteria, which produce extended spectrum beta-lactamase (ESBL). Although probiotic application ceased in April 2018, VRE-colonized patients rarely presented on that ward until 2019. Probiotic treatment also resulted in a decreased number of patients with VSE and ESBL. While decreased incidence of VRE occurred immediately, decreased VSE and ESBL numbers occurred months later. A probiotic-mediated decrease of VSE and ESBL incidence cannot be explained when assuming bacterial transmission exclusively as a linear cause and effect event. The decrease is better understood by considering bacterial transmissions to be stochastic events, which depend on various driving forces similar to an electric current. We hypothesize that VRE, VSE and ESBL uptake by patients and by staff members mutually reinforced each other, leading staff members to form a bacterial reservoir, similar to a condenser that stores electrical energy. Probiotic treatment then inhibited regeneration of that store, resulting in a breakdown of the driving force.

ACS Style

Stefan Borgmann; Beate Rieß; David Meintrup; Ingo Klare; Guido Werner. Long-Lasting Decrease of the Acquisition of Enterococcus faecium and Gram-Negative Bacteria Producing Extended Spectrum Beta-Lactamase (ESBL) by Transient Application of Probiotics. International Journal of Environmental Research and Public Health 2020, 17, 6100 .

AMA Style

Stefan Borgmann, Beate Rieß, David Meintrup, Ingo Klare, Guido Werner. Long-Lasting Decrease of the Acquisition of Enterococcus faecium and Gram-Negative Bacteria Producing Extended Spectrum Beta-Lactamase (ESBL) by Transient Application of Probiotics. International Journal of Environmental Research and Public Health. 2020; 17 (17):6100.

Chicago/Turabian Style

Stefan Borgmann; Beate Rieß; David Meintrup; Ingo Klare; Guido Werner. 2020. "Long-Lasting Decrease of the Acquisition of Enterococcus faecium and Gram-Negative Bacteria Producing Extended Spectrum Beta-Lactamase (ESBL) by Transient Application of Probiotics." International Journal of Environmental Research and Public Health 17, no. 17: 6100.

Journal article
Published: 03 August 2020 in International Journal of Antimicrobial Agents
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Cefiderocol (CID, also known as S-649266), a novel siderophore cephalosporin, possesses potent activity against multidrug-resistant aerobic Gram-negative bacteria (GNB). The purpose of the present study was to determine the in vitro activity of CID against two different sets of GNB, i) a random sample of 213 clinical isolates, including 17 extended-spectrum beta-lactamase (ESBL) producers, obtained from intensive care unit (ICU) patients with nosocomial infections collected during a multicentre surveillance study (set I), and ii) a group of 59 challenge GNB producing various types of carbapenemases (CP; set II). Minimum inhibitory concentrations (MICs) were determined using the microdilution method according to the standard ISO 20776-1. Iron-depleted medium was used for testing CID. CID inhibited 97.2% of set I isolates at the EUCAST susceptibility breakpoint of ≤ 2 mg/l. The concentrations of CID inhibiting 50% and 90% (MIC50/90) of the Enterobacterales isolates (n=146) were 0.12/1 mg/l, with ESBL-positive isolates tending to exhibit higher MICs than ESBL-negative isolates to CID. MIC50/90 values of CID for isolates of the Acinetobacter baumannii group (n=13) and Pseudomonas aeruginosa (n=54) were 0.06/0.12 mg/l and 0.12/0.5 mg/l, respectively. Further, CID inhibited 88.1% of set II CP-producing isolates at ≤ 2 mg/l. All seven class D CP-producing A. baumannii were inhibited at ≤ 0.25 mg/l. MIC50/90 values for CP-producing Enterobacterales (n=30) and P. aeruginosa (n=22) were 1/4 mg/l and 0.5/2 mg/l, respectively. As a conclusion, CID showed potent activity against A. baumannii, Enterobacterales and P. aeruginosa, including CP-producing isolates. Overall, CID inhibited 259/272 (95.2%) GNB at ≤ 2 mg/l.

ACS Style

Michael Kresken; Miriam Korte-Berwanger; Sören G. Gatermann; Yvonne Pfeifer; Niels Pfennigwerth; Harald Seifert; Guido Werner. In vitro activity of cefiderocol against aerobic Gram-negative bacterial pathogens from Germany. International Journal of Antimicrobial Agents 2020, 56, 106128 .

AMA Style

Michael Kresken, Miriam Korte-Berwanger, Sören G. Gatermann, Yvonne Pfeifer, Niels Pfennigwerth, Harald Seifert, Guido Werner. In vitro activity of cefiderocol against aerobic Gram-negative bacterial pathogens from Germany. International Journal of Antimicrobial Agents. 2020; 56 (4):106128.

Chicago/Turabian Style

Michael Kresken; Miriam Korte-Berwanger; Sören G. Gatermann; Yvonne Pfeifer; Niels Pfennigwerth; Harald Seifert; Guido Werner. 2020. "In vitro activity of cefiderocol against aerobic Gram-negative bacterial pathogens from Germany." International Journal of Antimicrobial Agents 56, no. 4: 106128.

Technical advance
Published: 23 December 2019 in BMC Infectious Diseases
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Background Linezolid is an alternative treatment option for infections with multidrug-resistant Gram-positive bacteria including vancomycin-resistant enterococci. Some countries report an increasing number of isolates with resistance to linezolid. The recent publication of the Commission for Hospital Hygiene in Germany on enterococci/VRE recommends screening for linezolid-resistant enterococci (LRE). However, a suitable selective medium or a genetic test is not available. Our aim was to establish a selective screening agar for LRE detection and validate its application with a comprehensive collection of clinical LRE and linezolid-susceptible enterococci. Methods We decided to combine the selective power of an enterococcal screening agar with a supplementation of linezolid. Several rounds of analyses with reference, control and test strains and under varying linezolid concentrations of a wider and a smaller range were investigated and assessed. The collection of linezolid-resistant enterococcal control strains included isolates with different resistance mechanisms (23S rDNA mutations, cfr(B), optrA, poxtA). Finally, we validated our LRE screening agar with 400 samples sent to our National Reference Centre in 2019. Results Several rounds of pre-tests and confirmatory analyses favored Enterococcosel® Agar supplemented with a concentration of 2 mg/L linezolid. A 48 h incubation period was essential for accurate identification of LRE strains. Performance of the LRE screening agar revealed a sensitivity of 96.6% and a specificity of 94.4%. Conclusions Here we describe preparation of a suitable screening agar and a procedure to identify LRE isolates with high accuracy.

ACS Style

Guido Werner; Carola Fleige; Ingo Klare; Robert E. Weber; Jennifer K. Bender. Validating a screening agar for linezolid-resistant enterococci. BMC Infectious Diseases 2019, 19, 1 -5.

AMA Style

Guido Werner, Carola Fleige, Ingo Klare, Robert E. Weber, Jennifer K. Bender. Validating a screening agar for linezolid-resistant enterococci. BMC Infectious Diseases. 2019; 19 (1):1-5.

Chicago/Turabian Style

Guido Werner; Carola Fleige; Ingo Klare; Robert E. Weber; Jennifer K. Bender. 2019. "Validating a screening agar for linezolid-resistant enterococci." BMC Infectious Diseases 19, no. 1: 1-5.

Preprint content
Published: 09 October 2019
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Linezolid is an alternative treatment option for infections with multidrug-resistant Gram-positive bacteria including vancomycin-resistant enterococci (VRE). Some countries report an increasing number of isolates with resistance to linezolid. The recent publication of the Commission for Hospital Hygiene in Germany on enterococci/VRE recommends screening for linezolid-resistant enterococci (LRE). However, a suitable selective medium or a genetic test is not available. Our aim was to establish a selective screening agar for LRE detection and validate its application with a comprehensive collection of clinical LRE and linezolid-susceptible enterococci (LSE). We decided to combine the selective power of an enterococcal screening agar with a supplementation of linezolid. Several rounds of analyses with reference, control and test strains pointed towards Enterococcosel agar and a concentration of 2 mg/L linezolid. Finally, we validated our LRE agar with 400 samples sent to our National Reference Centre in 2019.

ACS Style

Guido Werner; Carola Fleige; Ingo Klare; Robert E. Weber; Jennifer K. Bender. Validating a screening agar for linezolid-resistant enterococci. 2019, 798983 .

AMA Style

Guido Werner, Carola Fleige, Ingo Klare, Robert E. Weber, Jennifer K. Bender. Validating a screening agar for linezolid-resistant enterococci. . 2019; ():798983.

Chicago/Turabian Style

Guido Werner; Carola Fleige; Ingo Klare; Robert E. Weber; Jennifer K. Bender. 2019. "Validating a screening agar for linezolid-resistant enterococci." , no. : 798983.

Journal article
Published: 28 August 2019 in Antimicrobial Resistance & Infection Control
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Due to limited therapeutic options, vancomycin-resistant Enterococcus faecium (VREF) is of great clinical significance. Recently, rising proportions of vancomycin resistance in enterococcal infections have been reported worldwide. This study aims to describe current epidemiological trends of VREF in German hospitals and to identify factors that are associated with an increased likelihood of vancomycin resistance in clinical E. faecium isolates. 2012 to 2017 data from routine vancomycin susceptibility testing of 35,906 clinical E. faecium isolates from 148 hospitals were analysed using data from the German Antimicrobial Resistance Surveillance System. Descriptive statistical analyses and uni- and multivariable regression analyses were performed to investigate the impact of variables, such as year of sampling, age and region, on vancomycin resistance in clinical E. faecium isolates. From 2014 onwards the proportions of clinical E. faecium isolates exhibiting resistance to vancomycin increased from 11.2% (95% confidence interval [CI] 9.4–13.3%) to 26.1% (95% CI 23.1–29.4%) in 2017. The rise of VREF proportions is primarily observed in the southern regions of Germany, whereas northern regions do not show a major increase. In the Southwest and Southeast, VREF proportions increased from 10.8% (95% CI 6.9–16.5%) and 3.8% (95% CI 3.0–11.5%) in 2014 to 36.7% (95% CI 32.9–40.8%) and 36.8% (95% CI 29.2–44.7%) in 2017, respectively. VREF proportions were considerably higher in isolates from patients aged 40–59 years compared to younger patients. Further regression analyses show that in relation to secondary care hospitals, E. faecium samples collected in specialist care hospitals and prevention and rehabilitation care centres are more likely to be vancomycin-resistant (odds ratios: 2.4 [95% CI 1.2–4.6] and 2.4 [95% CI 1.9–3.0], respectively). No differences in VREF proportions were found between female and male patients as well as between different clinical specimens. The proportion of VREF is increasing in German hospitals, particularly in southern regions in Germany. Increased efforts in infection control and antibiotic stewardship activities accounting for local resistance patterns are necessary to combat the spread of VREF in Germany.

ACS Style

Robby Markwart; Niklas Willrich; Sebastian Haller; Ines Noll; Uwe Koppe; Guido Werner; Tim Eckmanns; Annicka Reuss. The rise in vancomycin-resistant Enterococcus faecium in Germany: data from the German Antimicrobial Resistance Surveillance (ARS). Antimicrobial Resistance & Infection Control 2019, 8, 1 -11.

AMA Style

Robby Markwart, Niklas Willrich, Sebastian Haller, Ines Noll, Uwe Koppe, Guido Werner, Tim Eckmanns, Annicka Reuss. The rise in vancomycin-resistant Enterococcus faecium in Germany: data from the German Antimicrobial Resistance Surveillance (ARS). Antimicrobial Resistance & Infection Control. 2019; 8 (1):1-11.

Chicago/Turabian Style

Robby Markwart; Niklas Willrich; Sebastian Haller; Ines Noll; Uwe Koppe; Guido Werner; Tim Eckmanns; Annicka Reuss. 2019. "The rise in vancomycin-resistant Enterococcus faecium in Germany: data from the German Antimicrobial Resistance Surveillance (ARS)." Antimicrobial Resistance & Infection Control 8, no. 1: 1-11.

Journal article
Published: 23 July 2019 in Journal of Antimicrobial Chemotherapy
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Objectives In 2018, EUCAST issued a warning regarding unreliable results of gradient strip tests for confirming vancomycin resistance in enterococci. We compared the performance of various diagnostic standard and confirmatory tests to identify and determine vanB-type vancomycin resistance. Methods We analysed a collection of vanB-positive Enterococcus faecium isolates (n = 68) with low vancomycin MICs and compared the performance of VITEK® 2 (bioMérieux), broth microdilution and three gradient strip tests from different providers (Oxoid, Liofilchem and bioMérieux). For the latter we compared the standard procedure with a protocol with increased inoculum, a rich agar medium and a longer incubation time (‘macromethod’). Results The sensitivity of VITEK® 2 was 81% compared with 72% for broth microdilution and 61%–63% for the three gradient strip tests using standard conditions. The macromethod substantially improved the performance of all strip tests resulting in a sensitivity of 89%–96% after 48 h of incubation. Conclusions We recommend that EUCAST changes the present warning against the general use of MIC strips. When MIC strips are used to either exclude or confirm suspected vancomycin resistance in E. faecium, and a PCR is not available, the macromethod should be employed. For clinically relevant enterococci, where a rapid therapeutic decision is needed, a molecular test (e.g. PCR) should be favoured in order to save time and to further increase sensitivity.

ACS Style

Ingo Klare; Jennifer K Bender; Carola Fleige; Nancy Kriebel; Axel Hamprecht; Sören Gatermann; Guido Werner. Comparison of VITEK® 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs. Journal of Antimicrobial Chemotherapy 2019, 74, 2926 -2929.

AMA Style

Ingo Klare, Jennifer K Bender, Carola Fleige, Nancy Kriebel, Axel Hamprecht, Sören Gatermann, Guido Werner. Comparison of VITEK® 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs. Journal of Antimicrobial Chemotherapy. 2019; 74 (10):2926-2929.

Chicago/Turabian Style

Ingo Klare; Jennifer K Bender; Carola Fleige; Nancy Kriebel; Axel Hamprecht; Sören Gatermann; Guido Werner. 2019. "Comparison of VITEK® 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs." Journal of Antimicrobial Chemotherapy 74, no. 10: 2926-2929.

Preprint
Published: 10 May 2019
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ObjectivesIn 2018, EUCAST issued a warning regarding unreliable results of gradient strip tests for confirming vancomycin resistance in enterococci. We compared the performance of various diagnostic standard and confirmatory tests to identify and determine vanB-type vancomycin resistance.MethodsWe analysed a collection of vanB-positive E. faecium isolates (n = 68) with low level vancomycin minimal inhibitory concentrations (MICs) and compared the performance of Vitek® 2 (bioMérieux), of broth microdilution and of three different gradient strip test providers (Oxoid, Liofilchem, bioMérieux). For the latter we compared the standard procedure vs. a protocol with increased inoculum, a rich agar medium and a longer incubation time (“macromethod”).ResultsThe sensitivity of Vitek® 2 was 81% of vanB-isolates compared to 72% for broth microdilution and 61 – 63% for the three gradient strip tests using standard conditions. The “macromethod” substantially improved performance of all strip tests resulting in a sensitivity of 89 – 96% at 48h readout.ConclusionsThe “macromethod” provided the overall best performance for recognition of vanB E. faecium. We therefore propose to adapt the EUCAST warning and to recommend the “macromethod” with an additional 48h readout or a confirmation by a vanB-specific PCR from culture.

ACS Style

Ingo Klare; Jennifer K. Bender; Carola Fleige; Nancy Kriebel; Axel Hamprecht; Sören Gatermann; Guido Werner; Soeren Gatermann. Comparison of Vitek® 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs. 2019, 634535 .

AMA Style

Ingo Klare, Jennifer K. Bender, Carola Fleige, Nancy Kriebel, Axel Hamprecht, Sören Gatermann, Guido Werner, Soeren Gatermann. Comparison of Vitek® 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs. . 2019; ():634535.

Chicago/Turabian Style

Ingo Klare; Jennifer K. Bender; Carola Fleige; Nancy Kriebel; Axel Hamprecht; Sören Gatermann; Guido Werner; Soeren Gatermann. 2019. "Comparison of Vitek® 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs." , no. : 634535.

Journal article
Published: 30 March 2019 in Toxins
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Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widely disseminated as a nasal colonizer of conventionally raised livestock and of humans subjected to occupational exposure. Reports on contamination of raw meat raise the question as to whether occupationally exposed food handlers are at particular risk of nasal colonization by LA-MRSA. Here, we report the results from a cross-sectional study on nasal S. aureus/MRSA colonization of butchers, meat sellers, and cooks in Germany. We sampled 286 butchers and meat sellers in 26 butcheries and 319 cooks handling meat in 16 professional canteen kitchens. Swabs were processed on both blood agar plates and MRSA-selective plates. MRSA were confirmed by PCR for mec genes and by broth microdilution. All isolates were subjected to molecular typing. PCR for markers useful to differentiate human-adapted and animal-adapted subpopulations was performed due to the presence of clonal complexes known to occur in both livestock and humans (CC5, CC7, CC8, CC9, and CC398). Only two participants (0.33%) were colonized by MRSA (Hospital-associated MRSA ST22). Nasal colonization by methicillin-susceptible S. aureus (MSSA) was detected in 16.6% of cooks and in 26.2% of butchers and meat sellers. Among 16 of the isolates attributed to CC7, three were negative for the immune evasion gene cluster, suggesting an animal origin. Isolates attributed to CC5, CC8, and CC398 were negative for markers typical of animal-adapted subpopulations. The occupational handling of raw meat and raw meat products was not associated with nasal colonization by LA-MRSA.

ACS Style

Christiane Cuny; Franziska Layer; Sonja Hansen; Guido Werner; Wolfgang Witte. Nasal Colonization of Humans with Occupational Exposure to Raw Meat and to Raw Meat Products with Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus. Toxins 2019, 11, 190 .

AMA Style

Christiane Cuny, Franziska Layer, Sonja Hansen, Guido Werner, Wolfgang Witte. Nasal Colonization of Humans with Occupational Exposure to Raw Meat and to Raw Meat Products with Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus. Toxins. 2019; 11 (4):190.

Chicago/Turabian Style

Christiane Cuny; Franziska Layer; Sonja Hansen; Guido Werner; Wolfgang Witte. 2019. "Nasal Colonization of Humans with Occupational Exposure to Raw Meat and to Raw Meat Products with Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus." Toxins 11, no. 4: 190.

Journal article
Published: 14 November 2018 in Antimicrobial Resistance & Infection Control
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Infections caused by vancomycin-resistant enterococci (VRE) are on the rise worldwide. Few studies have tried to estimate the mortality burden as well as the financial burden of those infections and found that VRE are associated with increased mortality and higher hospital costs. However, it is unclear whether these worse outcomes are attributable to vancomycin resistance only or whether the enterococcal species (Enterococcus faecium or Enterococcus faecalis) play an important role. We therefore aimed to determine the burden of enterococci infections attributable to vancomycin resistance and pathogen species (E. faecium and E. faecalis) in cases of bloodstream infection (BSI). We conducted a retrospective cohort study on patients with BSI caused by Enterococcus faecium or Enterococcus faecalis between 2008 and 2015 in three tertiary care hospitals. Data was collected on true hospital costs (in €), length of stay (LOS), basic demographic parameters, and underlying diseases including the results of the Charlson comorbidity index (CCI). We used univariate and multivariable regression analyses to compare risk factors for in-hospital mortality and length of stay (i) between vancomycin-susceptible E. faecium- (VSEm) and vancomycin-susceptible E. faecalis- (VSEf) cases and (ii) between vancomycin-susceptible E. faecium- (VSEm) and vancomycin-resistant E. faecium-cases (VREm). We calculated total hospital costs for VSEm, VSEf and VREm. Overall, we identified 1160 consecutive cases of BSI caused by enterococci: 596 (51.4%) cases of E. faecium BSI and 564 (48.6%) cases of E. faecalis BSI. 103 cases of E. faecium BSI (17.3%) and 1 case of E. faecalis BSI (0.2%) were infected by vancomycin-resistant isolates. Multivariable analyses revealed (i) that in addition to different underlying diseases E. faecium was an independent risk factor for in-hospital mortality and prolonged hospital stay and (ii) that vancomycin-resistance did not further increase the risk for the described outcomes among E. faecium-isolates. However, the overall hospital costs were significantly higher in VREm-BSI cases as compared to VSEm- and VSEf-BSI cases (80,465€ vs. 51,365€ vs. 31,122€ p < 0.001). Our data indicates that in-hospital mortality and infection-attributed hospital stay in enterococci BSI might rather be influenced by Enterococcus species and underlying diseases than by vancomycin resistance. Therefore, future studies should consider adjusting for Enterococcus species in addition to vancomycin resistance in order to provide a conservative estimate for the burden of VRE infections.

ACS Style

Tobias Siegfried Kramer; Cornelius Remschmidt; Sven Werner; Michael Behnke; Frank Schwab; Guido Werner; Petra Gastmeier; Rasmus Leistner. The importance of adjusting for enterococcus species when assessing the burden of vancomycin resistance: a cohort study including over 1000 cases of enterococcal bloodstream infections. Antimicrobial Resistance & Infection Control 2018, 7, 1 -9.

AMA Style

Tobias Siegfried Kramer, Cornelius Remschmidt, Sven Werner, Michael Behnke, Frank Schwab, Guido Werner, Petra Gastmeier, Rasmus Leistner. The importance of adjusting for enterococcus species when assessing the burden of vancomycin resistance: a cohort study including over 1000 cases of enterococcal bloodstream infections. Antimicrobial Resistance & Infection Control. 2018; 7 (1):1-9.

Chicago/Turabian Style

Tobias Siegfried Kramer; Cornelius Remschmidt; Sven Werner; Michael Behnke; Frank Schwab; Guido Werner; Petra Gastmeier; Rasmus Leistner. 2018. "The importance of adjusting for enterococcus species when assessing the burden of vancomycin resistance: a cohort study including over 1000 cases of enterococcal bloodstream infections." Antimicrobial Resistance & Infection Control 7, no. 1: 1-9.

Journal article
Published: 17 September 2018 in International Journal of Antimicrobial Agents
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Ever since 2011, the National Reference Centre for Staphylococci and Enterococci in Germany receives an increasing number of linezolid-resistant Enterococcus (E.) spp. isolates. Although the majority belongs to the species E. faecium, clinical linezolid-resistant E. faecalis were isolated too. With respect to the newly discovered linezolid resistance protein OptrA, we herein conducted a retrospective PCR-screening of 698 linezolid-resistant Enterococcus clinical isolates. That yielded 43 optrA-positive strains of which a subset was analyzed by whole genome sequencing in order to infer linezolid resistance-associated mechanisms, phylogenetic relatedness and to disclose optrA genetic environments. Multiple optrA variants were detected. The originally described variant from China, optrAWT, was the only one shared between the two Enterococcus species; however, distinct optrAWT loci were detected for E. faecium and E. faecalis. Generally, optrA localized to a plethora of genetic backgrounds that differed even for identical optrA variants. This suggests transmission of a mobile genetic element harboring the resistance locus. Additionally, identical optrA variants detected on presumably identical plasmids, that were present in unrelated strains, indicates dissemination of the entire optrA-containing plasmid. In accordance, in vitro conjugation experiments verified transfer of optrA plasmids between enterococci of the same and of different species. In conclusion, multiple optrA variants located on distinct plasmids and mobile genetic elements with the potential of conjugative transfer are supposedly causative for the emergence of optrA-positive enterococci. Hence, rapid dissemination of the resistance determinant under selective pressure imposed by extensive use of last resort antibiotics in clinical settings could be expected.

ACS Style

Jennifer K. Bender; Carola Fleige; Dominik Lange; Ingo Klare; Guido Werner. Rapid emergence of highly variable and transferable oxazolidinone and phenicol resistance gene optrA in German Enterococcus spp. clinical isolates. International Journal of Antimicrobial Agents 2018, 52, 819 -827.

AMA Style

Jennifer K. Bender, Carola Fleige, Dominik Lange, Ingo Klare, Guido Werner. Rapid emergence of highly variable and transferable oxazolidinone and phenicol resistance gene optrA in German Enterococcus spp. clinical isolates. International Journal of Antimicrobial Agents. 2018; 52 (6):819-827.

Chicago/Turabian Style

Jennifer K. Bender; Carola Fleige; Dominik Lange; Ingo Klare; Guido Werner. 2018. "Rapid emergence of highly variable and transferable oxazolidinone and phenicol resistance gene optrA in German Enterococcus spp. clinical isolates." International Journal of Antimicrobial Agents 52, no. 6: 819-827.

Review
Published: 01 September 2018 in Drug Resistance Updates
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Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens. Invasive VRE infections are difficult to treat since common therapeutic options including ampicillin and glycopeptides often fail. In vitro, most VRE remain susceptible to last-resort antibiotics such as linezolid, tigecycline and daptomycin. However, neither tigecycline nor linezolid act in a bactericidal manner, and daptomycin has proven activity only at high dosages licensed for treating enterococcal endocarditis. Despite these pharmacological and therapeutic limitations, reports on resistance to these last-resort drugs in VRE, and enterococci in general, have increased in recent years. In this review, we briefly recapitulate the current knowledge on the mode of action as well as the known and novel mechanisms of resistance and describe surveillance data on resistance to linezolid, tigecycline and daptomycin in enterococci. In addition, we also suggest a common nomenclature for designating enterococci and VRE with resistances to these important last-resort antibiotics.

ACS Style

Jennifer K. Bender; Vincent Cattoir; Kristin Hegstad; Ewa Sadowy; Teresa M. Coque; Henrik Westh; Anette M. Hammerum; Kirsten Schaffer; Karen Burns; Stephen Murchan; Carla Novais; Ana Freitas; Luísa Peixe; Maria Del Grosso; Annalisa Pantosti; Guido Werner. Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: Towards a common nomenclature. Drug Resistance Updates 2018, 40, 25 -39.

AMA Style

Jennifer K. Bender, Vincent Cattoir, Kristin Hegstad, Ewa Sadowy, Teresa M. Coque, Henrik Westh, Anette M. Hammerum, Kirsten Schaffer, Karen Burns, Stephen Murchan, Carla Novais, Ana Freitas, Luísa Peixe, Maria Del Grosso, Annalisa Pantosti, Guido Werner. Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: Towards a common nomenclature. Drug Resistance Updates. 2018; 40 ():25-39.

Chicago/Turabian Style

Jennifer K. Bender; Vincent Cattoir; Kristin Hegstad; Ewa Sadowy; Teresa M. Coque; Henrik Westh; Anette M. Hammerum; Kirsten Schaffer; Karen Burns; Stephen Murchan; Carla Novais; Ana Freitas; Luísa Peixe; Maria Del Grosso; Annalisa Pantosti; Guido Werner. 2018. "Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: Towards a common nomenclature." Drug Resistance Updates 40, no. : 25-39.