G Werner

Publications of G Werner

• Emergence and spread of vancomycin resistance among enterococci in Europe.

  Authors: G Werner, Tm Coque, Am Hammerum, R Hope, W Hryniewicz, A Johnson, I Klare, Kg Kristinsson, R Leclercq, Ch Lester [......] C Novais, B. Olsson-Liljequist, Lv Peixe, E Sadowy, Gs Simonsen, J. Top, J Vuopio-Varkila, Rj Willems, W Witte, N Woodford

  Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin. 12/2008; 13(47).

  Nowadays, six types of acquired vancomycin resistance in enterococci are known; however, only VanA and to a lesser extent VanB are widely prevalent. Various genes encode acquired vancomycinNowadays, six types of acquired vancomycin resistance in enterococci are known; however, only VanA and to a lesser extent VanB are widely prevalent. Various genes encode acquired vancomycin resistance and these are typically associated with mobile genetic elements which allow resistance to spread clonally and laterally.

• Discrimination between epidemic and non-epidemic glycopeptide-resistant E. faecium in a post-outbreak situation.

  Authors: S Borgmann, B Schulte, C Wolz, H Gruber, G Werner, C Goerke, I Klare, K Beyser, P Heeg, I B Autenrieth

  The Journal of hospital infection. 10/2007; 67(1):49-55.

  Vancomycin-resistant enterococci (VRE) have been isolated in increasing numbers. Hospital-adapted VRE exhibit relatively high pathogenicity by expressing factors like enterococcal surface proteinVancomycin-resistant enterococci (VRE) have been isolated in increasing numbers. Hospital-adapted VRE exhibit relatively high pathogenicity by expressing factors like enterococcal surface protein (Esp), which facilitates epidemic spread. By contrast, 'community-acquired' VRE show low pathogenicity and non-epidemic features. In 2004 and 2005 an extended outbreak of VRE occurred at a university hospital in Southwestern Germany and an infection control programme was implemented to confine the outbreak. Pulsed-field gel electrophoresis (PFGE), esp PCR, multiple-locus variable number of tandem repeat analysis (MLVA), purK1 typing and multiple-locus sequence typing (MLST) were performed on representative VRE isolates. Twenty-six non-epidemic and two epidemic VRE types (MLST203, MLST280) were identified by PFGE. Seven of the non-outbreak VRE types were esp gene negative, whereas 19 non-outbreak and both epidemic VRE types were esp positive. Eight MLVA types were identified. MLVA type 1 included five PFGE types and MLVA type 159 included 16 PFGE types. Currently there is no efficient method available to identify non-epidemic VRE and avoid unnecessary isolation of patients. More than 50% non-epidemic clones were esp positive; nevertheless, esp PCR appears to be the most promising approach to identify non-epidemic VRE.

• [Prevention and control of the spread of vancomycin-resistant enterococci: results of a workshop held by the German Society for Hygiene and Microbiology]

  Authors: R-P Vonberg, I F Chaberny, A Kola, F Mattner, S Borgmann, M Dettenkofer, D Jonas, A M Fahr, I Klare, G Werner, K Weist, C Wendt, P Gastmeier

  Der Anaesthesist. 03/2007; 56(2):151-7.

  The incidence of vancomycin-resistant enterococci (VRE), especially E. faecium, is increasing in several German hospitals and some facilities have experienced VRE outbreaks. The German NationalThe incidence of vancomycin-resistant enterococci (VRE), especially E. faecium, is increasing in several German hospitals and some facilities have experienced VRE outbreaks. The German National Nosocomial Infection Surveillance System has also noticed a sharp increase in the incidence of nosocomial VRE infections per 10,000 patients from 0.5 in 2003 to 11.0 in 2005 accompanied by a rise in VRE-associated mortality. However, the reasons of this increase remain unknown. As VRE may cause severe nosocomial infections, transmission must be restricted. This article provides the guidelines as defined by the workshop of the German Society for Hygiene and Microbiology for the prevention of VRE transmission in both, endemic and epidemic, settings. The following topics are discussed: indication for VRE screening, microbiological diagnostics, general infection control measures (isolation precautions and use of protective clothing) and additional hygiene measures in the nosocomial VRE outbreak setting.

• Spread of ampicillin/vancomycin-resistant Enterococcus faecium of the epidemic-virulent clonal complex-17 carrying the genes esp and hyl in German hospitals.

  Authors: I Klare, C Konstabel, S Mueller-Bertling, G Werner, B Strommenger, C Kettlitz, S Borgmann, B Schulte, D Jonas, A Serr, A M Fahr, U Eigner, W Witte

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 01/2006; 24(12):815-25.

  The incidence of vancomycin-resistant Enterococcus faecium isolation was low (<or=5%) in German hospitals before 2003. Within the second half of 2003 and the first half of 2004, however, increasingThe incidence of vancomycin-resistant Enterococcus faecium isolation was low (<or=5%) in German hospitals before 2003. Within the second half of 2003 and the first half of 2004, however, increasing frequencies of up to 14% were noticed in several hospitals in southwestern Germany. This increase was attributed mainly to the occurrence and spread of epidemic-virulent ampicillin/vancomycin-resistant, vanA- and vanB-positive E. faecium clones, most of which exhibited the virulence factors enterococcal surface protein (esp) and bacteriocin activity and some which exhibited hyaluronidase (hyl). E. faecium possessing hyaluronidase was initially found in U.S. hospitals and recently detected in several European hospitals and, subsequently, in German hospitals as well. Ampicillin/vancomycin-resistant E. faecium clones originating mainly from southwestern German hospitals were characterized by multilocus sequence typing since different sequence types (STs) belonging to the clonal complex-17 are currently disseminated worldwide. Multilocus sequence typing revealed that, in 1998 and 1999, ampicillin/vancomycin-resistant E. faecium clone ST-117 was prevalent in various German hospitals, while in 2003 and 2004, clone ST-203 dominated in several hospitals located in southwestern Germany. Both sequence types display single-locus variants of ST-78, which was frequently recorded in various Italian hospitals between 2000 and 2003, and all of these STs belong to the clonal complex-17. Expression of linezolid resistance was observed in ampicillin/glycopeptide-resistant E. faecium strains (VanA type) from two tertiary hospitals in southwestern Germany due to mutations in domain V of the 23S rDNA (G2576T). While in one hospital the resistance emerged during linezolid therapy, in the other hospital resistance was caused by transfer of an identical linezolid/ampicillin/glycopeptide-resistant E. faecium strain. In conclusion, it is very important to monitor the occurrence of epidemic-virulent clonal complex-17 strains of E. faecium to prevent their spread in hospitals, especially if they are resistant to glycopeptides and linezolid.

• Emergence of methicillin-resistant Staphylococcus aureus with Panton-Valentine leukocidin genes in central Europe.

  Authors: W Witte, C Braulke, C Cuny, B Strommenger, G Werner, D Heuck, U Jappe, C Wendt, H J Linde, D Harmsen

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 02/2005; 24(1):1-5.

  The aim of the present study was to investigate strains of methicillin-resistant Staphylococcus aureus (MRSA) for the presence of the lukS-lukF determinant of Panton-Valentine leukocidin and toThe aim of the present study was to investigate strains of methicillin-resistant Staphylococcus aureus (MRSA) for the presence of the lukS-lukF determinant of Panton-Valentine leukocidin and to further characterize strains found to contain the genes. During the past 2 years, MRSA containing the lukS-lukF genes for Panton-Valentine leukocidin, particularly those emerging outside of hospitals, have become of interest. MRSA strains sent to the national reference center in Germany were investigated for lukS-lukF by polymerase chain reaction (PCR). If the presence of lukS-lukF was demonstrated, strains were further characterized by molecular typing (determination of SmaI pattern, spa sequence, and multilocus sequence type), PCR demonstration of resistance genes, and characterization of the SCCmec element. Since the end of 2002, MRSA containing Panton-Valentine leukocidin genes have been demonstrated as the causative agent of 28 cases of infection (9 community-acquired cases, 19 sporadic nosocomial cases) in different areas of Germany. Twenty-seven of these 28 isolates exhibited a unique pattern of genomic typing: all exhibited multilocus sequence type 80, spa sequence type 44, and a SmaI macrorestriction pattern that corresponds to a community-acquired strain of MRSA from France and Switzerland. In addition to resistance to oxacillin, the strains exhibited resistance to ciprofloxacin, tetracycline (tetM), and fusidic acid, the last of which is encoded by the far-1 gene. The far-1 gene was shown to be located on the plasmid. One isolate corresponded to community MRSA (cMRSA) of multilocus sequence type 1 from the USA.

• Linezolid-resistant Enterococcus faecium and Enterococcus faecalis isolated from a septic patient: report of first isolates in Germany.

  Authors: E Halle, J Padberg, S Rosseau, I Klare, G Werner, W Witte

  Infection. 07/2004; 32(3):182-3.

  Here we report the first German case of necrotizing pancreatitis, peritonitis, and septic shock caused by linezolid-resistant Enterococcus faecium and Enterococcus faecalis.

• [Antibiotic-resistant nosocomial pathogens. Part I: diagnostic and typing methods]

  Authors: W Witte, B Strommenger, I Klare, G Werner

  Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz. 05/2004; 47(4):352-62.

  For use in human chemotherapy, there are several different substances for nearly each substance group available which cannot all be checked in routine susceptibility testing. If the bacterialFor use in human chemotherapy, there are several different substances for nearly each substance group available which cannot all be checked in routine susceptibility testing. If the bacterial resistance mechanisms and cross-resistance conferred by them are known, particular test substances can be selected and the results are interpreted on the basis of cross-resistance. Test substances correspond to those mentioned in guidelines for section sign 23 IfSG (German law on protection against infection). Due to suboptimal in vitro expression of different resistance mechanisms, it is necessary to perform additional tests besides routine agar-diffusion or microbroth MIC assays. These are preferentially tests for molecular demonstration of resistance genes. Emergence and spread of antibiotic-resistant nosocomial pathogens can be traced by typing. When selecting a typing method, it is important to assess work load, discriminatory power, and reproducibility. In future the availability of microarray technology will enable routine laboratories to demonstrate particular virulence-associated traits.

• Obvious lack of association between dynamics of epidemic methicillin-resistant Staphylococcus aureus in central Europe and agr specificity groups.

  Authors: B Strommenger, C Cuny, G Werner, W Witte

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 02/2004; 23(1):15-9.

  During the past 8 years, changes in the prevalence and spread of different epidemic methicillin-resistant Staphylococcus aureus (MRSA) have been observed in central Europe, with the emergence of newDuring the past 8 years, changes in the prevalence and spread of different epidemic methicillin-resistant Staphylococcus aureus (MRSA) have been observed in central Europe, with the emergence of new strains possessing fewer resistance characters. This has also been demonstrated at the level of particular hospitals. Since variation in agr specificity type has been proposed as a possible reason for population dynamics in Staphylococcus aureus, the agr specificity groups of different epidemic MRSA strains were investigated by PCR using agr group-specific primers. Four of the "old" as well as two "new" epidemic strains exhibited agr specificity group I. One group of epidemic MRSA strains, which has been observed since the beginning of the 1990s, exhibited the agr specificity group II. Sequencing the variable part ( agrB-D-C) of the agr locus revealed only six relevant nucleotide changes within this region, with three of them modifying the Shine-Dalgarno sequence region of agrC. On the basis of the results obtained, it is proposed that the dynamics observed in the population of MRSA in Germany is not due to different agr group specificities in "old" and "new" epidemic clones.

• The newly described msrC gene is not equally distributed among all isolates of Enterococcus faecium.

  Authors: G Werner, B Hildebrandt, W Witte

  Antimicrobial agents and chemotherapy. 01/2002; 45(12):3672-3.

• Aminoglycoside-streptothricin resistance gene cluster aadE-sat4-aphA-3 disseminated among multiresistant isolates of Enterococcus faecium.

  Authors: G Werner, B Hildebrandt, W Witte

  Antimicrobial agents and chemotherapy. 12/2001; 45(11):3267-9.

  Seventy-two Enterococcus faecium isolates of different origins highly resistant to nourseothricin and streptomycin were studied. Sequencing of a genomic fragment from two isolates identified a geneSeventy-two Enterococcus faecium isolates of different origins highly resistant to nourseothricin and streptomycin were studied. Sequencing of a genomic fragment from two isolates identified a gene cluster, aadE-sat4-aphA-3, which has been isolated recently in staphylococci and Campylobacter coli. Patterns of digested PCR products of aadE-sat4-aphA-3 were identical for all isolates.

• Methicillin-resistant, quinupristin-dalfopristin-resistant Staphylococcus aureus with reduced sensitivity to glycopeptides.

  Authors: G Werner, C Cuny, F J Schmitz, W Witte

  Journal of clinical microbiology. 10/2001; 39(10):3586-90.

  Of 3,052 Staphylococcus aureus strains collected by the European SENTRY surveillance study, 35 were found to be nonsusceptible to quinupristin-dalfopristin (MIC of > or =2 mg/liter). These isolatesOf 3,052 Staphylococcus aureus strains collected by the European SENTRY surveillance study, 35 were found to be nonsusceptible to quinupristin-dalfopristin (MIC of > or =2 mg/liter). These isolates originated from four hospitals in France and one in Spain. In isolates from two Parisian hospitals exhibiting the same SmaI macrorestriction pattern, streptogramin resistance was based on vatA and vgbA. One isolate from a hospital in Lyon and 22 from a hospital in Lille were of the vatB vgaB streptogramin A resistance genotype and possessed ermA and/or ermC. As deduced from the loss of either streptogramin A or streptogramin B resistance determinants in particular isolates, resistance to quinupristin-dalfopristin requires mechanisms conferring resistance to both compounds. The SmaI macrorestriction patterns of strains from hospitals in Lille and Lyon were different; however, similarity analysis suggested a relatedness of 20 methicillin-resistant S. aureus strains from the Lille hospital, a finding confirmed by PCR typing based on three different genomic polymorphisms. These groups of isolates were found to be hetero-glycopeptide-intermediate susceptible S. aureus. Information about the failure of glycopeptide chemotherapy has not been available.

• Subtyping of MRSA isolates belonging to a widely disseminated clonal group by polymorphism of the dru sequences in mec-associated DNA.

  Authors: W Witte, G Werner, C Cuny

  International journal of medical microbiology : IJMM. 05/2001; 291(1):57-62.

  During the past 7 years the "Berlin epidemic MRSA" has spread throughout whole Germany. SmaI macrorestriction patterns of this clonal group are rather stable as are the length polymorphisms at the 3'During the past 7 years the "Berlin epidemic MRSA" has spread throughout whole Germany. SmaI macrorestriction patterns of this clonal group are rather stable as are the length polymorphisms at the 3' end of the coagulase gene and the x-region of spa. However, the dru region (direct repeat units) of mec-associated DNA exhibits a length polymorphism due to deletion of one or more direct repeat units. Five different subclones could be discriminated by dru region length polymorphism. Location of deletions and of a few point mutations allow a delineation of these subclones.

• Enterococci. Habitats, infections, virulence factors, resistances to antibiotics, transfer of resistance determinants.

  Authors: I Klare, G Werner, W Witte

  Contributions to microbiology. 02/2001; 8:108-22.

• Linkage of determinants for streptogramin A, macrolide-lincosamide-streptogramin B, and chloramphenicol resistance on a conjugative plasmid in Enterococcus faecium and dissemination of this cluster among streptogramin-resistant enterococci.

  Authors: G Werner, B Hildebrandt, I Klare, W Witte

  International journal of medical microbiology : IJMM. 11/2000; 290(6):543-8.

  A new streptogramin A resistance gene, satG (= vatE), has been recently identified in Enterococcus faecium UW1965 (Werner and Witte 1999. Antimicrob. Agents Chemother. 43: 1813-1814). FurtherA new streptogramin A resistance gene, satG (= vatE), has been recently identified in Enterococcus faecium UW1965 (Werner and Witte 1999. Antimicrob. Agents Chemother. 43: 1813-1814). Further sequence analysis of this plasmid revealed that vatE is in a cluster together with other resistance genes. The identified ORFs were nearly identical with the already known genes ermB and cat. The ermB fragment exhibited more than 99% identity with a resistance region from the streptococcal plasmid pIP501, whereas the cat fragment also contained a truncated rep gene homologue with more than 99% identity to sequences in small staphylococcal plasmids. The cat-rep and the ermB-vatE segments were linked by an IS1216V insertion sequence widely distributed among enterococci. PCR analysis of additional 76 streptogramin-resistant isolates possessing vatE and ermB revealed a linkage of both genes in 45 isolates (59%); 15 of them with a gene arrangement, cat-repU-IS1216V-ermB-vatE, identical to the reference strain UW1965. An identical linkage of IS1216V-ermB-vatE was found among isolates from poultry manure, poultry meat, stool samples of humans, and hospital patients indicating a possible spread of the resistance gene cluster via the food chain to humans.

• Antibiotics in animal feed.

  Authors: W Witte, H Tschäpe, I Klare, G Werner

  Acta veterinaria Scandinavica. Supplementum. 02/2000; 93:37-44; discussion 44-5.

• Quinupristin/dalfopristin-resistant enterococci of the satA (vatD) and satG (vatE) genotypes from different ecological origins in Germany.

  Authors: G Werner, I Klare, H Heier, K H Hinz, G Böhme, M Wendt, W Witte

  Microbial drug resistance (Larchmont, N.Y.). 02/2000; 6(1):37-47.

  The semisynthetic streptogramin combination quinupristin/dalfopristin (Synercid) is a promising alternative for treatment of infections due to multiply resistant gram-positive bacteria includingThe semisynthetic streptogramin combination quinupristin/dalfopristin (Synercid) is a promising alternative for treatment of infections due to multiply resistant gram-positive bacteria including vancomycin-resistant Enterococcus faecium. Resistance is mediated by acetyltransferases SatA (VatD) or SatG (VatE). Recent papers have indicated a possible link between the use of the streptogramin virginiamycin S/M as a feed additive in commercial animal husbandry and a selection of quinupristin/dalfopristin-resistant E. faecium (QDRE). We screened manure samples from two different turkey farms and from six different pig farms (using virginiamycin), samples from a sewage water treatment plant, 24 broiler carcasses, 10 pork samples, and 200 stool samples of nonhospitalized humans for QDRE. Our strain culture collection of hospital E. faecium isolates from the last 2 years was also reviewed for QDRE. All manure and sewage samples were positive for QDRE, as well as 11 from broiler carcasses (46%), 1 from pork (10%), and 28 from human stool specimens (14%). Thirty-six hospital isolates of E. faecium exhibited resistance to quinupristin/dalfopristin. In 141 QDRE of different origin satA (vatD) and satG (vatE) genes were detected (seven isolates from humans with an unknown resistance mechanism). Streptogramin resistance determinants were tansferable in filtermating experiments for 5 of 10 satA (vatD) and 9 of 22 satG (vatE) isolates. Different EcoRI patterns of satG (vatE) plasmids and corresponding hybridizations of the satG (vatE) gene indicated nonhomologous resistance plasmids in isolates of different origin. The results of this study indicate a common gene pool for streptogramin resistance in E. faecium of different ecological origin. A selection of QDRE using the streptogramin virginiamycin S/M as a feed additive and a spread of the resistance via the food chain to humans is probable.

• Large conjugative vanA plasmids in vancomycin-resistant Enterococcus faecium.

  Authors: G Werner, I Klare, W Witte

  Journal of clinical microbiology. 08/1999; 37(7):2383-4.

• Survey of antibiotic resistance among enterococci in North Rhine-Westphalia, Germany.

  Authors: R R Reinert, G Conrads, J J Schlaeger, G Werner, W Witte, R Lütticken, I Klare

  Journal of clinical microbiology. 06/1999; 37(5):1638-41.

  A surveillance study on antibiotic resistance of enterococcal isolates (n = 730) was carried out in North Rhine-Westphalia, Germany, in 1997. Resistance rates to ampicillin (7.4%), high-levelA surveillance study on antibiotic resistance of enterococcal isolates (n = 730) was carried out in North Rhine-Westphalia, Germany, in 1997. Resistance rates to ampicillin (7.4%), high-level gentamicin (15.0%), high-level streptomycin (27.9%), ciprofloxacin (37.9%), vancomycin (1.5%), and teicoplanin (1.5%) were determined. All vancomycin-resistant enterococci (VRE) carried the vanA gene. SmaI and ApaI macrorestriction patterns indicated an intra- and interhospital spread of VRE.

• Selective pressure by antibiotics as feed additives.

  Authors: W Witte, I Klare, G Werner

  Infection. 02/1999; 27 Suppl 2:S35-8.

  Antibacterial substances are used in considerable amounts as growth promoters in animal husbandry. There are, however, incalculable risks for human health resulting from the use of particular feedAntibacterial substances are used in considerable amounts as growth promoters in animal husbandry. There are, however, incalculable risks for human health resulting from the use of particular feed additives. Even 30 years ago the detection of transferable antibiotic resistance in Enterobacteriaceae led to the demand that antibiotics used in human chemotherapy, or for which cross-resistance against human therapeutics has been demonstrated, should be prohibited as growth promoters. The application of molecular methods to typing and characterization of bacteria and their resistance genes has provided more concise evidence for the transfer of antibiotic resistance among animal husbandry and humans as to resistance to glycopeptides (vanA gene cluster) and to streptogramins (satA).

• Association between quinupristin/dalfopristin resistance in glycopeptide-resistant Enterococcus faecium and the use of additives in animal feed.

  Authors: G Werner, I Klare, W Witte

  European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 07/1998; 17(6):401-2.