W V Kern

Universitätsklinikum Freiburg, Freiburg an der Elbe, Lower Saxony, Germany

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Publications (257)834.79 Total impact

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    ABSTRACT: In all European countries, hospital-acquired infections caused by Gram-negative multidrug-resistant microorganisms (GN-MDRO) are a major health threat, as these pathogens cannot be adequately treated anymore, or the start of effective antibiotic treatment is delayed. The efforts to limit the selection and spread of GN-MDRO remains a problem in cross-border healthcare, as the national guidelines on hygiene standards applicable for patients colonized or infected with GN-MDRO in hospitals are not harmonized between European countries. In order to point out the similarities and differences in the national guidelines of Germany and The Netherlands regarding GN-MDRO, guidelines were compared and an expert workshop was organized by the INTERREG IVa project EurSafety Health-net. Both guidelines divide the Gram-negative organisms into subgroups based on bacterial species and antibiotic susceptibility patterns in order to define multidrug-resistant variants of these bacteria. However, the Dutch guideline defines that GN-MDRO Enterobacteriaceae requires testing for certain mechanisms causing antibiotic resistance, whereas the German guideline makes use of a newly created classification scheme, based on phenotypic characterization. Besides diagnostic issues, the main difference between the Dutch and German guideline is the divergent evaluation of ESBL-producing Enterobacteriaceae. Special hygiene measures are required for all patients with ESBL-producing Enterobacteriaceae in The Netherlands, whereas the German guideline recommends special precautions only for those cases in which patients are colonized or infected with strains showing co-resistance to ciprofloxacin ("3MRGN"). The usage of consistent terminology and harmonized diagnostic procedures would improve the possibilities for infection prevention, treatment and patient safety. Prevention of severe non-treatable infections and outbreaks due to MDRO, caused by an increased population seeking medical treatment abroad together with an increased number of highly susceptible individuals demands gathering of regional data, and data comparable between the two sides of the Dutch-German border. The necessity to cooperate multidisciplinary and across borders is required to prevent a post-antibiotic era - in which common infections and minor injuries may lead to death.
    12/2015; 4(1):7. DOI:10.1186/s13756-015-0047-6
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    ABSTRACT: α-Defensins produced by neutrophils are important effector molecules of the innate immune system. In addition to their microbicidal effects, α-defensins have the ability to neutralize bacterial toxins. Panton-Valentine leukocidin (PVL) is the hallmark of community-acquired methicillin-resistant Staphylococcus aureus. S. aureus that produce PVL are responsible for severe diseases, including necrotizing pneumonia. Polymorphonuclear neutrophils are the target cells of PVL action. The goal of this study was to elucidate the effect of a group of α-defensins known as the human neutrophil peptides (HNPs) on the interactions between LukS-PV and LukF-PV, which compose PVL, and human PMNs. We observed that HNPs bound to both subunits of PVL and significantly decreased PVL pore formation in PMNs, with a maximum inhibition of 27%. When various HNP molecules were tested individually under the same conditions, we observed that HNP3, but not HNP1 or 2, decreased pore formation. Similarly, HNP3 significantly decreased PVL-induced PMN lysis, with a maximum inhibition of 31%. Interestingly, HNPs did not affect LukS-PV LukF-PV oligomerization, LukS-PV LukF-PV binding to PMNs or calcium influx induced by PVL in PMNs. Our results suggest that HNP3 partially protects neutrophils against PVL by interfering with the conformational changes of PVL required to form a functional pore. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Letters in Applied Microbiology 05/2015; DOI:10.1111/lam.12438 · 1.75 Impact Factor
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    ABSTRACT: Postexposure prophylaxis with antiinfective medication or immunizations are common problems in daily care of out- and inpatients in Germany. We discuss the most relevant situations in adult patients, other populations (neonates, children) are not considered. © Georg Thieme Verlag KG Stuttgart · New York.
    DMW - Deutsche Medizinische Wochenschrift 04/2015; 140(7):485-488. DOI:10.1055/s-0041-101188 · 0.55 Impact Factor
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    ABSTRACT: The detection of living microorganisms in the blood of a patient is of major diagnostic and prognostic importance. Blood cultures are the goldstandard in the diagnosis of BSIs (bloodstream infections). The "How to do: Blood culture collection" article provides a step-by-step approach to this method. The importance of obtaining blood cultures, indications and common pitfalls are explained in this teaching manuscript. © Georg Thieme Verlag KG Stuttgart · New York.
    DMW - Deutsche Medizinische Wochenschrift 04/2015; 140(9):666-9. DOI:10.1055/s-0041-101733 · 0.55 Impact Factor
  • Jobst Augustin, Sandra Mangiapane, Winfried V Kern
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    ABSTRACT: The aim of this study was to investigate whether the previously reported regional variation in outpatient antimicrobial use density in Germany has persisted or changed over time and has been similar for both children and adults. Antibiotic [at least 1 Anatomical Therapeutic Chemical (ATC) Code 'J01' drug] prescription prevalence data for the year 2010 were analysed for 17 regions. The overall age-standardized antibiotic prescription prevalence ranged between 25.0 and 36.6% in the different regions. Regional prescription patterns for children differed from those seen in adults. Age-specific differences in antibiotic prescription prevalence need to be considered when comparing antibiotic consumption between regions. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
    The European Journal of Public Health 03/2015; DOI:10.1093/eurpub/ckv050 · 2.46 Impact Factor
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    ABSTRACT: The consumption of antifungal agents increased over the last decade, resulting in the development of resistant organisms and causing a significant pharmaco economic burden. Antifungal drugs are widely used for the treatment of systemic fungal infections and high-risk patients, especially with severe hematological or oncological conditions. Up to date, there are no reliable and systematically reported data on the consumption of antifungal substances on a nationwide level available. The presented study gives an update to the previously published multicenter study investigating antifungal consumption in different settings from five university hospital centers in Germany from 2001 to 2003. Consumption data for systemic antifungal drugs were obtained through the hospital pharmacies for 2001-2003 and 2008-2011 regarding the medical and surgical services of five university hospital centers in Germany (A-E). Drug use densities were calculated as yearly RDDs/100 patient days. These calculations were performed for the surgical and medical services, and independently for surgical and medical ICUs, as well as for the hematology-oncology services. We report an increased utilization of systemic antifungal drugs in both study periods. The mean drug use density (mean value of all 5 hospitals) in the medical services increased by 24 % between 2001 and 2003. In 2011, this value was 37 % above the level from 2001 (12.4 RDD/100 patient days in 2001, 15.4 RDD/100 patient days in 2003, 17.0 RDD/100 patient days in 2011). The 4-year average drug use density (2008-2011) of medical services ranged between 11.6 RDD/100 patient days (hospital E) and 23.8 RDD/100 patient days (hospital A). Drug use densities were in medical intensive care units 29.4 RDD/100 patient days and hematology-oncology services 49.9 RDD/100 patient days. Despite the variability of the prescribing patterns between the tertiary hospitals, the presented pharmaco-epidemiological data are a cornerstone for the initiation and implementation of effective antifungal stewardship programmes and might serve as important benchmarking information for other hospitals with similar structures and baseline settings.
    Infection 02/2015; DOI:10.1007/s15010-015-0742-5 · 2.86 Impact Factor
  • DMW - Deutsche Medizinische Wochenschrift 02/2015; 140(3):172-176. DOI:10.1055/s-0041-100105 · 0.55 Impact Factor
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    ABSTRACT: Antimicrobial peptides are multifunctional effector molecules of innate immunity. In this study we investigated whether endothelial cells actively contribute to innate defense mechanisms by expression of antimicrobial peptides. We therefore stimulated human umbilical vein endothelial cells (HUVEC) with inflammatory cytokines, Th17 cytokines, heat-inactivated bacteria, bacterial conditioned medium (BCM) of Staphylococcus aureus and Streptococcus sanguinis, and lipoteichoic acid (LTA). Stimulation with single cytokines induced discrete expression of human β-defensin 3 (hBD3) by IFN-γ or IL-1β and of ribonuclease 7 (RNase7) by TNFα without any effects on LL-37 gene expression. Stronger hBD3 and RNase7 induction was observed after combined stimulation with IL-1β, TNF-α and IFN-γ and was confirmed by high hBD3 and RNase7 peptide levels in cell culture supernatants. In contrast, Th17 cytokines or stimulation with LTA did not result in AMP production. Moreover, only BCM of an invasive S. aureus bacteremia isolate induced hBD3 in HUVEC. We conclude that endothelial cells actively contribute to prevent dissemination of pathogens at the blood-tissue-barrier by production of AMPs that exhibit microbicidal and immunomodulatory functions. Further investigations should focus on tissue-specific AMP induction in different endothelial cell types, on pathogen-specific induction patterns and potentially involved pattern-recognition receptors of endothelial cells.
    Microbes and Infection 01/2015; 17(5). DOI:10.1016/j.micinf.2015.01.005 · 2.73 Impact Factor
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    ABSTRACT: We surveyed European medical schools regarding teaching of prudent antibiotic prescribing in the undergraduate curriculum. We performed a cross-sectional survey in 13 European countries (Belgium, Croatia, Denmark, France, Germany, Italy, Netherlands, Norway, Serbia, Slovenia, Spain, Switzerland, United Kingdom) in 2013. Proportional sampling was used, resulting in the selection of two to four medical schools per country. A standardized questionnaire based on literature review and validated by a panel of experts was sent to lecturers in infectious diseases, medical microbiology and clinical pharmacology. In-depth interviews were conducted with four lecturers. Thirty-five of 37 medical schools were included in the study. Prudent antibiotic use principles were taught in all but one medical school, but only four of 13 countries had a national programme. Interactive teaching formats were used less frequently than passive formats. The teaching was mandatory for 53% of the courses and started before clinical training in 71%. We observed wide variations in exposure of students to important principles of prudent antibiotic use among countries and within the same country. Some major principles were poorly covered (e.g. reassessment and duration of antibiotic therapy, communication skills). Whereas 77% of the respondents fully agreed that the teaching of these principles should be prioritized, lack of time, mainly due to rigid curriculum policies, was the main reported barrier to implementation. Given the study design, these are probably optimistic results. Teaching of prudent antibiotic prescribing principles should be improved. National and European programmes for development of specific learning outcomes or competencies are urgently needed. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Clinical Microbiology and Infection 11/2014; 21(4). DOI:10.1016/j.cmi.2014.11.015 · 5.20 Impact Factor
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    ABSTRACT: Prescription of third-generation cephalosporins and fluoroquinolones has been linked to an increasing incidence of gram-negative bacteria producing extended-spectrum beta-lactamases, methicillin-resistant Staphylococcus aureus and nosocomial infection with Clostridium difficile. Antibiotic stewardship (ABS) programmes offer evidence-based tools to control antibiotic prescription rates and thereby influence the incidence of nosocomial infection and contain the development of multidrug-resistant bacteria, but there is limited experience with such programmes at community hospitals.
    Infection 10/2014; DOI:10.1007/s15010-014-0693-2 · 2.86 Impact Factor
  • DMW - Deutsche Medizinische Wochenschrift 10/2014; 139(40):1999-2002. DOI:10.1055/s-0034-1387287 · 0.55 Impact Factor
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    ABSTRACT: GERMAP started in 2005 in order to strengthen the interdisciplinary cooperation between human and veterinary medicine. The editors of GERMAP are the Federal Office of Consumer Protection and Food Safety, the Paul-Ehrlich-Society for Chemotherapie e. V. and the Division of Infectious Diseases, University Hospital Freiburg. Three reports (in German) have been published until now, GERMAP 2008, GERMAP 2010, GERMAP 2012 (an English version of GERMAP 2012 will be available at the end of 2014). GERMAP reports a full account of national data on the use of antimicrobials and the spread and development of antimicrobial resistance in human as well as veterinary medicine. Each report contains an extensive amount of information about the most important trends and besides deals with varying current topics on the development and spread of antimicrobial resistance. The two selected examples below serve to illustrate this.
    The 3rd International conference on Responsible Use of Antibiotics in Animals, Amsterdam; 09/2014
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    ABSTRACT: Early initiation of antimicrobial treatment for acute infection is an important task in the emergency department (ED) with a likely impact on the hospital-wide antibiotic use pattern. We implemented an antibiotic stewardship (ABS) programme focused on non-trauma emergency patients at a large university hospital centre targeting broad-spectrum cephalosporin and fluoroquinolone use.
    Emergency Medicine Journal 09/2014; DOI:10.1136/emermed-2014-204067 · 1.78 Impact Factor
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    ABSTRACT: Objectives: Staphylococcus aureus initiates cardiac device-related infection (CDI) by binding of fibronectin binding protein A (FnBPA) to the device's surface. In FnBPA, specific "binding enhancing" amino acid alterations are associated with CDI. However, no study has investigated whether these mutations also occur in geographically different regions and whether they arise during infection or are inherent properties of the infecting isolate. Methods: We analysed bacterial isolates from 34 patients with S. aureus bacteraemia and implanted cardiac devices for association with CDI, FnBPA sequence, classification into a clonal complex (CC), and binding to fibronectin (Fn). Results: We confirmed that amino acid alterations at positions 652, 782, and 786 in FnBPA were associated with CDI (p = 0.005). Furthermore, CC15 and CC45 isolates were associated with CDI (p = 0.004). All isolates within a CC exhibited a characteristic mutation pattern, with major changes occurring in CC45 including a duplication of D1 and an altered immunogenic epitope in the D3 repeat. Isolates harbouring the "binding enhancing" mutations showed a slightly increased Fn binding capability, whereas Fn binding was decreased in CC45 isolates, according to a microtiter plate assay. Conclusions: FnBPA sequence variations are lineage specific and display inherent properties of the infecting isolate. Sequence analysis of FnBPA, as well as the bacterial genotype, may be used to predict the risk for device-related infection.
    Journal of Infection 09/2014; 70(2). DOI:10.1016/j.jinf.2014.09.005 · 4.02 Impact Factor
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    ABSTRACT: Efflux is an important mechanism of bacterial multidrug resistance (MDR), and the inhibition of MDR pumps by efflux pump inhibitors (EPIs) could be a promising strategy to overcome MDR. 1-(1-naphthylmethyl)-piperazine (NMP) and phenylalanine-arginine-β-naphthylamide (PAβN) are model EPIs with activity in various gram-negative bacteria expressing AcrB, the major efflux pump of Escherichia coli, or similar homologous pumps of the resistance-nodulation-cell division class. The aim of the present study was to generate E. coli AcrB mutants resistant to the inhibitory action of the two model EPIs and to identify putative EPI target residues in order to better understand mechanisms of pump inhibition. Using an in vitro random mutagenesis approach focusing on the periplasmic domain of AcrB, we identified the G141D/N282Y double mutation that substantially compromised the synergistic activity of NMP with linezolid, was associated with similar intracellular linezolid concentrations in the presence and absence of NMP, and did not impair the intrinsic MIC of various pump substrates and dye accumulation. We propose that these mutations near the outer face of the distal substrate binding pocket reduce NMP trapping. Other residues found to be relevant for efflux inhibition by NMP were G288 and A279, but mutations at these sites also changed the susceptibility to several pump substrates. Unlike with NMP, we were unable to generate AcrB periplasmic domain mutants with resistance or partial resistance to the EPI activity of PAβN which is consistent with mode of actions of PAβN differing from those of NMP.
    Antimicrobial Agents and Chemotherapy 09/2014; 58(11). DOI:10.1128/AAC.03775-14 · 4.45 Impact Factor
  • Evelina Tacconelli, Winfried V Kern
    The Lancet Infectious Diseases 06/2014; 14(8). DOI:10.1016/S1473-3099(14)70798-4 · 19.45 Impact Factor
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    ABSTRACT: Purpose Bacteremia with Staphylococcus aureus (SAB) is a serious clinical condition and is associated with a high mortality, ranging from 20 to 40 %. Different trials from tertiary referral hospitals demonstrate that infectious disease consultation and adherence to standard of care indicators reduce the high mortality. Data from <250-bed general hospitals are lacking in this context. Methods Patient cases at a community 200-bed general hospital with documented SAB were retrospectively analyzed from January 2010 to March 2013 regarding defined standard of care indicators. In April 2013, an antibiotic stewardship bundle approach was implemented targeting SAB. Follow-up was available until December 2013. Adherence to the different components of the bundle was analyzed. Results There were 64 cases of SAB reported. After exclusion of five cases, 39 cases were included in the pre-intervention period and 20 patients in the post-intervention period. Mean average bundle adherence increased from a baseline score of 0.8–3.7 (p < 0.001) in the post-intervention period, whereas in-hospital mortality decreased significantly (44 vs. 10 %, p < 0.001) despite or even because the absolute number of detected cases of SAB increased substantially after the intervention was initiated. Conclusion Although we were unable to identify whether the bundle, one of its components, or procedural improvements are responsible for the success of the intervention, our study indicates that the applied approach is feasible and is accompanied by a significant reduction of in-hospital mortality in the secondary care setting. The intervention may serve as a model for other hospitals with similar structures and baseline situations.
    Infection 06/2014; 42(4). DOI:10.1007/s15010-014-0633-1 · 2.86 Impact Factor
  • Journal of Infection 05/2014; DOI:10.1016/j.jinf.2014.05.007 · 4.02 Impact Factor

Publication Stats

5k Citations
834.79 Total Impact Points

Institutions

  • 2003–2015
    • Universitätsklinikum Freiburg
      • • Center for Chronic Immunodeficiency (CCI)
      • • Division of Infectious Diseases
      • • Department of Environmental Health Sciences
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2002–2015
    • University of Freiburg
      • Department of Environmental Health Science
      Freiburg, Baden-Württemberg, Germany
  • 2013
    • Universitätsklinikum Jena
      • Zentrum für Infektionsmedizin und Krankenhaushygiene
      Jena, Thuringia, Germany
    • Deutsche Gesellschaft für pädiatrische Infektiologie e.V.
      Berlín, Berlin, Germany
  • 2008–2011
    • University of Cologne
      • Institute for Medical Microbiology, Immunology and Hygiene
      Köln, North Rhine-Westphalia, Germany
    • University of Zurich
      • Center for Integrative Human Physiology
      Zürich, Zurich, Switzerland
  • 2004
    • University Hospital of Lausanne
      • Service des maladies infectieuses
      Lausanne, VD, Switzerland
  • 1987–2004
    • Universität Ulm
      • • Institute of Medical Microbiology and Hygiene
      • • Clinic of Internal Medicine II
      • • Department of Internal Medicine
      Ulm, Baden-Württemberg, Germany
  • 1998–2000
    • Tufts University
      • Center for Adaptation Genetics and Drug Resistance
      Boston, GA, United States
  • 1997
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 1996
    • Queen's University
      • Department of Oncology
      Kingston, Ontario, Canada