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Wolfgang Pfister

Other affiliations: Weimar Institute
Bio: Wolfgang Pfister is an academic researcher from University of Jena. The author has contributed to research in topics: Porphyromonas gingivalis & Periodontitis. The author has an hindex of 27, co-authored 87 publications receiving 2494 citations. Previous affiliations of Wolfgang Pfister include Weimar Institute.


Papers
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Journal ArticleDOI
TL;DR: Eleven out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable, which should be taken into consideration for the treatment of multiresistant P. aeruginosa.
Abstract: In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with beta-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

183 citations

Journal ArticleDOI
01 Jun 2009-Thorax
TL;DR: The presence of identical genotypes in UAW and LAW suggests that the UAW play a role as a reservoir of S aureus and P aeruginosa in CF, and further longitudinal analyses and comparison with invasive methods are required.
Abstract: Rationale: Lower airway (LAW) infection with Pseudomonas aeruginosa (P.a.) and Staphylococcus aureus (S.a.) is the leading cause of morbidity in Cystic Fibrosis (CF). The upper airways (UAW) were shown to be a gateway for acquisition and reservoir of opportunistic bacteria. Therefore, tools for UAW-assessment within CF-routine care require evaluation. Objectives: Aims of the study were non-invasive assessment of UAW and LAW microbial colonization and genotyping of P.a. and S.a. strains from both segments. Methods: 182 CF-patients were evaluated (age 0.4-68yrs, median 17yrs). LAW specimens were preferably sampled as expectorated sputum and UAW specimens by nasal lavage. P.a. and S.a.-isolates were typed in informative single nucleotide polymorphisms (SNPs) or by spa typing, respectively. Results: Of the typable S.a. and P.a. isolates from concomitant UAW- and LAW-positive specimens, 31 of 36 patients were carrying identical S.a. spa types and 23 of 24 patients identical P.a. SNP-genotypes in both compartments. Detection of S.a. or P.a. in LAW specimens was associated with a 15- or 88-fold higher likelihood to also identify S.a. or P.a. in a UAW specimen from the same patient. Conclusions: The presence of the same genotypes in UAW and LAW suggests a role of UAW as a reservoir of S.a. and P.a. in CF. Nasal lavage appears to be suitable for non-invasive UAW-sampling but further longitudinal analyses and comparison with invasive methods are required. While UAW bacterial colonization is typically not assessed in regular CF-care, our data challenge the need to discuss diagnostic and therapeutic standards for this airway compartment.

182 citations

Journal ArticleDOI
TL;DR: This study studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose, compared to the standard regimen of intermittent short-term infusion, results in a superior probability of target attainment as assessed by the fT>MIC value of imipenem.
Abstract: Beta-lactams are regularly administered in intermittent short-term infusions. The percentage of the dosing interval during which free drug concentrations exceed the MIC (fT(>MIC)) is the measure of drug exposure that best correlates with clinical outcome for beta-lactams. Therefore, administration by continuous infusion has gained increasing interest recently. We studied 20 critically ill patients with nosocomial pneumonia and investigated whether continuous infusion with a reduced total dose, compared to the standard regimen of intermittent short-term infusion, results in a superior probability of target attainment as assessed by the fT(>MIC) value of imipenem. In this prospective, randomized, controlled clinical study, patients received either a loading dose of 1 g/1 g imipenem and cilastatin (as a short-term infusion) at time zero, followed by 2 g/2 g imipenem-cilastatin per 24 h as a continuous infusion for 3 days (n = 10), or 1 g/1 g imipenem-cilastatin three times per day as a short-term infusion for 3 days (total daily dose, 3 g/3 g; n = 10). Imipenem concentrations in plasma were determined by using a validated liquid chromatography-tandem mass spectrometry assay. A two-compartment open model was employed for population pharmacokinetic modeling. We simulated 10,000 intensive-care-unit patients via Monte Carlo simulations for pharmacodynamic evaluation using the target 40% fT(>MIC). The probability of target attainment by MIC for intermittent infusion was robust (>90%) up to MICs of 1 to 2 mg/liter. The corresponding value for continuous infusion was 2 to 4 mg/liter. Although all 20 patients had an fT(>MIC) of 100%, 3 patients died. Patient survival was best described by employing a sepsis-related organ failure assessment score as a covariate in a logistic regression analysis. Larger clinical trials are warranted for evaluation of continuous infusions at a reduced dose of imipenem for critically ill patients.

140 citations

Journal ArticleDOI
TL;DR: It is demonstrated that Raman microspectroscopy in combination with support vector machines allow an identification of important UTI bacteria within two hours without the need of a culture step.
Abstract: Urinary tract infection (UTI) is a very common infection. Up to every second woman will experience at least one UTI episode during her lifetime. The gold standard for identifying the infectious microorganisms is the urine culture. However, culture methods are time-consuming and need at least 24 h until the results are available. Here, we report about a culture independent identification procedure by using Raman microspectroscopy in combination with innovative chemometrics. We investigated, for the first time directly, urine samples by Raman microspectroscopy on a single-cell level. In a first step, a database of eleven important UTI bacterial species, which were grown in sterile filtered urine, was built up. A support vector machine (SVM) was used to generate a statistical model, which allows a classification of this data set with an accuracy of 92% on a species level. This model was afterward used to identify infected urine samples of ten patients directly without a preceding culture step. Thereby, we we...

129 citations

Journal ArticleDOI
TL;DR: Nucleic acid techniques should replace cultivation methods as gold standard in microbiological diagnosis of progressive periodontitis and the micro-Dent(R) kit can be recommended for microbiological laboratories analysing subgingival plaque samples.
Abstract: But: Des procedures microbiologiques de laboratoire sont utilisees dans le controle de diagnostic et de traitement de formes progressives et refractaires de parodontite. Au cours des dernieres annees, des techniques se basant sur la detection des acides nucleiques ont ete elaborees. L'objectif de cette etude etait de valider le test microDent® disponible dans le commerce, permettant de detecter A. actinomycetemcomitans, P. gingivalis, P. intermedia, B. forsythus et T denticola. Methodes: 122 echantillons de plaque, preleves au niveau de poches parodontales de profondeur variable chez 33 patients atteints de parodontite severe et chez 15 sujets au parodonte sain, ont ete analyses par culture et au moyen du kit microDent®. Resultats: La methode de culture et le test base sur les acides nucleiques ont tous deux revele une correlation positive entre la profondeur de poche et la frequence et la quantite d'especes parodonto-pathogeniques. T denticola n'a ete detecte que dans les poches > 4 mm chez les patients atteints de parodontite. La comparaison des deux methodes a montre que le kit microDent® detectait a la fois P. gingivalis et B. forsythus plus souvent que la methode de culture. Conclusions: Les techniques de l'acide nucleique devraient remplacer les methodes de culture et devenir la reference en matiere de diagnostic microbiologique des parodontites progressives. Le kit microDent® peut etre recommande aux laboratoires microbiologiques qui analysent des echantillons de plaque sous-gingivale.

114 citations


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01 Jan 2016
TL;DR: The modern applied statistics with s is universally compatible with any devices to read, and is available in the digital library an online access to it is set as public so you can download it instantly.
Abstract: Thank you very much for downloading modern applied statistics with s. As you may know, people have search hundreds times for their favorite readings like this modern applied statistics with s, but end up in harmful downloads. Rather than reading a good book with a cup of coffee in the afternoon, instead they cope with some harmful virus inside their laptop. modern applied statistics with s is available in our digital library an online access to it is set as public so you can download it instantly. Our digital library saves in multiple countries, allowing you to get the most less latency time to download any of our books like this one. Kindly say, the modern applied statistics with s is universally compatible with any devices to read.

5,249 citations

Journal ArticleDOI
TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012 and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery.
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

2,853 citations

Journal ArticleDOI
TL;DR: These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia.
Abstract: It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

2,359 citations

Journal ArticleDOI
28 Aug 2014
TL;DR: In this review the factors that have been linked to the waxing of bacterial resistance are addressed and profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated.
Abstract: Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed.

1,467 citations

Journal ArticleDOI
TL;DR: This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps, with particular focus on AcrAB-TolC and Mex pumps.
Abstract: The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

1,016 citations