Dagmar Horn

Pathogenesis of Staphylococcus aureus necrotizing pneumonia: the role of PVL and an influenza coinfection

Only recently necrotizing pneumonia was defined as a specific disease entity that is caused by a Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus strain and is frequently preceded by an influenza infection. Necrotizing pneumonia is characterized by a sudden onset and rapid worsening of symptoms, leukopenia, airway hemorrhages, severe respiratory failure and a high mortality rate. Despite clear epidemiological data, the function of PVL in necrotizing pneumonia has been controversially discussed due to conflicting results from different disease models. Furthermore, there are many proposed mechanisms how a viral infection could facilitate and interact with a bacterial superinfection. In this review, we summarize current data from 43 clinical cases and results from various infection models on necrotizing pneumonia. We discuss the contribution of S. aureus PVL and a preceding influenza infection and present a concept of the pathogenesis of necrotizing pneumonia.

The management of hypertensive emergencies in children after stem cell transplantation

Aim of the review This work presents a short overview on the available data about drugs that are currently used to treat hypertensive emergencies in children with a focus on incidents after stem cell transplantation. It shows that the pediatric use of all hypotensive agents appears to be mainly based on personal experience of the attending physicians rather than on convincing clinical trials. Method A literature search was performed in MEDLINE, through PubMed, using the medical subject headings (MeSH) hypertensive emergencies, nifedipine, nicardipine, and children. Further articles were identified by checking cross-references of articles and books. Results Hypertensive emergencies in children after stem cell transplantation usually have a renal etiology, because of the treatment with the calcineurin inhibitors cyclosporine and tacrolimus. In these severe cases an immediate action is necessary to avoid possible appearance or exacerbation of endorgan damage. Because of their mechanism of action and a potential nephroprotective effect calcium channel blockers may be particularly suitable in cases of hypertensive emergencies. An intravenous application of nifedipine may compensate the difficulties of accurate dosing, but keeping in mind possible severe side effects and the lack of published experience its use in children is at least questionable. Nicardipine appears to be the hypotensive agent of first choice. In adults, the treatment of hypertensive emergencies with intravenous nicardipine is well-documented, but for an evaluation of safety in pediatric use, the published studies and case reports appear to be barely adequate. Conclusion The actual treatment approaches vary widely, demonstrating the lack of hard science on which current treatment of hypertensive emergencies in children is based. The hypotensive agent for the individual situation should be chosen considering the properties, side effects, the limited experiences with its use and the patient’s anamnesis.

Development of a Physiologically Based Pharmacokinetic Modelling Approach to Predict the Pharmacokinetics of Vancomycin in Critically Ill Septic Patients

Background and ObjectivesSepsis is characterised by an excessive release of inflammatory mediators substantially affecting body composition and physiology, which can be further affected by intensive care management. Consequently, drug pharmacokinetics can be substantially altered. This study aimed to extend a whole-body physiologically based pharmacokinetic (PBPK) model for healthy adults based on disease-related physiological changes of critically ill septic patients and to evaluate the accuracy of this PBPK model using vancomycin as a clinically relevant drug.MethodsThe literature was searched for relevant information on physiological changes in critically ill patients with sepsis, severe sepsis and septic shock. Consolidated information was incorporated into a validated PBPK vancomycin model for healthy adults. In addition, the model was further individualised based on patient data from a study including ten septic patients treated with intravenous vancomycin. Models were evaluated comparing predicted concentrations with observed patient concentration–time data.ResultsThe literature-based PBPK model correctly predicted pharmacokinetic changes and observed plasma concentrations especially for the distribution phase as a result of a consideration of interstitial water accumulation. Incorporation of disease-related changes improved the model prediction from 55 to 88% within a threshold of 30% variability of predicted vs. observed concentrations. In particular, the consideration of individualised creatinine clearance data, which were highly variable in this patient population, had an influence on model performance.ConclusionPBPK modelling incorporating literature data and individual patient data is able to correctly predict vancomycin pharmacokinetics in septic patients. This study therefore provides essential key parameters for further development of PBPK models and dose optimisation strategies in critically ill patients with sepsis.

[Multidrug-resistant bacteria in Germany. The impact of sources outside healthcare facilities].

BACKGROUND Currently, there is an ongoing discussion about the question whether the emergence of multidrug-resistant microorganisms (MDRO) among humans is due to transfer of these bacteria from animals. OBJECTIVES This review summarizes data on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing enterobacteria in animals and humans, and describes knowledge about transmission pathways. MATERIAL AND METHODS After a scientific literature analysis, relevant articles were identified by screening of titles and abstracts, amended by publications of infection control authorities and the respective reference lists. RESULTS MDRO are both transmitted in the nosocomial setting and are increasingly detected as sources of infection outside healthcare facilities. CONCLUSIONS Due to new transmission pathways of MDRO an inter-disciplinary approach towards prevention is necessary, involving medical, pharmaceutical and veterinary expertise.ZusammenfassungHintergrundDie Frage, ob die zunehmende Verbreitung von Erregern mit Antibiotika-Multiresistenzen (MRE) beim Menschen durch Übertragungen von Tieren erklärbar ist, wird öffentlich diskutiert.Ziel der ArbeitDiese Übersichtsarbeit trägt Daten zum Vorkommen von Methicillin-resistenten Staphylococcus aureus (MRSA) und Extended-Spectrum Beta-Lactamase (ESBL) bildenden Enterobakterien bei Mensch und Tier zusammen und beschreibt die Erkenntnisse zur zoonotischen Transmission.Material und MethodenEs wurde eine Literaturrecherche durchgeführt. Relevante Literatur wurde durch Screening von Überschriften und Abstracts identifiziert und ergänzt durch Publikationen von Infektionsschutzbehörden bzw. die dort zitierten Originalarbeiten.ErgebnisseEs zeigte sich eine Vielzahl nosokomialer Verbreitungswege von MRE sowie eine zunehmende Relevanz von außerhalb des Gesundheitswesens gelegenen Infektionsquellen.DiskussionFür eine effektive Prävention von MRE ist ein interdisziplinärer Ansatz notwendig, der sowohl die Grenzen medizinischer und pharmazeutischer Fachgebiete als auch die Grenzen zwischen Human- und Veterinärmedizin überschreitet.AbstractBackgroundCurrently, there is an ongoing discussion about the question whether the emergence of multidrug-resistant microorganisms (MDRO) among humans is due to transfer of these bacteria from animals.ObjectivesThis review summarizes data on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing enterobacteria in animals and humans, and describes knowledge about transmission pathways.Material and methodsAfter a scientific literature analysis, relevant articles were identified by screening of titles and abstracts, amended by publications of infection control authorities and the respective reference lists.ResultsMDRO are both transmitted in the nosocomial setting and are increasingly detected as sources of infection outside healthcare facilities.ConclusionsDue to new transmission pathways of MDRO an inter-disciplinary approach towards prevention is necessary, involving medical, pharmaceutical and veterinary expertise.

Antibiotika-resistente Erreger in Deutschland

BACKGROUND Currently, there is an ongoing discussion about the question whether the emergence of multidrug-resistant microorganisms (MDRO) among humans is due to transfer of these bacteria from animals. OBJECTIVES This review summarizes data on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing enterobacteria in animals and humans, and describes knowledge about transmission pathways. MATERIAL AND METHODS After a scientific literature analysis, relevant articles were identified by screening of titles and abstracts, amended by publications of infection control authorities and the respective reference lists. RESULTS MDRO are both transmitted in the nosocomial setting and are increasingly detected as sources of infection outside healthcare facilities. CONCLUSIONS Due to new transmission pathways of MDRO an inter-disciplinary approach towards prevention is necessary, involving medical, pharmaceutical and veterinary expertise.ZusammenfassungHintergrundDie Frage, ob die zunehmende Verbreitung von Erregern mit Antibiotika-Multiresistenzen (MRE) beim Menschen durch Übertragungen von Tieren erklärbar ist, wird öffentlich diskutiert.Ziel der ArbeitDiese Übersichtsarbeit trägt Daten zum Vorkommen von Methicillin-resistenten Staphylococcus aureus (MRSA) und Extended-Spectrum Beta-Lactamase (ESBL) bildenden Enterobakterien bei Mensch und Tier zusammen und beschreibt die Erkenntnisse zur zoonotischen Transmission.Material und MethodenEs wurde eine Literaturrecherche durchgeführt. Relevante Literatur wurde durch Screening von Überschriften und Abstracts identifiziert und ergänzt durch Publikationen von Infektionsschutzbehörden bzw. die dort zitierten Originalarbeiten.ErgebnisseEs zeigte sich eine Vielzahl nosokomialer Verbreitungswege von MRE sowie eine zunehmende Relevanz von außerhalb des Gesundheitswesens gelegenen Infektionsquellen.DiskussionFür eine effektive Prävention von MRE ist ein interdisziplinärer Ansatz notwendig, der sowohl die Grenzen medizinischer und pharmazeutischer Fachgebiete als auch die Grenzen zwischen Human- und Veterinärmedizin überschreitet.AbstractBackgroundCurrently, there is an ongoing discussion about the question whether the emergence of multidrug-resistant microorganisms (MDRO) among humans is due to transfer of these bacteria from animals.ObjectivesThis review summarizes data on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing enterobacteria in animals and humans, and describes knowledge about transmission pathways.Material and methodsAfter a scientific literature analysis, relevant articles were identified by screening of titles and abstracts, amended by publications of infection control authorities and the respective reference lists.ResultsMDRO are both transmitted in the nosocomial setting and are increasingly detected as sources of infection outside healthcare facilities.ConclusionsDue to new transmission pathways of MDRO an inter-disciplinary approach towards prevention is necessary, involving medical, pharmaceutical and veterinary expertise.

Antibiotika-resistente Erreger in Deutschland@@@Multidrug-resistant bacteria in Germany: Die Rolle von nicht nosokomialen Ansteckungsquellen@@@The impact of sources outside healthcare facilities

BACKGROUND Currently, there is an ongoing discussion about the question whether the emergence of multidrug-resistant microorganisms (MDRO) among humans is due to transfer of these bacteria from animals. OBJECTIVES This review summarizes data on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing enterobacteria in animals and humans, and describes knowledge about transmission pathways. MATERIAL AND METHODS After a scientific literature analysis, relevant articles were identified by screening of titles and abstracts, amended by publications of infection control authorities and the respective reference lists. RESULTS MDRO are both transmitted in the nosocomial setting and are increasingly detected as sources of infection outside healthcare facilities. CONCLUSIONS Due to new transmission pathways of MDRO an inter-disciplinary approach towards prevention is necessary, involving medical, pharmaceutical and veterinary expertise.ZusammenfassungHintergrundDie Frage, ob die zunehmende Verbreitung von Erregern mit Antibiotika-Multiresistenzen (MRE) beim Menschen durch Übertragungen von Tieren erklärbar ist, wird öffentlich diskutiert.Ziel der ArbeitDiese Übersichtsarbeit trägt Daten zum Vorkommen von Methicillin-resistenten Staphylococcus aureus (MRSA) und Extended-Spectrum Beta-Lactamase (ESBL) bildenden Enterobakterien bei Mensch und Tier zusammen und beschreibt die Erkenntnisse zur zoonotischen Transmission.Material und MethodenEs wurde eine Literaturrecherche durchgeführt. Relevante Literatur wurde durch Screening von Überschriften und Abstracts identifiziert und ergänzt durch Publikationen von Infektionsschutzbehörden bzw. die dort zitierten Originalarbeiten.ErgebnisseEs zeigte sich eine Vielzahl nosokomialer Verbreitungswege von MRE sowie eine zunehmende Relevanz von außerhalb des Gesundheitswesens gelegenen Infektionsquellen.DiskussionFür eine effektive Prävention von MRE ist ein interdisziplinärer Ansatz notwendig, der sowohl die Grenzen medizinischer und pharmazeutischer Fachgebiete als auch die Grenzen zwischen Human- und Veterinärmedizin überschreitet.AbstractBackgroundCurrently, there is an ongoing discussion about the question whether the emergence of multidrug-resistant microorganisms (MDRO) among humans is due to transfer of these bacteria from animals.ObjectivesThis review summarizes data on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing enterobacteria in animals and humans, and describes knowledge about transmission pathways.Material and methodsAfter a scientific literature analysis, relevant articles were identified by screening of titles and abstracts, amended by publications of infection control authorities and the respective reference lists.ResultsMDRO are both transmitted in the nosocomial setting and are increasingly detected as sources of infection outside healthcare facilities.ConclusionsDue to new transmission pathways of MDRO an inter-disciplinary approach towards prevention is necessary, involving medical, pharmaceutical and veterinary expertise.

Hypertensive Emergencies in Children After Stem Cell Transplantation: Care in Selecting Hypotensive Drugs

Hypertensive emergencies in children are rare, but associated with a significant risk of morbidity and mortality. These situations make an immediate, and especially a controlled reduction of blood pressure necessary. In children after stem cell transplantation hypertension is usually secondary to a renal impairment caused by the treatment with cyclosporine and tacrolimus. Due to the lack of adequate published experience with the used hypotensive drugs, and the lack of corresponding guidelines for an effective management of these situations, the actual treatment options in children only vary slightly from those in adults, and are primarily based on small retrospective clinical trials, and case reports.