Christian Lanckohr

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.

Heparin-Induced Thrombocytopenia During Extracorporeal Membrane Oxygenation

HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) is an immune-mediated adverse effect of heparin therapy. Two clinical entities of HIT can be distinguished: HIT I and HIT II. HIT I is a harmless pharmacologic phenomenon associated with decreased platelet count within 24–48 h after initiation of heparinization. Unlike HIT II, it is not associated with thrombosis and does not necessitate discontinuation of heparin. In contrast, HIT II can cause both bleeding and thrombotic complications. It is the most important and most frequent drug-induced immunologic thrombocytopenia. Besides orthopedic and vascular surgery patients, patients after cardiac surgery are at highest risk of developing HIT II (1–5%). Its clinical importance is based on its strong association with venous and arterial thrombosis and thromboembolism (heparin-induced thrombocytopenia with associated thrombosis, HITT). HIT is caused by the development of an IgG antibody that recognizes multimolecular complexes of platelet factor 4 (PF4) and heparin. This so-called heparin-PF4-IgG complex leads to platelet activation and release of additional PF4 from alpha granules in platelets when bound to the platelet Fc receptor. Note that heparin forms a necessary part of the complex leading the further PF4 release. PF4 released in excess binds to heparin-like molecules on the surface of endothelial cells leading to immunemediated endothelial cell injury and heightening the risk for HITT and disseminated intravascular coagulation (DIC). The mainstay of therapy in HIT/HITT is the avoidance of further exposure to heparin in any form, avoidance of platelet transfusions and deferral of vitamin-K-antagonists until platelet recovery. Early use of alternative anticoagulants is inevitable when the indication for anticoagulation persists or in individuals with HITT. Extracorporeal membrane oxygenation (ECMO) remains a last line life-saving therapeutic option in patients suffering from

Continuous Glucose Monitoring in Patients Undergoing Extracorporeal Ventricular Assist Therapy

Background Dysregulations of blood glucose (BG) are associated with adverse outcome in critical illness; controlling BG to target appears to improve outcome. Since BG-control is challenging in daily intensive care practice BG-control remains poor especially in patients with rapidly fluctuating BG. To improve BG-control and to avoid deleterious hypoglycemia, automated online-measurement tools are advocated. We thus evaluated the point-accuracy of the subcutaneous Sentrino® Continuous Glucose Monitoring System (CGM, Medtronic Diabetes, Northridge, California) in patients undergoing extracorporeal cardiac life support (ECLS) for cardiogenic shock. Methods Management of BG was performed according to institute’s standard aiming at BG-levels between 100–145 mg/dl. CGM-values were recorded without taking measures into therapeutic account. Point-accuracy in comparison to intermittent BG-measurement by the ABL-blood-gas analyzer was determined. Results CGM (n = 25 patients) correlated significantly with ABL-values (r = 0.733, p<0.001). Mean error from standard was 15.0 mg/dl (11.9%). 44.2% of the readings were outside a 15% range around ABL-values. In one of 635 paired data-points, ABL revealed hypoglycemia (BG 32 mg/dl) whereas CGM did not show hypoglycemic values (132mg/dl). Conclusions CGM reveals minimally invasive BG-values in critically ill adults with dynamically impaired tissue perfusion. Because of potential deviations from standard, CGM-readings must be interpreted with caution in specific ICU-populations.

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.

Multiresistente Erreger – Antibiotic Stewardship

The adequate management of infections is an important task in critical care medicine which has an effect on patient outcome. As a result, the prevalence of antiinfective therapy is high in intensive care units. In the face of an unsettling development of worldwide microbial resistance, an optimization and reduction of antiinfective therapy is necessary. Antibiotic stewardship tries to improve antiinfective therapy with an interdisciplinary approach. One overall objective of antibiotic stewardship is the reduction of resistance induction in order to preserve the therapeutic efficiency of antibiotics. Intensive care units are important fields of action for antibiotic stewardship interventions. This article reviews available evidence and some practical aspects for antibiotic stewardship.