Thomas Grünewald

Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care

BACKGROUND In the current epidemic of Ebola virus disease in western Africa, many aid workers have become infected. Some of these aid workers have been transferred to specialised hospitals in Europe and the USA for intensified treatment, providing the potential for unique insight into the clinical course of Ebola virus disease under optimised supportive measures in isolation units. METHODS A 38-year-old male doctor who had contracted an Ebola virus infection in Sierra Leone was airlifted to University Hospital Frankfurt, Germany, on day 5 after disease onset. Within 72 h of admission to the hospitals high-level isolation unit, the patient developed signs of severe multiorgan failure, including lungs, kidneys, and gastrointestinal tract. In addition to clinical parameters, the diagnostic work-up included radiography, ultrasound, pulse contour cardiac output technology, and microbiological and clinical chemistry analyses. Respiratory failure with pulmonary oedema and biophysical evidence of vascular leak syndrome needed mechanical ventilation. The patient received a 3 day treatment course with FX06 (MChE-F4Pharma, Vienna, Austria), a fibrin-derived peptide under clinical development for vascular leak syndrome. After FX06 administration and concurrent detection of Ebola-virus-specific antibodies and a fall in viral load, vascular leak syndrome and respiratory parameters substantially improved. We gave broad-spectrum empiric antimicrobial therapy and the patient needed intermittent renal replacement therapy. The patient fully recovered. FINDINGS This case report shows the feasibility of delivery of successful intensive care therapy to patients with Ebola virus disease under biosafety level 4 conditions. INTERPRETATION The effective treatment of vascular leakage and multiorgan failure by combination of ventilatory support, antibiotic treatment, and renal replacement therapy can sustain a patient with severe Ebola virus disease until virological remission. FX06 could potentially be a valuable agent in contribution to supportive therapy. FUNDING University Hospital of Frankfurt.

Clinical Management of Ebola Virus Disease in the United States and Europe

BACKGROUND Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. METHODS We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015. RESULTS A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renal-replacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had respiratory and renal failure, for a mortality of 18.5%. CONCLUSIONS Among the patients with EVD who were cared for in the United States or Europe, close monitoring and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support, and critical care management for respiratory and renal failure were needed; 81.5% of these patients who received this care survived.

A Single Dose of Ceftriaxone Administered 30 Minutes Before Percutaneous Endoscopic Gastrostomy Significantly Reduces Local and Systemic Infective Complications

Objective:The aim of this study was to determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG).Methods:An open prospective, randomised, multicenter study was conducted in 141 patients; 72 received ceftriaxone 1 g i.v. 30 min preintervention, and 69 received no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15-Fr gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score >3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined.Results:In no-prophylaxis patients, wound infection rates were 25% on day 4 and 26.4% on day 10, versus 10.1% (p= 0.03) and 14.5% (p= 0.10), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients: systemic infection rates were 16.7%versus 5.8% in no-prophylaxis versus prophylaxis patients (p= 0.045), and overall infection rates 38.9%versus 17.4%, respectively (p= 0.046). Pneumonia was more frequent in patients with underlying neurological disease. Antibiotic costs were the same in both groups (p= 0.792).Conclusions:Single dose ceftriaxone 1 g is an effective prophylaxis against local and systemic infection after PEG.

Schutz vor lebensbedrohenden importierten Infektionskrankheiten Strukturelle Erfordernisse bei der Behandlung von Patienten und anti-epidemische Maßnahmen

ZusammenfassungVerschiedene virusbedingte hämorrhagische Fieber (VHF), Pocken (humane Affenpocken) sowie Lungenpest erfordern besondere Maßnahmen zum Schutz des Krankenhauspersonals und anderer Personen vor Ansteckung. Kontaktpersonen müssen ermittelt und überwacht werden, um eine Ausbreitung zu verhindern. Ein im Mai 1999 veröffentlichtes Konzept zum Management und zur Kontrolle dieser lebensbedrohenden hochkontagiösen Infektionskrankheiten wurde inzwischen mit Fachöffentlichkeit und Gesundheitsbehörden diskutiert. Bei den zwischenzeitlich aufgetretenen Fällen bestätigte sich das vorgeschlagene Vorgehen : In Deutschland werden die mikrobiologische Diagnostik und Differentialdiagnostik zentral von einem Zentrum der biologischen Sicherheitsstufe BSL4 und einem entsprechenden Bestätigungslabor vorgenommen. Für Isolierung und klinische Behandlung der Patienten stehen vier Behandlungszentren zur Verfügung, ein fünftes soll im nächsten Jahr betriebsbereit sein. Die zunehmende Inanspruchnahme zeigt, dass sich die vorgesehene Schwerpunktversorgung durchsetzt. Handelsübliche Transportisolatoren sind für schwer kranke Personen nicht geeignet. Ohne deren Verwendung können Luftfahrzeuge jedoch nicht regelrecht dekontaminiert werden. Transporte sollen daher grundsätzlich auf dem Landweg erfolgen. Zur Unterstützung und Beratung der erstversorgenden Krankenhäuser und der örtlich zuständigen Amtsärzte sollen um die Behandlungszentren sog. Kompetenzzentren entstehen. Der Personal- und Platzbedarf bei der Versorgung eines an einem VHF Erkrankten in fortgeschrittenem Stadium ist höher als erwartet. Die adäquate Versorgung von Kranken in sog. Bettisolatoren ist nicht möglich. Routinelaboruntersuchungen müssen in der Behandlungseinheit erfolgen. Maßnahmen zur Verhinderung der Weiterverbreitung müssen stärker koordiniert werden. Die von uns vorgeschlagene Einteilung der Kontaktpersonen wird um eine Auflistung der empfohlenen Maßnahmen ergänzt.AbstractPatients infected with viral haemorrhagic fevers (VHF), pneumonic plague or zoonotic orthopoxvirus infections usually require intensive care and a special isolation. Contact persons must be traced and monitored. Last year our working group published a concept for the management and control of these life-threatening highly contagious diseases. Now the principles of our plan have been accepted. The development of guidelines for rapid reaction to those communicable diseases is an important task for all EU Member States. In Germany microbiological diagnosis is performed by a diagnostic centre (Biosafety-Level BSL4) and supported by a corresponding confirmation laboratory. At present four high security infectious disease units for patient care (HSIU) are available in Munich, Leipzig, Hamburg and Berlin. Another one located in Frankfurt will be functional by 2001. In addition to the HSIU a corresponding number of centres of competence shall be established in order to support and advise the hospitals initially treating the patients as well as the local public health officer. The risk categorisation for contact persons, which has been developed by our working group, has proved to be very useful in practice. Ambulances should be used for transfer of patients to the HSIU. So-called transport-isolators are not suitable for patients who are seriously ill. Air-based transport without using an isolator is a problem, since no decontamination procedure exists. As soon as the last HSIU in the Rhine Main area is working the centres of competence will be established. This will provide competent health care for VHF-patients and a convincing management for these kinds of threats to public health everywhere in Germany.

Aufgaben und Funktion der Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren für hochkontagiöse, lebensbedrohliche Erkrankungen

ZusammenfassungDie Einschleppung von Tropenkrankheiten nach Deutschland wird durch den zunehmenden Ferntourismus und durch die Globalisierung wirtschaftlicher Aktivitäten zu einem immer häufiger auftretenden Problem für das Gesundheitswesen. Die vernetzte Struktur landkreis- und teilweise länderübergreifender Kompetenzzentren für hochkontagiöse lebensbedrohliche Infektionskrankheiten hat sich bewährt und gezeigt, dass durch die Verknüpfung von öffentlichem Gesundheitsdienst (ÖGD), klinischer Versorgung, laborgestützte Spezialdiagnostik, Feuerwehr/Rettungsdienst und Krankenhaushygiene auch auf zunächst unerwartete infektiologische Situationen schnell und professionell reagiert werden kann. Mit diesen Netzwerken, die sich in der Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren (StAKoB) zusammengeschlossen haben, verfügt Deutschland derzeit über ein weltweit einzigartiges Instrument zur Behandlung hochinfektiöser, lebensbedrohlicher Infektionskrankheiten. Im vorliegenden Beitrag werden die Ziele und die Struktur der StAKoB dargestellt.AbstractThe introduction of tropical diseases into Germany is becoming a more and more frequent public health problem due to increasing long distance travel and the globalization of economic activities. A network of centers of excellence for imported, highly contagious diseases has proven efficient and shown that the linking of public health service, clinical care, laboratory-based special diagnostics, ambulance service, and hospital hygiene can react quickly and professionally in even unexpected situations in clinical infectiology. These networks joined forces in the “Permanent Working Group of the Medical Competence and Treatment Centers“ (Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren, StAKoB). Not only in Germany but also worldwide, the StAKoB is a unique system for the treatment of imported highly contagious diseases. The goals and structure of the StAKoB are presented in this article.

Staphylococcus colonization, mortality and morbidity in hemodialysis patients: 10 years of observation

Colonization with Staphylococci is widely distributed among patients with end-stage renal disease who are receiving hemodialysis (HD). In addition to more intensive care and use of artificial devices, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection has increased. Such colonization has recently been associated with a more than doubled mortality rate in HD patients. However, it is not clear whether the (presumably increasing) incidence of methicillin-sensitive Staphylococcus aureus (MSSA) colonization is associated with MRSA and/or morbidity and mortality. We therefore established a screening program in our HD population (n=156) and followed these patients over 10 years. We discovered eighty-eight MSSA-colonized patients and one MRSA-colonized patient by cross-sectional and admission-related screenings between 2000 and 2010. The morbidity and mortality of the HD patients was not related to MSSA colonization. The MSSA colonization rate decreased slightly during the 10-year observation period. We conclude that the incidence of MRSA colonization in our unit was lower compared to that reported in the literature. The reasons for this finding are complex and require further investigation. The incidence of MSSA colonization was frequent but did not impact morbidity or mortality.

Strukturelle Erfordernisse für das Management von Patienten mit hochkontagiösen, lebensbedrohlichen Erkrankungen – Update 2015

ZusammenfassungDie Versorgung von Patienten mit hochkontagiösen, lebensbedrohlichen Erkrankungen (HKLE) erfordert spezialisierte Behandlungseinrichtungen, die neben einer strikten Isolierung der Erkrankten gleichzeitig eine adäquate medizinische Betreuung ermöglichen. Das in Deutschland bestehende nationale Konzept zum Management dieser hochkontagiösen, lebensbedrohlichen Erkrankungen, das durch die Zentren des „Ständigen Arbeitskreises der Kompetenz- und Behandlungszentren für hochkontagiöse und lebensbedrohliche Erkrankungen“ (STAKOB) am Robert Koch-Institut gewährleistet wird, soll durch die vorliegende Publikation, die sich auf die rezenten Erfahrungen in der Versorgung solcher Erkrankungen bezieht, an neue und kommende Erfordernisse angepasst werden. Synergien im Sinne einer systematischen Verbesserung der Infrastrukturen und einer Bündelung von Ressourcen haben zu vergleichbaren Anstrengungen auf europäischer Ebene geführt. So hat das von den Mitgliedern des STAKOB getragene Konzept eine Vorreiterfunktion. Die hier vorliegende Aktualisierung soll der verbesserten professionellen Versorgung von Patienten mit HKLE dienen und das Risiko einer Krankheitsübertragung auf Dritte weiter minimieren.AbstractThe care of highly contagious life-threatening infectious diseases (HLID) requires specialized treatment facilities that are capable of strict isolation measures and appropriate medical treatment. The German approach to the management of these diseases, which is maintained by the Permanent Working Group of Medical Competence and Treatment Centers for Highly Contagious and Life-Threatening Diseases (STAKOB) is adjusted in the present publication with regards to recent experiences and upcoming needs. Clear synergies in using infrastructures and bundling of resources have led to similar efforts at the European level. The German concept, therefore, has a pioneering role. This update is intended to improve professional patient care and also minimize the risk of disease spread and transmission.The care of highly contagious life-threatening infectious diseases (HLID) requires specialized treatment facilities that are capable of strict isolation measures and appropriate medical treatment. The German approach to the management of these diseases, which is maintained by the Permanent Working Group of Medical Competence and Treatment Centers for Highly Contagious and Life-Threatening Diseases (STAKOB) is adjusted in the present publication with regards to recent experiences and upcoming needs. Clear synergies in using infrastructures and bundling of resources have led to similar efforts at the European level. The German concept, therefore, has a pioneering role. This update is intended to improve professional patient care and also minimize the risk of disease spread and transmission.

Was tun bei Ebolafieber-Verdacht?

Das Ausmaß des Ebola-Ausbruchs in Westafrika ist beispiellos. Und mittlerweile ist auch in Deutschland die Sorge groß, dass die Krankheit durch infizierte Personen importiert werden könnte. Bei welchen Symptomen müssen Sie an eine Ebolafieber-Infektion denken? Wie gehen Sie vor, wenn sich der Verdacht als begründet herausstellt? Regelmäßig aktualisierte Konzepte zum Umgang mit hoch ansteckenden, lebensbedrohlichen Infektionskrankheiten dienen als Grundlage für die notwendigen Maßnahmen.

Strukturelle Erfordernisse für das Management von Patienten mit hochkontagiösen, lebensbedrohlichen Erkrankungen – Update 2015@@@Structural requirements for the management of patients with highly contagious life-threatening infectious diseases: update 2015

ZusammenfassungDie Versorgung von Patienten mit hochkontagiösen, lebensbedrohlichen Erkrankungen (HKLE) erfordert spezialisierte Behandlungseinrichtungen, die neben einer strikten Isolierung der Erkrankten gleichzeitig eine adäquate medizinische Betreuung ermöglichen. Das in Deutschland bestehende nationale Konzept zum Management dieser hochkontagiösen, lebensbedrohlichen Erkrankungen, das durch die Zentren des „Ständigen Arbeitskreises der Kompetenz- und Behandlungszentren für hochkontagiöse und lebensbedrohliche Erkrankungen“ (STAKOB) am Robert Koch-Institut gewährleistet wird, soll durch die vorliegende Publikation, die sich auf die rezenten Erfahrungen in der Versorgung solcher Erkrankungen bezieht, an neue und kommende Erfordernisse angepasst werden. Synergien im Sinne einer systematischen Verbesserung der Infrastrukturen und einer Bündelung von Ressourcen haben zu vergleichbaren Anstrengungen auf europäischer Ebene geführt. So hat das von den Mitgliedern des STAKOB getragene Konzept eine Vorreiterfunktion. Die hier vorliegende Aktualisierung soll der verbesserten professionellen Versorgung von Patienten mit HKLE dienen und das Risiko einer Krankheitsübertragung auf Dritte weiter minimieren.AbstractThe care of highly contagious life-threatening infectious diseases (HLID) requires specialized treatment facilities that are capable of strict isolation measures and appropriate medical treatment. The German approach to the management of these diseases, which is maintained by the Permanent Working Group of Medical Competence and Treatment Centers for Highly Contagious and Life-Threatening Diseases (STAKOB) is adjusted in the present publication with regards to recent experiences and upcoming needs. Clear synergies in using infrastructures and bundling of resources have led to similar efforts at the European level. The German concept, therefore, has a pioneering role. This update is intended to improve professional patient care and also minimize the risk of disease spread and transmission.The care of highly contagious life-threatening infectious diseases (HLID) requires specialized treatment facilities that are capable of strict isolation measures and appropriate medical treatment. The German approach to the management of these diseases, which is maintained by the Permanent Working Group of Medical Competence and Treatment Centers for Highly Contagious and Life-Threatening Diseases (STAKOB) is adjusted in the present publication with regards to recent experiences and upcoming needs. Clear synergies in using infrastructures and bundling of resources have led to similar efforts at the European level. The German concept, therefore, has a pioneering role. This update is intended to improve professional patient care and also minimize the risk of disease spread and transmission.

Aufgaben und Funktion der Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren für hochkontagiöse, lebensbedrohliche Erkrankungen@@@The goals and structure of the Permanent Working Group of Medical Competence and Treatment Centers for highly contagious, life-threatening diseases

ZusammenfassungDie Einschleppung von Tropenkrankheiten nach Deutschland wird durch den zunehmenden Ferntourismus und durch die Globalisierung wirtschaftlicher Aktivitäten zu einem immer häufiger auftretenden Problem für das Gesundheitswesen. Die vernetzte Struktur landkreis- und teilweise länderübergreifender Kompetenzzentren für hochkontagiöse lebensbedrohliche Infektionskrankheiten hat sich bewährt und gezeigt, dass durch die Verknüpfung von öffentlichem Gesundheitsdienst (ÖGD), klinischer Versorgung, laborgestützte Spezialdiagnostik, Feuerwehr/Rettungsdienst und Krankenhaushygiene auch auf zunächst unerwartete infektiologische Situationen schnell und professionell reagiert werden kann. Mit diesen Netzwerken, die sich in der Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren (StAKoB) zusammengeschlossen haben, verfügt Deutschland derzeit über ein weltweit einzigartiges Instrument zur Behandlung hochinfektiöser, lebensbedrohlicher Infektionskrankheiten. Im vorliegenden Beitrag werden die Ziele und die Struktur der StAKoB dargestellt.AbstractThe introduction of tropical diseases into Germany is becoming a more and more frequent public health problem due to increasing long distance travel and the globalization of economic activities. A network of centers of excellence for imported, highly contagious diseases has proven efficient and shown that the linking of public health service, clinical care, laboratory-based special diagnostics, ambulance service, and hospital hygiene can react quickly and professionally in even unexpected situations in clinical infectiology. These networks joined forces in the “Permanent Working Group of the Medical Competence and Treatment Centers“ (Ständigen Arbeitsgemeinschaft der Kompetenz- und Behandlungszentren, StAKoB). Not only in Germany but also worldwide, the StAKoB is a unique system for the treatment of imported highly contagious diseases. The goals and structure of the StAKoB are presented in this article.