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      Antibiotic resistance: What is so special about multidrug-resistant Gram-negative bacteria? Translated title: Antibiotikaresistenz: Was ist so besonders an den Gram-negativen multiresistenten Bakterien?

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          Abstract

          In the past years infections caused by multidrug-resistant Gram-negative bacteria have dramatically increased in all parts of the world. This consensus paper is based on presentations, subsequent discussions and an appraisal of current literature by a panel of international experts invited by the Rudolf Schülke Stiftung, Hamburg. It deals with the epidemiology and the inherent properties of Gram-negative bacteria, elucidating the patterns of the spread of antibiotic resistance, highlighting reservoirs as well as transmission pathways and risk factors for infection, mortality, treatment and prevention options as well as the consequences of their prevalence in livestock. Following a global, One Health approach and based on the evaluation of the existing knowledge about these pathogens, this paper gives recommendations for prevention and infection control measures as well as proposals for various target groups to tackle the threats posed by Gram-negative bacteria and prevent the spread and emergence of new antibiotic resistances.

          Zusammenfassung

          In den letzten Jahren haben die durch multiresistente Gram-negative Bakterien (MRGN) verursachten Infektionen in allen Teilen der Welt dramatisch zugenommen. Der vorliegende Konsensus basiert auf Vorträgen mit sich anschließenden Diskussionen und späterer Auswertung der einschlägigen Literatur durch ein internationales Expertengremium, das von der Rudolf Schülke Stiftung, Hamburg, zu dem Meeting nach Hamburg eingeladen worden war. Im Fokus standen die Epidemiologie und die besonderen Eigenschaften Gram-negativer Bakterien, die Ausbreitung der Antibiotikaresistenz, die Reservoire, Übertragungswege und Risikofaktoren für Infektionen, die Mortalität, die Therapie und die Möglichkeiten der Prävention einschließlich der Konsequenzen des Vorkommens in der industriellen Tierhaltung. Dem One Health Ansatz folgend und basierend auf der Bewertung des Wissensstandes zu diesen Erregern werden Empfehlungen zur Prävention und Bekämpfung sowie Vorschläge für verschiedene Zielgruppen unterbreitet, um der Bedrohung durch MRGN zu begegnen, ihre Ausbreitung zu verhindern und die Entstehung neuer Antibiotikaresistenzen zu unterbinden.

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          Tackling antibiotic resistance: the environmental framework.

          Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.
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            Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.

            Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock. The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries. Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23). Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
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              Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies.

              Carbapenem-resistant Klebsiella pneumoniae is an emerging healthcare-associated pathogen. To describe the epidemiology of and clinical outcomes associated with carbapenem-resistant K. pneumoniae infection and to identify risk factors associated with mortality among patients with this type of infection. Mount Sinai Hospital, a 1,171-bed tertiary care teaching hospital in New York City. Two matched case-control studies. In the first matched case-control study, case patients with carbapenem-resistant K. pneumoniae infection were compared with control patients with carbapenem-susceptible K. pneumoniae infection. In the second case-control study, patients who survived carbapenem-resistant K. pneumoniae infection were compared with those who did not survive, to identify risk factors associated with mortality among patients with carbapenem-resistant K. pneumoniae infection. There were 99 case patients and 99 control patients identified. Carbapenem-resistant K. pneumoniae infection was independently associated with recent organ or stem-cell transplantation (P=.008), receipt of mechanical ventilation (P=.04), longer length of stay before infection (P=.01), and exposure to cephalosporins (P=.02) and carbapenems (P<.001). Case patients were more likely than control patients to die during hospitalization (48% vs 20%; P<.001) and to die from infection (38% vs 12%; P<.001). Removal of the focus of infection (ie, debridement) was independently associated with patient survival (P=.002). The timely administration of antibiotics with in vitro activity against carbapenem-resistant K. pneumoniae was not associated with patient survival. Carbapenem-resistant K. pneumoniae infection is associated with numerous healthcare-related risk factors and with high mortality. The mortality rate associated with carbapenem-resistant K. pneumoniae infection and the limited antimicrobial options for treatment of carbapenem-resistant K. pneumoniae infection highlight the need for improved detection of carbapenem-resistant K. pneumoniae infection, identification of effective preventive measures, and development of novel agents with reliable clinical efficacy against carbapenem-resistant K. pneumoniae.
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                Author and article information

                Journal
                GMS Hyg Infect Control
                GMS Hyg Infect Control
                GMS Hyg Infect Control
                GMS Hygiene and Infection Control
                German Medical Science GMS Publishing House
                2196-5226
                10 April 2017
                2017
                : 12
                : Doc05
                Affiliations
                [1 ]Institute of Hygiene and Public Health, Bonn University, Bonn, Germany
                [2 ]Tata Medical Center, Kolkata, India
                [3 ]Department of Internal Hygiene, Schleswig-Holstein University Hospital, Kiel, Germany
                [4 ]Schülke & Mayr GmbH, Norderstedt, Germany
                [5 ]Departement Environnement et Santé Publique S.E.R.E.S., Faculté de Médecine, Nancy, France
                [6 ]Institute of Medical Microbiology and Hygiene, University of Tübingen, Germany
                [7 ]Institute of Hygiene and Environmental Medicine, University Medicine Greifswald, Germany
                [8 ]School of Nursing, Columbia University, New York, USA
                [9 ]Mailman School of Public Health, Columbia University, New York, USA
                [10 ]Robert Koch Institute (RKI), Berlin, Germany
                [11 ]Hospital Hygiene, Essen University Hospital, Essen, Germany
                [12 ]Hygiene Institute, Medical University Vienna, Austria
                [13 ]Institute of Hygiene and Medical Microbiology, University of Heidelberg, Germany
                [14 ]Department of Hospital Hygiene, Stuttgart Hospital, Stuttgart, Germany
                Author notes
                *To whom correspondence should be addressed: Martin Exner, Institute of Hygiene and Public Health, Bonn University, WHO CC, Sigmund-Freud-Str. 25, 53105 Bonn, Gemany, Phone: +49 228 287 15520, E-mail: martin.exner@ 123456ukb.uni-bonn.de
                Article
                dgkh000290 Doc05 urn:nbn:de:0183-dgkh0002900
                10.3205/dgkh000290
                5388835
                28451516
                94f7897f-3ff6-431b-a2d1-3a39f4182b48
                Copyright © 2017 Exner et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

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                Categories
                Article

                multidrug-resistant gram-negative bacteria,epidemiology,surveillance,reservoirs,resistance patterns,therapy,infection control measures,biocides,disinfection,agriculture

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