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      The Animal-foods-environment interface of Klebsiella pneumoniae in Germany: an observational study on pathogenicity, resistance development and the current situation

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          Abstract

          Klebsiella ( K.)  pneumoniae as a multi-drug resistant (MDR) pathogen is an emerging challenge for clinicians worldwide. Virulence factors are capsular antigens, adherence factors, the O-lipopolysaccharide, and siderophores promoting infectivity. Mechanisms of antimicrobial resistance are inactivation of compounds via enzymes, change of membrane permeability, and alteration of the target site of the antimicrobial compound. In addition to environmental resistance, K. pneumoniae can survive increasing concentrations of disinfectants, if exposed. This review describes the temporal and spatial distribution of  K. pneumoniae in the past decades in Germany, with emphases on the development of resistance in the non-human columns of the One-Health concept. In general, K. pneumoniae is a neglected pathogen in veterinary and environmental health, and the risk of human infection concerning animal contact and food consumption is barely investigated. Few reports exist (n = 26) on antibiotic resistance of isolates from non-human origin. Multi-drug resistance and extended-spectrum β-lactamase (MDR-ESBL) strains also resistant to carbapenems and antibiotics of the ß-lactam group harbor  blaCTX-M,  blaOXA,  blaTEM,  blaSHV,  blaCMY, and PMQR have been found in animals, foods, and the environment. Colistin resistant strains carrying the  mcr-1 gene were detected in wastewater. The blaCTX-M-15 and  blaOXA-48 genes are the most frequently identified AMR genes in isolates of humans and were also the most predominant ESBL-genes in samples collected from animal hosts. Several aspects of the molecular epidemiology and resistance development of  K. pneumoniae in farm animal populations, wildlife, and foods need intensive research. Environmental health has to be integrated into national research plans, as a lack of data is apparent. Increasing awareness of the fact that non-human sources can act as a reservoir for this pathogen has to be raised.

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          Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

          The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.
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            Emergence of OXA-48 carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in dogs.

            To evaluate the possible occurrence of carbapenemase-producing Escherichia coli and Klebsiella spp. strains in domestic animals. Veterinary clinical E. coli (n = 1175) and Klebsiella spp. (n = 136) isolates consecutively collected from livestock and companion animals in Germany from June 2012 to October 2012 were screened for their susceptibility to carbapenems using the agar disc diffusion test. Carbapenemase genes were characterized by PCR and sequencing; conjugation assays were performed. Carbapenemase-positive isolates were assigned to phylogenetic lineages by multilocus sequence typing and the clonal relatedness was determined using macrorestriction analysis and subsequent PFGE. Carbapenem non-susceptible isolates of Klebsiella pneumoniae (n = 5) and E. coli (n = 3) were obtained from six dogs hospitalized in a single veterinary clinic in Hessia, Germany, partly at the same time and consecutively over the study period. All isolates harboured carbapenemase gene blaOXA-48 located within Tn1999.2 transposons on conjugative ~60 kb plasmids. The K. pneumoniae isolates belonged to sequence type ST15, pulsotype 1, and coexpressed CTX-M-15, SHV-28, OXA-1 and TEM-1. Two E. coli isolates were assigned to ST1196 and pulsotype 2 and coproduced CMY-2, SHV-12 and TEM-1, while the third E. coli isolate was of ST1431 (pulsotype 3), and possessed blaCTX-M-1, blaOXA-2 and blaTEM-1. This is the first known report of OXA-48-producing bacteria from companion animals. The clonal nature of the K. pneumoniae and two E. coli isolates suggests a nosocomial dissemination rather than repeated introduction by individual patients into the clinic.
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              Colistin resistance in Klebsiella pneumoniae.

              Increasing use of colistin for multidrug-resistant Gram-negative bacterial infections has led to the emergence of colistin resistance in Klebsiella pneumoniae in several countries worldwide, including Europe (especially Greece), and colistin resistance rates are continually increasing. Heteroresistance rates, which were significantly higher than resistance rates, were found to be important. Although the mechanism underlying resistance is unclear, it has been suggested that it is related to lipopolysaccharide modification via diverse routes. Several factors have been reported as being associated with colistin resistance, with improper use and patient-to-patient transmission being most often cited. Total infections and infection-related mortality from colistin-resistant K. pneumoniae are high, but currently there are no established treatment regimens. However, several combination regimens that are mainly colistin-based have been found to be successful for treating such infections.
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                Author and article information

                Contributors
                gamal.wareth@fli.de
                heinrich.neubauer@fli.de
                Journal
                Vet Res
                Vet Res
                Veterinary Research
                BioMed Central (London )
                0928-4249
                1297-9716
                8 February 2021
                8 February 2021
                2021
                : 52
                : 16
                Affiliations
                [1 ]GRID grid.417834.d, Friedrich-Loeffler-Institut, Institute of Bacterial Infections and Zoonoses, ; Naumburger Street 96a, 07743 Jena, Germany
                [2 ]GRID grid.411660.4, ISNI 0000 0004 0621 2741, Faculty of Veterinary Medicine, , Benha University, ; Moshtohor, Toukh, 13736 Egypt
                Author information
                http://orcid.org/0000-0001-6259-1932
                Article
                875
                10.1186/s13567-020-00875-w
                7871605
                33557913
                73d7a56e-14c5-4352-8361-87d4ef455f62
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 30 September 2020
                : 3 December 2020
                Funding
                Funded by: Projekt DEAL
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Veterinary medicine
                klebsiella pneumoniae,review,occurrence,resistance development,pathogenicity,germany

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