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      Antimicrobial resistance of Klebsiella pneumoniae stool isolates circulating in Kenya

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          Abstract

          We sought to determine the genetic and phenotypic antimicrobial resistance (AMR) profiles of commensal Klebsiella spp. circulating in Kenya by testing human stool isolates of 87 K. pneumoniae and three K. oxytoca collected at eight locations. Over one-third of the isolates were resistant to ≥3 categories of antimicrobials and were considered multidrug-resistant (MDR). We then compared the resistance phenotype to the presence/absence of 238 AMR genes determined by a broad-spectrum microarray and PCR. Forty-six genes/gene families were identified conferring resistance to β-lactams ( ampC/ bla DHA, bla CMY/LAT, bla LEN-1, bla OKP-A/OKP-B1, bla OXA-1-like family, bla OXY-1, bla SHV, bla TEM, bla CTX-M-1 and bla CTX-M-2 families), aminoglycosides ( aac(3)-III, aac(6)-Ib, aad(A1/A2), aad(A4), aph(AI), aph3/str(A), aph6/str(B), and rmtB), macrolides ( mac(A), mac(B), mph(A) /mph(K)), tetracyclines ( tet(A), tet(B), tet(D), tet(G)), ansamycins ( arr), phenicols ( catA1/cat4, floR, cmlA, cmr), fluoroquinolones ( qnrS), quaternary amines ( qacEΔ 1), streptothricin ( sat2), sulfonamides ( sul1, sul2, sul3), and diaminopyrimidines ( dfrA1, dfrA5, dfrA7, dfrA8, dfrA12, dfrA13/21/22/23 family, dfrA14, dfrA15, dfrA16, dfrA17). This is the first profile of genes conferring resistance to multiple categories of antimicrobial agents in western and central Kenya. The large number and wide variety of resistance genes detected suggest the presence of significant selective pressure. The presence of five or more resistance determinants in almost two-thirds of the isolates points to the need for more effective, targeted public health policies and infection control/prevention measures.

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          Most cited references65

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          Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.

          Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided. © 2011 European Society of Clinical Microbiology and Infectious Diseases. No claim to original US government works.
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            Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors

            Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella spp., especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-β-lactamase (ESBL) producers. The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures.
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              Human intestinal bacteria as reservoirs for antibiotic resistance genes.

              Human intestinal bacteria have many roles in human health, most of which are beneficial or neutral for the host. In this review, we explore a more sinister side of intestinal bacteria; their role as traffickers in antibiotic resistance genes. Evidence is accumulating to support the hypothesis that intestinal bacteria not only exchange resistance genes among themselves but might also interact with bacteria that are passing through the colon, causing these bacteria to acquire and transmit antibiotic resistance genes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 June 2017
                2017
                : 12
                : 6
                : e0178880
                Affiliations
                [1 ]Center for Bio/Molecular Science & Engineering, Naval Research Laboratory, Washington, DC United States of America
                [2 ]US Army Medical Research Directorate-Kenya, Walter Reed Army Institute of Research, Kericho, Kenya
                [3 ]KEMRI/US Army Medical Research Directorate-Kenya, Walter Reed Army Institute of Research, Kericho, Kenya
                [4 ]Department of Global Health, University of Washington, Seattle, WA, United States of America
                [5 ]Departments of Pediatrics, Medicine, and Epidemiology, University of Washington, Seattle, WA, United States of America
                Ross University School of Veterinary Medicine, SAINT KITTS AND NEVIS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: CRT TAL CH GJV.

                • Data curation: CRT TAL DPE EAO JLW PBP CH GJV.

                • Formal analysis: CRT TAL PBP CH.

                • Funding acquisition: DPE JLW PBP GJV.

                • Investigation: CRT TAL DPE EAO NCK JNN RKK ANO CH.

                • Methodology: CRT TAL DPE CH GJV.

                • Project administration: CRT TAL DPE EAO JLW PBP CH GJV.

                • Resources: CRT TAL DPE EAO NCK JNN RKK ANO JLW PBP CH GJV.

                • Supervision: CRT DPE JLW PBP CH GJV.

                • Validation: CRT TAL DPE CH.

                • Visualization: CRT.

                • Writing – original draft: CRT TAL PBP CH GJV.

                • Writing – review & editing: CRT TAL DPE EAO NCK JNN RKK ANO JLW PBP CH GJV.

                Author information
                http://orcid.org/0000-0002-0125-9239
                Article
                PONE-D-17-08242
                10.1371/journal.pone.0178880
                5456380
                28575064
                11ee75a6-78cb-4bce-8ac0-d2fa99633937

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 1 March 2017
                : 19 May 2017
                Page count
                Figures: 0, Tables: 4, Pages: 19
                Funding
                This work was supported by the Office of Naval Research/NRL through internal Core funds [WU # 69-4888-05], the Armed Forces Health Surveillance Branch-Global Emerging Infections Surveillance and Response Systems (AFHSB-GEIS), and the National Institutes of Health [grant number U19-A2090882]. JLW and PBP are supported by the Center for AIDS Research (CFAR) Enterics Study Team (grant #AI027757) and PBP is also supported by the University of Washington STD/AIDS Research Training Program (grant number T32-AI007140). The funding sources had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobial Resistance
                Medicine and Health Sciences
                Pharmacology
                Antimicrobial Resistance
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Klebsiella Infections
                Research and Analysis Methods
                Bioassays and Physiological Analysis
                Microarrays
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Tetracyclines
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Tetracyclines
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Biology and Life Sciences
                Organisms
                Bacteria
                Klebsiella
                Klebsiella Pneumoniae
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Klebsiella
                Klebsiella Pneumoniae
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Klebsiella
                Klebsiella Pneumoniae
                Biology and Life Sciences
                Genetics
                Mutation
                Point Mutation
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. Additional gene sequence information for blaCTX-M-2, mac(A) and mac(B) sequences is available in NCBI (Accession numbers: KX377894, and KX377891 through KX377893).

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