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      Acinetobacter baumannii: Epidemiological and Beta-Lactamase Data From Two Tertiary Academic Hospitals in Tshwane, South Africa

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          Abstract

          Acinetobacter baumannii is an opportunistic pathogen that is increasingly responsible for hospital-acquired infections. The increasing prevalence of carbapenem resistant A. baumannii has left clinicians with limited treatment options. Last line antimicrobials (i.e., polymyxins and glycylcyclines) are often used as treatment options. The aim of this study was to determine the prevalence of selected β-lactamase genes from A. baumannii isolates obtained from patients with hospital-acquired infections and to determine the genetic relationship and epidemiological profiles among clinical A. baumannii isolates collected from two tertiary academic hospitals in the Tshwane region, South Africa (SA). Multiplex-PCR (M-PCR) assays were performed to detect selected resistance genes. The collected isolates’ genetic relatedness was determined by using pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The acquired oxacillinase (OXA) genes, notably bla OXA-23-like were prevalent in the A. baumannii isolates. The M-PCR assays showed that the isolates collected from hospital A contained the OXA-23-like (96%; n = 69/72) genes and the isolates collected from hospital B contained the OXA-23-like (91%; n = 63/69) and OXA-58-like (4%; n = 3/69) genes. Colistin resistance was found in 1% of the isolates ( n = 2/141) and tigecycline intermediate resistance was found in 6% of the isolates ( n = 8/141). The A. baumannii isolates were genetically diverse. Molecular epidemiological data showed that specific sequence types (STs) (ST106, ST229, ST258 and ST208) were established in both hospitals, while ST848 was established in hospital A and ST502, ST339 and the novel ST1552 were established in hospital B. ST848 (established in hospital A) was predominately detected in ICU wards whereas ST208, ST339 and the novel ST1552 (established in hospital B) were detected in ICUs and the general wards. The origin of the A. baumannii isolates in the hospitals may be due to the dissemination and adaptation of a diverse group of successful clones. Poor infection control and prevention strategies and possibly the overuse of antimicrobials contributed to the establishment of these A. baumannii clones in the studied hospitals.

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          Most cited references52

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          Standardization of pulsed-field gel electrophoresis protocols for the subtyping of Escherichia coli O157:H7, Salmonella, and Shigella for PulseNet.

          Standardized rapid pulsed-field gel electrophoresis (PFGE) protocols for the subtyping of Escherichia coli O157:H7, Salmonella serotypes, and Shigella species are described. These protocols are used by laboratories in PulseNet, a network of state and local health departments, and other public health laboratories that perform real-time PFGE subtyping of these bacterial foodborne pathogens for surveillance and outbreak investigations. Development and standardization of these protocols consisted of a thorough optimization of reagents and reaction conditions to ensure that the protocols yielded consistent results and high-quality PFGE pattern data in all the PulseNet participating laboratories. These rapid PFGE protocols are based on the original 3-4-day standardized procedure developed at Centers for Disease Control and Prevention that was validated in 1996 and 1997 by eight independent laboratories. By using these rapid standardized PFGE protocols, PulseNet laboratories are able to subtype foodborne pathogens in approximately 24 h, allowing for the early detection of foodborne disease case clusters and often aiding in the identification of the source responsible for the infections.
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            OXA β-lactamases.

            The OXA β-lactamases were among the earliest β-lactamases detected; however, these molecular class D β-lactamases were originally relatively rare and always plasmid mediated. They had a substrate profile limited to the penicillins, but some became able to confer resistance to cephalosporins. From the 1980s onwards, isolates of Acinetobacter baumannii that were resistant to the carbapenems emerged, manifested by plasmid-encoded β-lactamases (OXA-23, OXA-40, and OXA-58) categorized as OXA enzymes because of their sequence similarity to earlier OXA β-lactamases. It was soon found that every A. baumannii strain possessed a chromosomally encoded OXA β-lactamase (OXA-51-like), some of which could confer resistance to carbapenems when the genetic environment around the gene promoted its expression. Similarly, Acinetobacter species closely related to A. baumannii also possessed their own chromosomally encoded OXA β-lactamases; some could be transferred to A. baumannii, and they formed the basis of transferable carbapenem resistance in this species. In some cases, the carbapenem-resistant OXA β-lactamases (OXA-48) have migrated into the Enterobacteriaceae and are becoming a significant cause of carbapenem resistance. The emergence of OXA enzymes that can confer resistance to carbapenems, particularly in A. baumannii, has transformed these β-lactamases from a minor hindrance into a major problem set to demote the clinical efficacy of the carbapenems.
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              Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options.

              Multidrug-resistant Acinetobacter baumannii is recognized to be among the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. Increasing antimicrobial resistance among Acinetobacter isolates has been documented, although definitions of multidrug resistance vary in the literature. A. baumannii survives for prolonged periods under a wide range of environmental conditions. The organism causes outbreaks of infection and health care-associated infections, including bacteremia, pneumonia, meningitis, urinary tract infection, and wound infection. Antimicrobial resistance greatly limits the therapeutic options for patients who are infected with this organism, especially if isolates are resistant to the carbapenem class of antimicrobial agents. Because therapeutic options are limited for multidrug-resistant Acinetobacter infection, the development or discovery of new therapies, well-controlled clinical trials of existing antimicrobial regimens and combinations, and greater emphasis on the prevention of health care-associated transmission of multidrug-resistant Acinetobacter infection are essential.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                12 June 2018
                2018
                : 9
                : 1280
                Affiliations
                [1] 1Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria , Pretoria, South Africa
                [2] 2Department of Medical Microbiology, Tshwane Academic Division, National Health Laboratory Service , Pretoria, South Africa
                [3] 3Departments of Microbiology, Immunology, Infectious Diseases and Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada
                [4] 4Division of Microbiology, Calgary Laboratory Services , Calgary, AB, Canada
                [5] 5Research Office, Faculty of Health Sciences, University of Pretoria , Pretoria, South Africa
                Author notes

                Edited by: Jorge Blanco, Universidade de Santiago de Compostela, Spain

                Reviewed by: Vanesa García, Universidade de Santiago de Compostela, Spain; Javier Fernández, Central University Hospital of Asturias, Spain

                *Correspondence: Marleen M. Kock, marleen.kock@ 123456up.ac.za

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2018.01280
                6005857
                29946315
                db19928b-ae83-431a-b999-2cd7475dea30
                Copyright © 2018 Lowe, Ehlers, Ismail, Peirano, Becker, Pitout and Kock.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 February 2018
                : 25 May 2018
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 63, Pages: 9, Words: 0
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                acinetobacter baumannii,mdr,south africa,pfge,mlst,blaoxa-23-like
                Microbiology & Virology
                acinetobacter baumannii, mdr, south africa, pfge, mlst, blaoxa-23-like

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