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      Acinetobacter baumannii Sequence Types Harboring Genes Encoding Aminoglycoside Modifying Enzymes and 16SrRNA Methylase; a Multicenter Study from Pakistan

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          Abstract

          Introduction

          The aminoglycosides are widely used for the therapeutic management of infections caused by gram-negative bacteria, including the Acinetobacter baumannii strains. However, the resistance to the members of the aminoglycoside family, such as amikacin, gentamicin, and tobramycin, is increasingly being common among the clinical isolates.

          Purpose

          This study aimed to investigate the presence of 16SrRNA methylases and aminoglycoside modifying enzymes (AMEs) genes among aminoglycoside resistant A. baumannii isolates and to study the genetic diversity of the clinical population of A. baumannii in local hospitals.

          Material and Methods

          The 143 A. baumannii clinical strains were analyzed for antimicrobial susceptibility, genetic screening for enzymes conferring aminoglycosides resistance followed by the multilocus sequence typing.

          Results

          The 133/143 (93%) isolates were non-susceptible to at least one of the tested aminoglycosides, including amikacin, gentamicin, and tobramycin. The MIC distribution has shown that 87.486.7% strains were resistant to amikacin and gentamicin, respectively. The aphA6, aadB, aacC1, and aphA1 were found in 74.1%, 59.4%, 16.1%, and 11.2% isolates, respectively, whereas the armA was found in 28% of the strains having a higher MIC value (MIC; ≥256µg/mL). The MLST data have shown that the ST589 and ST2 were the most common STs and corresponded to 51 (35.7%) and 38 (26.6%) isolates, respectively, and few of the isolates corresponding to these STs were found to harbor the armA gene with a variable genotypic profile for AMEs.

          Discussion

          The study has reported the incidence of various enzymes conferring aminoglycoside resistance among the A. baumannii clones for the first time from Pakistan. The findings suggest the possibility of transmission of aminoglycoside resistance determinants through the lateral gene transfer as well as clonal dissemination.

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          Most cited references27

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          Antibiotics and Bacterial Resistance in the 21st Century

          Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed.
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            Combination therapy for treatment of infections with gram-negative bacteria.

            Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria.
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              Versatility of aminoglycosides and prospects for their future.

              Aminoglycoside antibiotics have had a major impact on our ability to treat bacterial infections for the past half century. Whereas the interest in these versatile antibiotics continues to be high, their clinical utility has been compromised by widespread instances of resistance. The multitude of mechanisms of resistance is disconcerting but also illuminates how nature can manifest resistance when bacteria are confronted by antibiotics. This article reviews the most recent knowledge about the mechanisms of aminoglycoside action and the mechanisms of resistance to these antibiotics.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                idr
                idr
                Infection and Drug Resistance
                Dove
                1178-6973
                18 August 2020
                2020
                : 13
                : 2855-2862
                Affiliations
                [1 ]Institute of Antibiotics, Huashan Hospital, Fudan University , Shanghai 200040, People’s Republic of China
                [2 ]Department of Microbiology, Government College University , Faisalabad, Pakistan
                [3 ]Department of Bioinformatics & Biotechnology, Government College University , Faisalabad, Pakistan
                [4 ]School of Biological Sciences, University of the Punjab , Lahore, Pakistan
                [5 ]Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University , Buraydah, Saudi Arabia
                [6 ]Allama Iqbal Medical College, Jinnah Hospital Lahore , Lahore, Pakistan
                Author notes
                Correspondence: Mohsin KhurshidDepartment of Microbiology, Government College University , Faisalabad, PakistanTel +923334301513 Email mohsinkhurshid@gcuf.edu.pk
                Author information
                http://orcid.org/0000-0002-3196-2857
                http://orcid.org/0000-0002-5495-805X
                http://orcid.org/0000-0002-5495-5561
                http://orcid.org/0000-0003-4883-3506
                http://orcid.org/0000-0002-1491-6402
                http://orcid.org/0000-0002-5404-1970
                http://orcid.org/0000-0001-7682-5859
                Article
                260643
                10.2147/IDR.S260643
                7443399
                32884309
                d074fcc8-6d01-48ad-8ce9-592a78a8fb93
                © 2020 Khurshid et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 30 April 2020
                : 29 July 2020
                Page count
                Figures: 0, Tables: 3, References: 32, Pages: 8
                Funding
                Funded by: the National Natural Science Foundation of China;
                Funded by: Higher Education Commission (HEC) of Pakistan;
                This work was supported by grants from the National Natural Science Foundation of China (grant # 81773785, 81603163 and 81473250) and Higher Education Commission (HEC) of Pakistan (grant # 5679/Punjab/NRPU/R&D/HEC/2016).
                Categories
                Original Research

                Infectious disease & Microbiology
                aminoglycosides,arma,mlst,gentamicin,a. baumannii
                Infectious disease & Microbiology
                aminoglycosides, arma, mlst, gentamicin, a. baumannii

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