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      Preliminary survey of extended-spectrum β-lactamases (ESBLs) in nosocomial uropathogen Klebsiella pneumoniae in north-central Iran

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          Abstract

          Infections caused by extended-spectrum β-lactamases (ESBLs) producing bacteria, including Klebsiella pneumoniae have increasingly subjected to therapeutic limitations and patients with these infections are at high risk for treatment failure, long hospital stays, high health care costs, and high mortality. The aim of this study was to screen the prevalence of the bla TEM, bla CTX-M and bla SHV ESBL genes in K. pneumoniae strains isolated from nosocomial urinary tract infections (UTIs). During the March 2016 to December 2017, one hundred isolates of K. pneumoniae were collected from urine specimens of patients suffering from nosocomial UTI referred to Khatam Al-Anbia hospital in Shahrud, north-central Iran. All isolates were identified by standard bacteriological tests. The pattern of antibiotic susceptibility was determined according to the CLSI guidelines. The presence of the ESBLs was investigated using the double-disc synergy test (DDST). Polymerase chain reaction technique was used to detect the bla TEM, bla CTX-M and bla SHV genes in DDST positive isolates. Most isolates showed remarkable resistance to tested antibiotics with highest rate against nitrofurantoin (75%) and trimethoprim/sulfamethoxazole (65%). The imipenem was the most effective antibiotic against K. pneumoniae isolates. ESBL phenotype was detected in 50 (50%) of isolates. The prevalence of bla TEM, bla CTX-M and bla SHV genes among 50 ESBLs-positive isolates was 25 (50%), 15 (30%) and 35 (70%) respectively. The bla TEM and bla SHV genes were seen in 25 isolates (50%) simultaneously. The findings of this study indicated the 50% frequency rate of ESBL-producing K. pneumoniae in our geographic region. Since the treatment of infections caused by this bacterium is associated with many limitations, this high prevalence is a warning sign to adopt new control policies to prevent further spread of this microorganism.

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          Extended-Spectrum β-Lactamases: a Clinical Update

          Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli . In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
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            Extended-spectrum β-lactamases in Gram Negative Bacteria

            Extended-spectrum β-lactamases (ESBLs) are a group of plasmid-mediated, diverse, complex and rapidly evolving enzymes that are posing a major therapeutic challenge today in the treatment of hospitalized and community-based patients. Infections due to ESBL producers range from uncomplicated urinary tract infections to life-threatening sepsis. Derived from the older TEM is derived from Temoniera, a patient from whom the strain was first isolated in Greece. β-lactamases, these enzymes share the ability to hydrolyze third-generation cephalosporins and aztreonam and yet are inhibited by clavulanic acid. In addition, ESBL-producing organisms exhibit co-resistance to many other classes of antibiotics, resulting in limitation of therapeutic option. Because of inoculum effect and substrate specificity, their detection is also a major challenge. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in Klebsiella pneumoniae, K. oxytoca, Escherichia coli and Proteus mirabilis. In common to all ESBL-detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic-resistance mechanisms in the face of the introduction of new antimicrobial agents. Thus there is need for efficient infection-control practices for containment of outbreaks; and intervention strategies, e.g., antibiotic rotation to reduce further selection and spread of these increasingly resistant pathogens.
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              The Growing Genetic and Functional Diversity of Extended Spectrum Beta-Lactamases

              The β-lactams—a large class of diverse compounds—due to their excellent safety profile and broad antimicrobial spectrum are considered to be the most widely used therapeutic class of antibacterials prescribed in human and veterinary clinical practices. This, unfortunately, has also given rise to a continuous increased resistance globally in health care settings as well as in the community due to their permanent selective force driving diversification of the resistance mechanism. Resistance against β-lactams is increasing rapidly as novel β-lactamases, enzymes that degrade β-lactams, are being discovered each day such as recent emergence of extended spectrum β-lactamases (ESBL) that have the ability to inactivate most of the cephalosporins. The complexity and diversity of ESBL are increasing so rapidly that more than 170 variants have thus far been described for only a single genotype, the bla CTX-M -encoding ESBL. This review is to organize all the current updated literature describing genomic features, organization, and mechanism of resistance and mode of dissemination of all known ESBLs.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                17 September 2019
                September 2019
                17 September 2019
                : 5
                : 9
                : e02349
                Affiliations
                [a ]Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
                [b ]Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
                [c ]Community Health Department, College of Health and Medical Techniques, Al-Furat Al-Awsat Technical University, Kufa, Iraq
                [d ]Department of Microbiology, Qom Branch, Islamic Azad University, Qom, Iran
                [e ]Department of Microbiology, Dentistry College of Basic Science, Basrah University, Basrah, Iraq
                [f ]Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                [g ]Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                [h ]Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                [i ]Department of Laboratory Sciences, Taleghani Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                [j ]Department of Microbiology, Emam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                [k ]Department of Laboratory Sciences, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                Author notes
                []Corresponding author. mortezasaki1981@ 123456gmail.com
                Article
                S2405-8440(19)36009-8 e02349
                10.1016/j.heliyon.2019.e02349
                6819946
                31687535
                2b9dfdd0-d92e-4e9e-8525-c29b43de9053
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 20 May 2019
                : 3 July 2019
                : 16 August 2019
                Categories
                Article

                microbiology,extended spectrum beta-lactamases,esbl,blatem,blactx-m,klebsiella pneumoniae,multidrug-resistant,iran

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