Grup 2br, 2f, 2c β-laktamazlar
Özet
Antibiyotiklere karşı direnç oranları tüm dünyada artmaktadır. β-laktam antibiyotikler bakteriyel enfeksiyonların tedavisinde en yaygın kullanılan ilaçlardır. Bu antibiyotiklere karşı en yaygın direnç mekanizması ise β-laktamaz enzimleridir. β-laktamazlar, β-laktam halkasını hidrolize etme özelliği olan geniş bir enzim ailesidir. Bu enzimler çok sayıdadır ve antibiyotik kullanımının ağır baskısına yanıt olarak sürekli mutasyona uğrayarak genişlemiş spektrumlu β- laktamazların gelişmesine yol açarlar. β-laktamazların sınıflandırılmasında en sık Ambler moleküler sınıflandırması ile Bush-Jacoby-Medeiros fonksiyonel sınıflandırması kullanılmaktadır. Bu makalede Bush-Jacoby-Medeiros sınıflamasına göre 2br, 2c ve 2f sınıfında yer alan β-laktamazlar derlenmiştir. 2br sınıfındaki enzimler, β-laktamaz inhibitörlerine dirençli olmaları nedeniyle inhibitör dirençli TEM β-laktamazlar (IRT) olarak adlandırılırlar. 2c sınıfı enzimler, karbenisilin veya tikarsilini benzilpenisilinlere göre daha hızlı inaktive ederler. 2f sınıfı enzimler, karbapenemaz aktivitesi gösterirler. Tüm dünyada yaygın görülen Klebsiella pneumoniae karbapenemaz enzimi (KPC) bu sınıftadır. İşlevsel ve moleküler sınıflandırmalara göre enzimlerin farkındalığı ve saptanması hastaların optimal tedavisi için önemli ve gereklidir.
Resistance rates to antimicrobial agents are increasing worldwide. ß-lactam antibiotics are the most widely used agents in the treatment of bacterial infections. The most common mechanism of resistance to these agents is β-lactamase enzymes. ß-lactamases are large family of enzymes capable of hydrolyzing the β- lactam ring. These enzymes are numerous and are constantly mutating in response to the heavy pressure of antibiotic use, leading to the development of extended-spectrum β--lactamases. The Ambler molecular classification and the Bush-Jacoby-Medeiros functional classification are most commonly used to classify β- lactamases. This article reviews the β-lactamases in classes 2br, 2c and 2f according to the Bush-Jacoby-Medeiros classification. Enzymes in class 2br are called inhibitor-resistant TEM β- lactamases (IRT) because they are resistant to β lactamase inhibitors. Class 2c enzymes inactivate carbenicillin or ticarcillin more rapidly than benzylpenicillins. Class 2f enzymes show carbapenemase activity. The Klebsiella pneumoniae carbapenemase (KPC) enzyme, which is widespread worldwide, belongs to this class. Awareness and detection of enzymes according to functional and molecular classifications is important and necessary for optimal treatment of patients.
Referanslar
Samaha-Kfoury JN, Araj GF. Recent developments in β-lactamases and extended spectrum β- lactamases. BMJ 2003;327:1209–13.
Canto´n R, Morosini MI, Martin O, Maza S, Gomez G. de la Pedrosa G. IRT and CMT β-lactamases and inhibitor resistance. Clin Microbiol Infect 2008; 14 (1): 53–62.
Noguchi T, Matsumura Y, Kanahashi T, et al. Role of TEM-1 β-Lactamase in the Predominance of Ampicillin-Sulbactam-Nonsusceptible Escherichia coli in Japan. Antimicrob Agents Chemother 2019; 63(2): e02366-18
Rı´os E, Lo´ pez MC, Rodrı´guez-Avial I, Pena I, Picazo JJ. Characterization of Inhibitor-Resistant TEM β-Lactamases and Mechanisms of Fluoroquinolone Resistance in Escherichia coli isolates. Microb Drug Resist 2015: 21 (5): 512-515.
Uğraklı S, Doğan M. Overview of Β-Lactamases and Current Techniques for Detecting β-Lactamase Mediated Resistance. Ann Clin Med Microbiol 2018; 3(1): 1016-1022.
Bush K, F. Fisher J. Epidemiological Expansion, Structural Studies, and Clinical Challenges of New β-Lactamases from Gram-Negative Bacteria. Ann. Rev. Microbiol. 2011; 65: 455–78.
Chaibi EB, Sirot D, Paul G, Labia R. Inhibitor-resistant TEM β--lactamases: phenotypic, genetic and biochemical characteristics. J Antimicrob Chemother 1999; 43(4): 447-58.
Sawa T, Kooguchi K, Moriyama K. Molecular diversity of extended-spectrum β-lactamases and carbapenemases, and antimicrobial resistance. J Intensive Care 2020; 8(13): 1-13.
Naas T, Dortet L, Lorga BI. Structural and Functional Aspects of Class A Carbapenemases. Curr Drug Targets 2016;17(9):1006-28.
Bush K, Jacoby GA. Updated functional classification of β--lactamases. Antimicrob Agents Chemother. 2010; 54(3): 969-76.
Bush K, Bradford PA. Epidemiology of β-Lactamase-Producing Pathogens. Clin Microbiol Rev. 2020;33(2):e00047-19.
Bush K. Past and Present Perspectives on β-Lactamases. Antimicrob Agents Chemother 2018; 62(10): e01076-18.
Al-Bayssari C, Dabboussi F, Hamze F, Rolain JM. Detection of expanded spectrum b-lactamases in Gram-negative bacteria in the 21st century. Expert Rev Anti Infect Ther 2015;13(9):1139-58.
Tamma PD, Simner PJ. Phenotypic detection of carbapenemase producing organisms from clinical isolates. J Clin Microbiol 2018; 56:e01140-18.
Martínez-Martínez L, González-López JJ. Carbapenemases in Enterobacteriaceae: types and molecular epidemiology. Enferm Infect Microbiol Clin. 2014;32 (4): 4-9.
Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect. 2002; 8(6): 321-31.
Bush K. The ABCD’s of b-lactamase nomenclature J Infect Chemother 2013; 19: 549–559.
Walther-Rasmussen J, Høiby N. Class A carbapenemases. J Antimicrob Chemother. 2007; 60(3): 470-82.
Referanslar
Samaha-Kfoury JN, Araj GF. Recent developments in β-lactamases and extended spectrum β- lactamases. BMJ 2003;327:1209–13.
Canto´n R, Morosini MI, Martin O, Maza S, Gomez G. de la Pedrosa G. IRT and CMT β-lactamases and inhibitor resistance. Clin Microbiol Infect 2008; 14 (1): 53–62.
Noguchi T, Matsumura Y, Kanahashi T, et al. Role of TEM-1 β-Lactamase in the Predominance of Ampicillin-Sulbactam-Nonsusceptible Escherichia coli in Japan. Antimicrob Agents Chemother 2019; 63(2): e02366-18
Rı´os E, Lo´ pez MC, Rodrı´guez-Avial I, Pena I, Picazo JJ. Characterization of Inhibitor-Resistant TEM β-Lactamases and Mechanisms of Fluoroquinolone Resistance in Escherichia coli isolates. Microb Drug Resist 2015: 21 (5): 512-515.
Uğraklı S, Doğan M. Overview of Β-Lactamases and Current Techniques for Detecting β-Lactamase Mediated Resistance. Ann Clin Med Microbiol 2018; 3(1): 1016-1022.
Bush K, F. Fisher J. Epidemiological Expansion, Structural Studies, and Clinical Challenges of New β-Lactamases from Gram-Negative Bacteria. Ann. Rev. Microbiol. 2011; 65: 455–78.
Chaibi EB, Sirot D, Paul G, Labia R. Inhibitor-resistant TEM β--lactamases: phenotypic, genetic and biochemical characteristics. J Antimicrob Chemother 1999; 43(4): 447-58.
Sawa T, Kooguchi K, Moriyama K. Molecular diversity of extended-spectrum β-lactamases and carbapenemases, and antimicrobial resistance. J Intensive Care 2020; 8(13): 1-13.
Naas T, Dortet L, Lorga BI. Structural and Functional Aspects of Class A Carbapenemases. Curr Drug Targets 2016;17(9):1006-28.
Bush K, Jacoby GA. Updated functional classification of β--lactamases. Antimicrob Agents Chemother. 2010; 54(3): 969-76.
Bush K, Bradford PA. Epidemiology of β-Lactamase-Producing Pathogens. Clin Microbiol Rev. 2020;33(2):e00047-19.
Bush K. Past and Present Perspectives on β-Lactamases. Antimicrob Agents Chemother 2018; 62(10): e01076-18.
Al-Bayssari C, Dabboussi F, Hamze F, Rolain JM. Detection of expanded spectrum b-lactamases in Gram-negative bacteria in the 21st century. Expert Rev Anti Infect Ther 2015;13(9):1139-58.
Tamma PD, Simner PJ. Phenotypic detection of carbapenemase producing organisms from clinical isolates. J Clin Microbiol 2018; 56:e01140-18.
Martínez-Martínez L, González-López JJ. Carbapenemases in Enterobacteriaceae: types and molecular epidemiology. Enferm Infect Microbiol Clin. 2014;32 (4): 4-9.
Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect. 2002; 8(6): 321-31.
Bush K. The ABCD’s of b-lactamase nomenclature J Infect Chemother 2013; 19: 549–559.
Walther-Rasmussen J, Høiby N. Class A carbapenemases. J Antimicrob Chemother. 2007; 60(3): 470-82.
