The inhibition of class C <i>β</i>-lactamases by boronic acids

Beesley, T; Gascoyne, N; Knott-Hunziker, V; Petursson, S.; Waley, S. G.; Jaurin, Bengtåke; Grundström, Thomas

doi:10.1042/bj2090229

Cited by 150 publications

(114 citation statements)

References 23 publications

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“…Boronic acids (BA) were reported in the early 1980s to be reversible inhibitors of class C enzymes (1). Unexpectedly, we discovered unusual inhibition of organisms possessing KPC by 3-aminophenylboronic acid (APB), which may be attributed solely to the presence of this carbapenemase (25).…”

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confidence: 84%

Sensitive Screening Tests for Suspected Class A Carbapenemase Production in Species of Enterobacteriaceae

et al. 2009

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The detection of class A serine-carbapenemases among species of Enterobacteriaceae remains a challenging issue. Methods of identification for routine use in clinical microbiology laboratories have not been standardized to date. We developed a novel screening methodology suitable for countries with high basal levels of carbapenem resistance due to non-carbapenemase-mediated mechanisms and standardized several simple confirmatory methods that allow the recognition of bacteria producing class A carbapenemases, including KPC, Sme, IMI, NMC-A, and GES, by using boronic acid (BA) derivatives. A total of 28 genetically unrelated Enterobacteriaceae strains producing several class A carbapenemases were tested. Thirty-eight genetically unrelated negative controls were included. The isolates were tested against imipenem (IPM), meropenem (MEM), and ertapenem (ETP) by MIC and disk diffusion assays in order to select appropriate tools to screen for suspected carbapenemase production. It was possible to differentiate class A carbapenemase-producing bacteria from non-carbapenemase-producing bacteria by using solely the routine IPM susceptibility tests. The modified Hodge test was evaluated and found to be highly sensitive, although false-positive results were documented. Novel BA-based methods (a double-disk synergy test and combined-disk and MIC tests) using IPM, MEM, and ETP, in combination with 3-aminophenylboronic acid as an inhibitor, were designed as confirmatory tools. On the basis of the performance of these methods, a sensitive flow chart for suspicion and confirmation of class A carbapenemase production in species of Enterobacteriaceae was designed. By using this methodology, isolates producing KPC, GES, Sme, IMI, and NMC-A carbapenemases were successfully distinguished from those producing other classes of ␤-lactamases (extended-spectrum ␤-lactamases, AmpCs, and metallo-␤-lactamases, etc). These methods will rapidly provide useful information needed for targeting antimicrobial therapy and appropriate infection control.

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Sensitive Screening Tests for Suspected Class A Carbapenemase Production in Species of Enterobacteriaceae

et al. 2009

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“…Thus, practical, highly sensitive, and highly specific methods for the detection of KPC-possessing isolates are needed for regions where other carbapenem-resistant determinants are also prevalent. Boronic acid compounds are known class C enzyme inhibitors, which are not based on a ␤-lactam structure (2). Disk tests based on their inhibitory activities were originally reported for the detection of plasmid-mediated AmpC enzymes among enterobacterial pathogens (7,9).…”

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confidence: 99%

Evaluation of Boronic Acid Disk Tests for Differentiating KPC-Possessing Klebsiella pneumoniae Isolates in the Clinical Laboratory

et al. 2009

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The worldwide increase in the occurrence and dissemination of KPC ␤-lactamases among gram-negative pathogens makes critical the early detection of these enzymes. Boronic acid disk tests using different antibiotic substrates were evaluated for detection of KPC-possessing Klebsiella pneumoniae isolates. A total of 57 genotypically confirmed KPC-possessing K. pneumoniae isolates with varying carbapenem MICs were examined. To measure the specificity of the tests, 106 non-KPC-possessing isolates (89 K. pneumoniae and 17 Escherichia coli isolates) were randomly selected among those exhibiting reduced susceptibility to cefoxitin, expanded-spectrum cephalosporins, or carbapenems. As many as 56, 53, and 40 of the non-KPC-possessing isolates harbored extended-spectrum ␤-lactamases, metallo-␤-lactamases, and plasmidmediated AmpC ␤-lactamases, respectively. By use of CLSI methodology and disks containing imipenem, meropenem, or cefepime, either alone or in combination with 400 g of boronic acid, all 57 KPC producers gave positive results (sensitivity, 100%) whereas all 106 non-KPC producers were negative (specificity, 100%). The meropenem duplicate disk with or without boronic acid demonstrated the largest differences in inhibition zone diameters between KPC producers and non-KPC producers. By use of disks containing ertapenem, all isolates were correctly differentiated except for five AmpC producers that gave falsepositive results (sensitivity, 100%; specificity, 95.3%). These practical and simple boronic acid disk tests promise to be very helpful for the accurate differentiation of KPC-possessing K. pneumoniae isolates, even in regions where different broad-spectrum ␤-lactamases are widespread.

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“…El hallazgo de un paciente con infecciones producidas por EPC reduce las opciones terapéuticas y promueve el inicio de combinaciones de antibióticos, algunos de alta toxicidad y la aplicación de medidas de prevención y contención, por lo cual su tipo AmpC con impermeabilidad continúan siendo un inconveniente 16,17,5 . Por su parte el MIC*, en nuestro estudio no se demostró este tipo de resultados, presentando una sensibilidad y especificidad muy cercana al 100% para detectar carbapenemasas blaKPC en enterobacterias.…”

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Inactivación del carbapenémico, un método alternativo para detectar carbapenemasa tipo KPC en Enterobacteriaceae

Reyes

Villacís

Chicaiza-Alomoto

et al. 2017

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Cómo citar este artículo: J.A. Reyes-Chacón, et al. Inactivación del carbapené-mico, un método alternativo para detectar carbapenemasa tipo KPC en Enterobacteriaceae. Infectio 2017; 21(4): 251-254 ResumenObjetivo: Evaluar al método de inactivación del carbapenémico (MIC*) frente a técnicas como el Test de Hodge modificado (THM), ácido 3-aminofenilborónico (APB) y la reacción en cadena de la polimerasa en enterobacterias productoras de carbapenemasas (EPC) tipo KPC. Materiales y métodos: Se seleccionaron 88 aislados clínicos de K. pneumoniae, K. oxytoca, E.coli, S. marcescens, C. freundii sensibles y 91 resistentes a los carbapenémicos. El APB y el método MIC* se realizaron siguiendo las publicaciones originales. El THM se realizó de acuerdo al CLSI 100S Edición 26-2016. El gen blaKPC se identificó por multiplex PCR. Resultados: El MIC* en EPC tipo KPC presentó una sensibilidad/especificidad cercana al 100% y kappa de 1 comparado con la PCR; se observó la ausencia de halo en todas los aislados EPC tipo KPC a diferencia de los aislados sensibles a los cabapenémicos que presentaron halo > 19mm. Se observó el 3 % de resultados falsos positivos y el 5 % de falsos negativos en THM y ABP respectivamente. Discusión y conclusiones: El MIC* y la PCR demuestran superioridad al THM y ABP para identificar carbapenemasas tipo KPC en EPC. Se recomienda su uso de forma rutinaria dentro del algoritmo para la contención de infecciones por este tipo de patógenos.Palabras clave: carbapenemasa, Enterobacteria, reacción en cadena de la polimerasa, inactivación. Carbapenem inactivation, an alternative method to detect carbapenemase type KPC in Enterobacteriacea AbstractObjective: To compare the carbapenem inactivation method (CIM *) with the Modified Hodge Test (MHT), the acid 3-aminophenylboronic test(APB) and the polymerase chain reaction (PCR) detection of the blaKPC gene for the identification of KPC carbapenemase producing Enterobacteriaceae (ECP). Materials and Methods:We selected 88 susceptible and 91 carbapenems resistant clinical isolates of Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Serratia marcescens and Citrobacter freundii. We performed APB and CIM* according to previously published methods and the MHT according to CLSI 100S Edition 26-2016. The blaKPC gene was identified by PCR multiplex. Results: The CIM* had a sensitivity and specificity close to 100% and a kappa score of 1 compared with gold standard PCR. The absence of zone diameter was observed in all isolated KPC producers, unlike in isolates susceptible to carbapenems, where a zone diameter >19mm was observed. Three percent of false positive and five percent of false negative was observed in THM and ABP respectively. Discussion and conclusions: The CIM* and the PCR were better than MHT and ABP at identifying carbapenemases in ECP. We recommend the routine use of the CIM* within the algorithm for ECP infection control.Keywords: carbapenemase, Enterobacteriacea, polymerase chain reaction, inactivation. IntroducciónLa emergencia de enterobacterias ...

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The inhibition of class C β-lactamases by boronic acids

Cited by 150 publications

References 23 publications

Sensitive Screening Tests for Suspected Class A Carbapenemase Production in Species of Enterobacteriaceae

Sensitive Screening Tests for Suspected Class A Carbapenemase Production in Species of Enterobacteriaceae

Evaluation of Boronic Acid Disk Tests for Differentiating KPC-Possessing Klebsiella pneumoniae Isolates in the Clinical Laboratory

Inactivación del carbapenémico, un método alternativo para detectar carbapenemasa tipo KPC en Enterobacteriaceae

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