The multiple benefits of second-generation ?-lactamase inhibitors in treatment of multidrug-resistant bacteria - 02/09/21
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Highlights |
• | The World Health Organisation has designated antibiotic resistance as one of the most challenging public health threats of the 21st century. The production of β-lactamase enzymes by Gram-negative bacteria is the main mechanism of resistance to β-lactam (BL). This review is focused on the benefit of second-generation β-lactamase inhibitors (BLI), which function via different mechanisms and were developed by novel scaffolds from which diazabicyclooctane (DBOs) and boronic acids emerged. While several BL–BLI combinations are now being used in clinical practice; most of them are limited to clinical trials or pre-clinical studies. |
Abstract |
The World Health Organisation (WHO) has designated antibiotic resistance as one of the most challenging public health threats of the 21st century. Production of β-lactamase enzymes by Gram-negative bacteria is the main mechanism of resistance to β-lactam (BL), the most widely used antibiotic in clinics. In an attempt to neutralise the hydrolytic activity of these enzymes, β-lactamase inhibitors (BLIs) have been developed. First-generation BLIs include clavulanic acid, sulbactam and tazobactam. However, none of them cover all β-lactamase classes, and an increasingly wide panel of inhibitor-resistant bacterial strains has developed. Second-generation BLIs function via different mechanisms and were developed by novel scaffolds from which diazabicyclooctane (DBOs) and boronic acids have emerged. In this paper, we provide descriptions of promisor second-generation β-lactamase inhibitors, such as avibactam, vaborbactam and boronic acids, as well as several BL–BLI combinations that have been designed. While some combinations are now being used in clinical practice, most are presently limited to clinical trials or pre-clinical studies. In this paper, we emphasise the continuous need to develop novel and different BLIs to keep up with the multidrug-resistant bacteria that arise. At this time, however, second-generation BLIs constitute a promising and effective approach.
El texto completo de este artículo está disponible en PDF.Keywords : β-lactams, β-lactamase, β-lactamase inhibitors, Diazabicyclooctane, Boronic acids
Esquema
Vol 51 - N° 6
P. 510-517 - septembre 2021 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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