Resistance to -Lactam Antibiotics: Structure and Mechanism Based Design of -Lactamase Inhibitors

Authors: Sandanayaka V.P.; Prashad A.S.

Source: Current Medicinal Chemistry, Volume 9, Number 12, June 2002 , pp. 1145-1165(21)

Publisher: Bentham Science Publishers

Abstract:

Resistance to antibiotics is currently a major health concern in treating infectious diseases. The most common mechanism of resistance to -lactam antibiotics is the production of -lactamases, which destroy -lactam antibiotics before they reach the bacterial target. Combination therapy, which involves treatment with a -lactam antibiotic and a -lactamase inhibitor, has been successfully used to control resistance during last two decades. Due to the lack of effectiveness of the currently available -lactamase inhibitors against class C enzymes and new variants of -lactamases, there is a need to develop an inhibitor with broad-spectrum activity. Since the discovery of clavulanic acid, there has been an enormous research effort in this area to identify better antibiotic / inhibitor combinations and to understand the molecular bases for interactions between -lactam antibiotics, -lactamases, and -lactamase inhibitors. This review describes some of the structure- and mechanism-based approaches to design of new -lactamase inhibitors and the study of probable mechanisms of inhibition using X-ray, electrospray ionization mass spectrometry, and molecular modeling techniques.

Keywords: beta-lactam antibioties; beta-lactamase; c enzymes; clavulanic acid

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/0929867023370031

Publication date: 2002-06-01

• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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