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Lactamase Inhibitors (lactamase + inhibitor)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Molecular basis of antibiotic resistance and ,-lactamase inhibition by mechanism-based inactivators: perspectives and future directions

FEMS MICROBIOLOGY REVIEWS, Issue 3 2000
Christian Therrien
Abstract Antibacterial chemotherapy is particularly striking in the family of penicillins and cephalosporins. Over 40 structurally different ,-lactam molecules are available in 73 formulations and the majority of them are currently prescribed for medical use in hospitals. ,-Lactams are well tolerated by humans with few side effects. They interact very specifically with their bacterial target, the d -alanyl- d -alanine carboxypeptidase-transpeptidase usually referred to as dd -peptidase. The outstanding number of ,-lactamases produced by bacteria represent a serious threat to the clinical utility of ,-lactams. The discovery of ,-lactamase inhibitors was thought to solve, in part, the problem of resistance. Unfortunately, bacteria have evolved new mechanisms of resistance to overcome the inhibitory effects of ,-lactamase inactivators. Here, we summarize the diversified mechanistic features of class A ,-lactamases interactions with mechanism-based inhibitors using available microbiological, kinetic and structural data for the prototype TEM ,-lactamases. A brief historical overview of the strategies developed to counteract ,-lactamases will be presented followed by a short description of the chemical events which lead to the inactivation of TEM ,-lactamase by inhibitors from different classes. Finally, an update on the clinical prevalence of natural and inhibitor-resistant enzyme mutants, the total chemical synthesis to design and synthesize a new structure and produced a broad spectrum ,-lactamase inhibitor that mimics the ,-lactam ring, but does not contain it is discussed. [source]

Screening of some medicinal plants from cameroon for , -Lactamase inhibitory activity

PHYTOTHERAPY RESEARCH, Issue 3 2007
Joseph Gangoué-Piéboji
Abstract In efforts to find new bioactive , -lactamase inhibitors, this study investigated 16 Cameroonian plants belonging to 10 families which were evaluated for anti- , -lactamase activity. The investigation showed that extracts 2, 6, 3 and 5 of the 16 plants investigated presented interesting in vitro, -lactamase inhibition (over 90%), respectively, of the , -lactamases TEM-1, OXA-10, IMP-1 and P99. These extracts were from Mammea africana (all , -lactamases), Garcinia lucida, G. kola (OXA-10, IMP-1 and P99), Bridelia micrantha (OXA-10, P99), Ochna afzelii (OXA-10, P99), Prunus africana (IMP-1) and Adenia lobata (TEM-1). After elimina tion of tannins (according to the European Pharmacopoeia) the extracts from B. micrantha, G. lucida and M. africana were tested further for their anti- , -lactamase activity. The extracts from B. micrantha and G. lucida exhibited potent inhibitory activity, respectively, of , -lactamase OXA-10 (IC50 = 0.02 mg/mL) and P99 (IC50 = 0.01 mg/mL). The anti- , -lactamase activity of M. africana extract was weak. The isolation and the structural elucidation of the active constituents of G. lucida and B. micrantha will provide useful leads in the development of , -lactamase inhibitors. Copyright © 2007 John Wiley & Sons, Ltd. [source]

The emergence and implications of metallo-,-lactamases in Gram-negative bacteria

CLINICAL MICROBIOLOGY AND INFECTION, Issue 2005
T. R. Walsh
Abstract The increase in Gram-negative broad-spectrum antibiotic resistance is worrisome, particularly as there are few, if any, ,,pipeline'' antimicrobial agents possessing suitable activity against Pseudomonas spp. or Acinetobacter spp. The increase in resistance will be further enhanced by the acquisition of metallo-,-lactamase (MBL) genes that can potentially confer broad-spectrum ,-lactam resistance. These genes encode enzymes that can hydrolyse all classes of ,-lactams and the activity of which cannot be neutralised by ,-lactamase inhibitors. MBL genes are often associated with aminoglycoside resistant genes and thus bacteria that possess MBL genes are often co-resistant to aminoglycosides, further compromising therapeutic regimes. Both types of genes can be found as gene cassettes carried by integrons that in turn are embedded within transposons providing a highly ambulatory genetic element. The dissemination of MBL genes is typified by the spread of blaVIM-2, believed to originate from a Portuguese patient in 1995, and is now present in over 20 counties. The increase in international travel is likely to be a contributory factor for the ascendancy of mobile MBL genes as much as the mobility among individual bacteria. Fitness, acquisition and host dependency are key areas that need to be addressed to enhance our understanding of how antibiotic resistance spreads. There is also a pressing need for new, and hopefully novel, compounds active against pan-resistant Gram-negative bacteria , a growing problem that needs to be addressed by both government and industry. [source]