Extended-spectrum beta-lactamases: A clinical update

Paterson, David L. and Bonomo, Robert A. (2005) Extended-spectrum beta-lactamases: A clinical update. Clinical Microbiology Reviews, 18 4: 657-686. doi:10.1128/CMR.18.4.657-686.2005

Author Paterson, David L.
Bonomo, Robert A.
Title Extended-spectrum beta-lactamases: A clinical update
Formatted title
Extended-spectrum β-lactamases: A clinical update
Journal name Clinical Microbiology Reviews   Check publisher's open access policy
ISSN 0893-8512
Publication date 2005-10
Year available 2005
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1128/CMR.18.4.657-686.2005
Volume 18
Issue 4
Start page 657
End page 686
Total pages 30
Place of publication Washington, D.C., U.S.A.
Publisher American Society for Microbiology
Language eng
Subject 1101 Medical Biochemistry and Metabolomics
1108 Medical Microbiology
1115 Pharmacology and Pharmaceutical Sciences
Abstract Extended-spectrum ß-lactamases (ESBLs) are a rapidly evolving group of ß-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these ß-lactamases. This extends the spectrum of ß-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.
Keyword ß-lactamases
Clavulanic acid
Q-Index Code C1

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
UQ Centre for Clinical Research Publications
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Citation counts: TR Web of Science Citation Count  Cited 1210 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 25 Jan 2010, 12:14:16 EST by Macushla Boyle on behalf of Royal Brisbane Clinical School