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Clinical Microbiology Reviews, April 2005, p. 306-325, Vol. 18, No. 2
0893-8512/05/$08.00+0     doi:10.1128/CMR.18.2.306-325.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Metallo-ß-Lactamases: the Quiet before the Storm?

Timothy R. Walsh,1* Mark A. Toleman,1 Laurent Poirel,2 and Patrice Nordmann2

Department of Pathology and Microbiology, University of Bristol, Bristol, United Kingdom,1 Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France2

The ascendancy of metallo-ß-lactamases within the clinical sector, while not ubiquitous, has nonetheless been dramatic; some reports indicate that nearly 30% of imipenem-resistant Pseudomonas aeruginosa strains possess a metallo-ß-lactamase. Acquisition of a metallo-ß-lactamase gene will invariably mediate broad-spectrum ß-lactam resistance in P. aeruginosa, but the level of in vitro resistance in Acinetobacter spp. and Enterobacteriaceae is less dependable. Their clinical significance is further embellished by their ability to hydrolyze all ß-lactams and by the fact that there is currently no clinical inhibitor, nor is there likely to be for the foreseeable future. The genes encoding metallo-ß-lactamases are often procured by class 1 (sometimes class 3) integrons, which, in turn, are embedded in transposons, resulting in a highly transmissible genetic apparatus. Moreover, other gene cassettes within the integrons often confer resistance to aminoglycosides, precluding their use as an alternative treatment. Thus far, the metallo-ß-lactamases encoded on transferable genes include IMP, VIM, SPM, and GIM and have been reported from 28 countries. Their rapid dissemination is worrisome and necessitates the implementation of not just surveillance studies but also metallo-ß-lactamase inhibitor studies securing the longevity of important anti-infectives.

* Corresponding author. Mailing address: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom. Phone: 44 117 9288819. Fax: 44 117 9287896. E-mail: t.r.walsh{at}bristol.ac.uk.

Clinical Microbiology Reviews, April 2005, p. 306-325, Vol. 18, No. 2
0893-8512/05/$08.00+0     doi:10.1128/CMR.18.2.306-325.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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