Carbapenem-hydrolyzing beta-lactamases

Rasmussen, Beth A.; Bush, Karen

doi:10.1128/aac.41.2.223

Cited by 358 publications

(224 citation statements)

References 88 publications

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“…chromosomal or acquired AmpC) tends to compromise the use of these agents in metallo-b-lactamase-producing strains. Naturally occurring, generally chromosomal class B metallo-b-lactamases have been described in a number of environmental species, most of which are of limited clinical significance [23,24,208]. A number of clinical Burkholderia cepacia isolates producing an inducible metalloenzyme (PCM-I) that also shows preferential hydrolysis of carbapenems/imipenem have also been described [208].…”

Section: Class B Metallo-b B-lactamasesmentioning

confidence: 99%

Resistance to ?-lactam antibiotics

Poole

2004

CMLS, Cell. Mol. Life Sci.

290

218

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beta-lactams have a long history in the treatment of infectious diseases, though their use has been and continues to be confounded by the development of resistance in target organisms. beta-lactamases, particularly in Gram-negative pathogens, are a major determinant of this resistance, although alterations in the beta-lactam targets, the penicillin-binding proteins (PBPs), are also important, especially in Gram-positive pathogens. Mechanisms for the efflux and/or exclusion of these agents also contribute, though often in conjunction these other two. Approaches for overcoming these resistance mechanisms include the development of novel beta-lactamase-stable beta-lactams, beta-lactamase inhibitors to be employed with existing beta-lactams, beta-lactam compounds that bind strongly to low-affinity PBPs and agents that potentiate the activity of existing beta-lactams against low-affinity PBP-producing organisms.

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Section: Class B Metallo-b B-lactamasesmentioning

confidence: 99%

Resistance to ?-lactam antibiotics

Poole

2004

CMLS, Cell. Mol. Life Sci.

290

218

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“…They inactivate penicillins, cephalosporins, cephamycins, oxyiminocephalosporins, and aztreonam, and they are more active against imipenem than against meropenem [44]. The activity of the ␤-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) is variable.…”

Section: Carbapenemasesmentioning

confidence: 98%

“…Currently, there are 18 characterized carbapenemases. As a distinct group, these ␤-lactamases are preferentially active against carbapenems but also hydrolyze penicillins and cephalosporins [44].…”

Section: Carbapenemasesmentioning

confidence: 99%

“…Of the class A carbapenemases, three unique enzymes have been found: E. cloacae strains 1413B and NOR-1 encode IMI-1 and NmcA, respectively, and S. marcescens strains S6 and S8 encode SME-1. The serine ␤-lactamases are generally plasmid encoded in enterobacterial strains; the metalloenzymes may be either chromosomal encoded or plasmid encoded [44].…”

Section: Carbapenemasesmentioning

confidence: 99%

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The red menace: Emerging issues in antimicrobial resistance in gram-negative bacilli

Rice

1999

Curr Infect Dis Rep

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Gram-negative bacilli cause more than one third of all nosocomial infections in US hospitals. Despite a surfeit of new and highly potent antimicrobial agents, the problem of resistance in these pathogens continues to increase. Particularly important is the emergence of resistance to the fluoroquinolone and beta-lactam classes of antimicrobial agents. Recent work has confirmed that resistance to fluoroquinolone antibiotics is a complex process that involves mutations in the target enzymes (topoisomerase II and IV), decreased access to the target enzyme resulting from low permeability of the outer membrane (this is primarily important in Pseudomonas aeruginosa), and active efflux from the cell. Resistance to beta-lactam antibiotics, however, is primarily caused by the elaboration of an ever-growing number of beta-lactamases. Our ability to understand the genetic and biochemical underpinnings of these resistance phenotypes will be an important factor in determining the ultimate success of efforts to control their emergence and spread.

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“…5 From the clinical standpoint, metallo--lactamases are threatening resistant determinants due to their broadspectrum substrates, including carbapenems and mechanism-based -lactamase inactivators. 6 P. aeruginosa and other gram-negative rods are opportunistic pathogens and frequently cause severe infections in immunocompromised hosts. Because antimicrobial agents have become ineffective against carbapenem-resistant gram-negative rods, early detection and recognition of these resistant organisms are important for protection against their spread.…”

mentioning

confidence: 99%