Emerging carbapenemases in Gram-negative aerobes.
Carbapenemases may be defined as beta-lactamases that significantly hydrolyze at least imipenem or/and meropenem. Carbapenemases involved in acquired resistance are of Ambler molecular classes A, B, and D. Class A, clavulanic acid-inhibited carbapenemases are rare. They are either chromosomally encoded (NMC-A, Sme-1 to Sme-3, IMI-1) in Enterobacter cloacae and Serratia marcescens, or plasmid encoded, such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa, the latter being a point-mutant of the clavulanic acid-inhibited extended-spectrum beta-lactamase GES-1. The class B enzymes are the most clinically significant carbapenemases. They are metalloenzymes of the IMP or VIM series. They have been reported worldwide but mostly from South East Asia and Europe. Metalloenzymes, whose genes are plasmid and integron located, hydrolyze virtually all beta-lactams except aztreonam. Finally, the class D carbapenemases are increasingly reported in Acinetobacter baumannii but compromise imipenem and meropenem susceptibility only marginally. The sources of the acquired carbapenemase genes remain unknown, as does the relative importance of the spread of epidemic strains as opposed to the spread of plasmid- or integron-borne genes. Because most of these carbapenemases confer only reduced susceptibility to carbapenems in Enterobacteriaceae, they may remain underestimated as a consequence of the lack of their detection.
Nordmann
P
P
Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris and Faculté de Médecine Paris-Sud, Université Paris XI, Paris, France. nordmann.patrice@bct.ap-hop-paris.fr
Poirel
L
L
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D019818:Clavulanic Acid / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006088:Gram-Negative Aerobic Bacteria / Q000201:enzymology*; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010405:Penicillinase / Q000145:classification; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D019818:Clavulanic Acid; D011494:Protein Kinases; C064979:IME2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D010405:Penicillinase; C417264:VIM-1 metallo-beta-lactamase; C409201:beta-lactamase IMP-1; D001618:beta-Lactamases; C063912:carbapenemase; C108449:oxacillinase