Cefotaximases (CTX-M-ases), an expanding family of extended-spectrum beta-lactamases.
Among the extended-spectrum beta-lactamases, the cefotaximases (CTX-M-ases) constitute a rapidly growing cluster of enzymes that have disseminated geographically. The CTX-M-ases, which hydrolyze cefotaxime efficiently, are mostly encoded by transferable plasmids, and the enzymes have been found predominantly in Enterobacteriaceae, most prevalently in Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Proteus mirabilis. Isolates of Vibrio cholerae, Acinetobacter baumannii, and Aeromonas hydrophila encoding CTX-M-ases have also been reported. The CTX-M-ases belong to the molecular class A beta-lactamases, and the enzymes are functionally characterized as extended-spectrum beta-lactamases. This group of beta-lactamases confers resistance to penicillins, extended-spectrum cephalosporins, and monobactams, and the enzymes are inhibited by clavulanate, sulbactam, and tazobactam. Typically, the CTX-M-ases hydrolyze cefotaxime more efficiently than ceftazidime, which is reflected in substantially higher MICs to cefotaxime than to ceftazidime. Phylogenetically, the CTX-M-ases are divided into four subfamilies that seem to have descended from chromosomal beta-lactamases of Kluyvera spp. Insertion sequences, especially ISEcp1, have been found adjacent to genes encoding enzymes of all four subfamilies. The class I integron-associated orf513 also seems to be involved in the mobilization of blaCTX-M genes. This review discusses the phylogeny and the hydrolytic properties of the CTX-M-ases, as well as their geographic occurrence and mode of spread.
Walther-Rasmussen
Jan
J
Deparment of Clinical Microbiology, The National University Hospital, Copenhagen, Denmark. jawalras@mail.tele.dk
Høiby
Niels
N
D002439:Cefotaxime / Q000378:metabolism*; D002511:Cephalosporins / Q000378:metabolism; D019818:Clavulanic Acid / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022761:Gene Transfer, Horizontal; D008997:Monobactams / Q000378:metabolism; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010406:Penicillins / Q000378:metabolism; D010802:Phylogeny; D013407:Sulbactam / Q000494:pharmacology; D000078142:Tazobactam; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism*
D002511:Cephalosporins; D004791:Enzyme Inhibitors; D008997:Monobactams; D010406:Penicillins; D019818:Clavulanic Acid; D010397:Penicillanic Acid; C071167:beta-lactamase CTX-2; D001618:beta-Lactamases; D002439:Cefotaxime; D013407:Sulbactam; D000078142:Tazobactam