Origin and impact of plasmid-mediated extended-spectrum beta-lactamases

Resistance to oxyimino cephalosporins was originally highlighted by the emergence of plasmid-encoded extended-spectrum beta-lactamases deriving by mutation from TEM-1, TEM-2 and SHV type enzymes (class A). The broader spectrum of resistance produced by these enzymes is related to more amino acid substitutions, but susceptibility to seven alpha-methoxyimino cephalosporins and carbapenems was preserved until recently. Clavulanate-sensitive extended-spectrum beta-lactamases are distributed worldwide, mainly among Klebsiella pneumoniae isolates. Novel clavulanate-sensitive extended-spectrum beta-lactamases deriving from other class A enzymes (e.g. MEN-1 from beta la OXY, OXA-11 in Pseudomonas aeruginosa from PSE-2) have been reported. Recently, clavulanate-resistant extended-spectrum beta-lactamases (class C) were encountered amongst single isolates, mostly Klebsiella pneumoniae. These cephalosporinases or cefamycinases (usually chromosomally mediated) have expanded the spectrum of plasmid-encoded resistance to include seven alpha-methoxyimino cephalosporins. Thus far, only two isolates (1 Pseudomonas aeruginosa, 1 Bacteroides fragilis), both recovered in Japan, with plasmid-mediated resistance to carbapenems have been found.