Saturday, August 27, 2011

Resistance to carbapenems

Carbapenems are commonly used as last resort drugs for treatment of infections caused by multiresistant Ps. aeruginosa isolates. Carbapenem resistance was driven mainly by mutation mediated resistance leading to the repression or inactivation of the porin OprD, conferring resistance to imipenem and reduced susceptibility to meropenem (Quale et al., 2006), and those leading to the hyperexpression of the chromosomally encoded cephalosporinase AmpC. Also remarkable, mutations leading to the up-regulation of one of the several efflux pumps encoded in the Ps. aeruginosa genome may confer resistance or reduced susceptibility to multiple agents, including all ╬▓-lactams (except imipenem), fluoroquinolones, and aminoglycosides. Furthermore, the accumulation of various combinations of these chromosomal mutations can certainly lead to the emergence of multidrug resistant (Cavallo et al., 2007).
In addition to the mutation-mediated resistance, the presence of horizontally acquired resistance determinants in Ps. aeruginosa has been increasingly reported over the last decade. Among the certainly noteworthy determinants are those encoding metallo╬▓-lactamases, particularly IMP and VIM enzymes, which are able to hydrolyze efficiently all ╬▓-lactams with the exception of aztreonam (Gutierrez et al., 2007).

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