Tuesday, November 15, 2011

Pseudomonas aeruginosa resistant to carbapenems

Ps. aeruginosa is an opportunistic pathogen that can cause severe invasive disease in critically ill and immunocompromised patients. This microorganism is an important cause of nosocomial infections, including pneumonia, wound infections, bacteremia and urinary tract infection (Ceza´ rio et al., 2009). The organism has both an intrinsic and acquired resistance to many antimicrobials and treatment of infection by this organism is difficult. Carbapenems have a high potency against a wide range of organisms and are one of the most active groups of β-lactam antibiotics against Ps. aeruginosa (Sakyo et al., 2006). 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 by mutation 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 to multiple agents, including all β-lactams (meropenem is a substrate of efflux pumps whereas imipenem is not due to the absence of heterocyclic side chain), fluoroquinolones, and aminoglycosides. MexA-MexB-OprM is regarded the most efficient efflux pump for extrusion of carbapenems. 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 MBL, particularly IMP and VIM enzymes, which are able to hydrolyze efficiently all β-lactams with the exception of aztreonam (Gutierrez et al., 2007). Although majority of calss A serine carbapenemases are found in Enterobacteriaceae family members, but resistance may transfer through mobile genetic elements to other families such as GES enzyme which may be found as cassettes within integrons on plasmid mostly in Ps. aeruginosa (Overturf, 2010).

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