Mechanisms and detection of carbapenem resistance in Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii

Numerous mechanisms of resistance to the carbapenems have been described in Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Resistance to this class of agents can be divided into three main categories that include β-lactamases, efflux pumps, and changes in outer membrane porin proteins. Scant reports have also implicated penicillin-binding protein alterations in A. baumannii and P. aeruginosa. Inactivation of the carbapenems can be accomplished by a variety of β-lactam hydrolysing enzymes. The IMP and VIM metallo-carbapenemases, belonging to the molecular class B family, are the most worrisome of all β-lactamases because they confer resistance to the carbapenems and all other β-lactam agents with the exception of aztreonam. Several molecular class A, C and D β-lactamases have also demonstrated carbapenem hydrolysing activity but are less efficient in their capability. Efflux pumps, especially in P. aeruginosa, usually enhance resistance mediated by other mechanisms. Alterations in outer membrane porin proteins prevent or impede carbapenem penetration and subsequent binding to their targets in P. aeruginosa, K. pneumoniae, and A. baumannii. Finally, two or more of these mechanisms have been shown to act in concert to produce clinical resistance to carbapenems. Since expression of these mechanisms may be subtle, detection of carbapenem resistance in the clinical microbiology laboratory can be problematic.