Resistance to Different Antibiotics
Ps. aeruginosa is a leading cause of nosocomial infection in critically ill patients and is associated with the highest attributable mortality among opportunistic Gram-negative bacteria. It is intrinsically resistant to most β-lactam antibiotics, tetracyclines, chloramphenicol, sulfonamides and nalidixic acid, due to the interplay of impermeability with multidrug efflux, principally mediated by MexAB-OprM. Acquired resistance to anti-pseudomonal antibiotics develops rapidly in more than 10% of patients during treatment. This occurs most commonly with imipenem and ciprofloxacin. Multiple types of acquired β-lactam resistance are expressed by this adaptable organism, often in combination: hyperproduction of AmpC cephalosporinase, acquisition of transposon and plasmid-mediated ESBLs, oxacillinases or carbapenemases; mutational loss of porins or upregulation of efflux pumps. Three types of aminoglycoside resistance are seen: highlevel, plasmid-mediated resistance to one or two aminoglycosides, due to the production of aminoglycoside-modifying enzymes, and broad-spectrum resistance to all the aminoglycosides, due to a reduction in the permeability of the cell envelope and/or overexpression of an efflux pump. Fluoroquinolone resistance is mediated by topoisomerase gene mutations, decreased permeability and efflux overexpression.
Only 10 years after the first description of VIM-1 in a Ps. aeruginosa isolate in 1997, the VIM-2 variant has become the most widespread metallo-β-lactamase (MBL) among Ps. aeruginosa strains.101 VIM-producing strains have caused hospital outbreaks worldwide. IMP enzymes have also been reported in this organism. The blaIMP and blaVIM genes are inserted into class 1 integrons. Other mobile genes encoding MBL enzymes were reported in Ps. aeruginosa, including the SMP (endemic in Brazil) and GIM (reported in Germany) enzymes.101 These carbapenemase-producing Ps. aeruginosa strains are multiresistant and on many occasions susceptible to colistin only. Class A β-lactamases such as VEB have been described with increasing frequency in this organism, whereas the GES and KPC enzymes were found in Latin America.101 Multiresistant Ps. aeruginosa is becoming one of the most problematic nosocomial pathogens, particularly in view of the lack of new antimicrobial classes in clinical development that are active on this organism.
