Pseudomonas aeruginosa--a significant hospital pathogen and resistance to carbapenem

Pseudomonas aeruginosa (P. aeruginosa) is an etiologic agent of nosocomial infections of various localizations. The frequency of infections is a consequence of an increased number of immunocompromised patients, large surgical interventions, long-term hospital care and virulence factors of the bacterium. The use of carbapenems in the treatment of infections caused by P. aeruginosa and other gram-negative bacteria entail an unfortunate consequence of creating resistance to carbapenems. P. aeruginosa exhibits numerous mechanisms of resistance and is singularly problematic for combining intrinsic resistance and acquired resistance due to multiple mutations. It is also a carrier of the multiple-resistance plasmide. Carbapenems are a class of beta-lactam antibiotics with broad-spectrum activity to gram-positive, gram-negative and strictly anaerobic bacteria. The resistance of P. aeruginosa to carbapenems is complex and heterogeneous. It is determined by weakening the penetration through the outer membrane due to the loss of porin D2, decrease in the accumulation of antibiotic in the cell consequentially to active efflux due to hyperproduction of proteins, hydrolysis of carbapenem by specific metallo-beta-carbapenemases, and alteration in the target area of antibiotic activity on the bacterial cell. The loss of porin D2 results in resistance to imipenem with MIC values of 8.0-32.0 microg/mL. Selective low-level resistance to meropenem in the hyperproduction of the efflux system results in MIC values of 2.0-4.0 microg/mL. A high-level resistance to carbapenems with MIC values above 128 microg/mL for imipenem and meropenem is a consequence of the secretion of IMP and VIM series beta-carbapenemases. The frequency of resistance to P. aeruginosa to carbapenems varies worldwide from 15% to > or = 35%. In Croatia, resistance to carbapenems in the year 2003 was estimated to 12%. The problems in clinical practice are the increased resistance of P. aeruginosa to carbapenems, the presence of beta-carbapenemases and acquisition of these enzymes in certain types of Enterobacteriacea. The problems in laboratory practice are those of precise determination of the level and phenotype resistance of P. aeruginosa to carbapenems.