Caracterización de los mecanismos de resistencia de aislamientos clínicos de Pseudomonas aeruginosa no sensibles a carbapenems y factores de riesgo asociados a su adquisición

Abstract

The epidemiology-related features of antibiotic resistant Pseudomonas aeruginosa strains (Pa) isolated in the University Hospital of Navarra from January 2002 to February 2009 were analyzed. An increase of Pa isolates not susceptible to carbapenems (Pa-nsc) was detected and the profile of antibiotic resistance of these organisms was markedly different from that of carbapenem susceptible Pa (Pasc). Both Pa-nsc and the overall Pa isolates increased their resistance to several antibiotic classes, whereas Pa-sc maintained their level of susceptibility. Phenotypic methods most commonly used for detection of metallo-beta-lactamase producing strains (MBL) including E-test MBL, simple microdilution test, double disk synergy test and disks combined test were compared and found to render 100% sensitivity. The combined disk test using imipenem and EDTA provided the greatest specificity. The susceptibility to doripenem in Pa isolates not susceptible to imipenem and meropenem was analyzed. Depending on the cut-off points established by CLSI, EUCAST and FDA, it was found that 28.6% to 11.9% of the strains not susceptible to imipenem were susceptible to doripenem, while 26.2% to 10.7% of strains not susceptible to meropenem were susceptible to doripenem. The mechanisms of resistance to carbapenems in clinical isolates of Pa-nsc were characterized. The altered expression of the porin OprD was the most common resistance mechanism (87.5%), followed by the overproduction of AmpC (33.3%). Four MBL-producing strains of the VIM-2 family were detected including the first MBL-producing strain sensitive to doripenem (MIC 1 ì/ml). The use of urinary catheter and the consumption of broad-spectrum antibiotics (piperacillin-tazobactam, carbapenems, fluoroquinolones and aminoglycosides) were established as risk factors for the acquisition of Pa-nsc. Exposure to hospital environment and the use of mechanical ventilation were identified as risk factors when the groups under comparison were Pa-nsc isolates versus isolates different from Pa. Finally, a prolonged hospital admission, the isolation of multiresistant Pa, the administration of chemotherapy and the use of immunosuppressive drugs were predictors of mortality attributable to Pa-nsc.