The overexpression of the MexAB-OprM and MexXY-OprM efflux systems were more frequent among antimicrobial resistant P. aeruginosa isolates. Since MexAB-OprM and MexXY-OprM are constitutively expressed in wild type P. aeruginosa isolates, the antimicrobial policy in use in each individual institution may interfere with the selection of Blebbistatin the most overexpressed efflux system. Aminoglycosides are important substrates of MexXY-OprM and might have exerted a role in selecting P. aeruginosa that overexpressed this system . The expression
of MexXY-OprM is inducible, while expression of MexAB-OprM is not . In our institution, the prescription of aminoglycosides is not controlled and these antimicrobial agents usually are prescribed in combination for treatment of P. aeruginosa infections. These facts could in part justify why MexXY-OprM was the most frequent
overexpressed efflux system, since mexXY expression may be induced by these antimicrobial class . Interestingly, the overexpression of MexXY-OprM was observed in all MBL-producing isolates. We did not notice a strict correlation between antimicrobial resistance and efflux genes overexpression. However, efflux overexpressing isolates often presented higher antimicrobial MICs than did PAO1 and those isolates in which no antimicrobial resistance determinant was found. Our findings clearly demonstrate that β-lactamase production increase antimicrobial MICs more efficiently than do efflux overexpression or porin down-regulation alone. However, these chromosomal resistance mechanisms were frequently present among acquired β-lactamase producers. Selleckchem Batimastat These findings suggest that efflux overexpression and porin down-regulation may favor the AG-120 Bacterial survival
under selective pressure, increasing its chance to acquire further resistance determinants. In the present study we have observed that efflux pump overexpression do not appear to be the main mechanism of drug resistance among the studied clinical isolates of P. aeruginosa, but represents an adjuvant mechanism for antimicrobial resistance. The association of distinct mechanisms such as the porin down-regulation and AmpC overproduction play also an important role in the multi-drug resistance phenotype among P. aeruginosa clinical isolates Carnitine palmitoyltransferase II studied. In addition, our findings indicate that spread of clones and emergency of distinct genotypes have occurred in our institution and implementation of control measures is extremely necessary to modify this scenario. Methods Bacterial isolates and antimicrobial susceptibility testing With the approval of the local Ethics in Research committee (Comitê de Ética em Pesquisa Hospital São Paulo, protocol number: CEP0398/07), a total of 59 clinical isolates of P. aeruginosa were evaluated, regardless of their antimicrobial susceptibility profile.