[Mechanisms of pandrug-resistance of Pseudomonas aeruginosa].

OBJECTIVE

To explore the mechanisms of pandrug-resistance (PDR) of Pseudomonas aeruginosa (PA).

METHODS

Nineteen strains of PA were collected from Huashan Hospital, Shanghai. Agar dilution method was used to detect the levels of minimum inhibitory concentration (MIC) of 14 antimicrobial drugs to the PA strains. Strain homology was investigated by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). To analyze the beta-lactam resistant mechanisms, genes of extended-spectrum beta-lactamases (ESBLs), carbapenemase, and plasmid-mediated AmpC were amplified and analyzed by PCR and DNA sequencing. To analyze the aminoglycoside resistant mechanisms, 16 aminoglycoside modifying enzyme were screened by PCR. PCR and DNA sequencing were used to amplify and analyze the genes of DNA gyrase genes gyrA and gyrB, topoisomerase IV genes parC and pare, and qnr gene for the fluoroquinolone resistance mechanisms, to amplify and analyze study the oprD2 coding genes and inhibitor MC207110 were used to detect efflux pump for the carbapenem resistance mechanisms.

RESULTS

Five types were identified in the 19 PDR-PA by ERIC-PCR, mainly type A (n=6) and type B (n=7). 17 of the 19 PDR-PA strains produced VEB-3 type ESBL, 1 strain of which also produced OXA-10 type ESBL simultaneously. Both of the carbapenemase and plasmid-mediated AmpC were negative. All of the 19 PDR-PA strains produced aminoglycoside modifying enzyme, yielding ant (3") I and 18 strains of which produced aac (3) II simultaneously. All 19 PDR-PA strains carried gyrA mutations, 14 of which carried parC mutation simultaneously, qnr gene was negative. OprD2 coding gene sequencing analysis revealed that small fragment missing occurred to all oprD2 genes of the 19 strains. 16 strains showed efflux pump mechanism.

CONCLUSION

The resistance mechanism of PDR-PA to cephalosporins, beta-lactam/beta-lactamase inhibitor, carbapenem, fluoroquinolones, and aminoglycosides are due to production of VEB-3-ESBL, aac (3) II, and ant (3") I aminoglycoside modifying enzyme, mutations of DNA gyrase gyrA and topoisomerase parC gene, OprD2 protein deficiencies, and efflux pump overexpression.