Which Mex efflux pumps are overexpressed in multidrug-resistant Pseudomonas aeruginosa?

Abstract number: o125

Hocquet  D., Fabre  R., Roussel-Delvallez  M., Cavallo  J.D., Dehecq  B., Plésiat  P.

Objectives: 

b-lactams (bLs), aminoglycosides (AGs) and fluoroquinolones (FQs) are substrates for one or several RND efflux pumps (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY/OprM) in Pseudomonas aeruginosa. The aim of this study was to determine the prevalence of these efflux mechanisms in resistant clinical strains of P. aeruginosa.

Methods: 

A hundred and seventy strains of P. aeruginosa with reduced susceptibility to ticarcillin (MIC > or = 32 mg/l) collected in 15 French hospitals in 2004 were analysed for the overexpression of efflux genes mexB, mexC, mexE and mexY, by real-time RT-PCR. MICs of antibiotics were determined by using the conventional agar dilution method.

Results: 

59% (n = 100), 65% (n = 110), 0.5% (n = 1) and 0.5% (n = 1) of the selected isolates were found to overproduce MexAB-OprM, MexXY, MexCD-OprJ, or/and MexEF-OprN, respectively. 59% (61/103) of the strains resistant to both ticarcillin and ciprofloxacin (MIC >= 2 mg/l overexpressed MexAB-OprM. 78% (69/88) and 83% (86/103) of the bacteria resistant to amikacin (MIC >= 8 mg/l) or ciprofloxacin exhibited up-regulation of MexXY, respectively. Interestingly, 48% (49/103) of the strains that were non susceptible to ciprofloxacin overproduced both MexAB-OprM and MexXY. The prevalence of the MexXY mechanism was correlated with the levels of resistance to ciprofloxacin (39, 50, 64, 89, 93 and 100% of the strains with MIC of ciprofloxacin of 2, 4, 8, 16, 32 and >= 64 mg/l were MexXY-overproducers, respectively) and to amikacin (17, 37, 58, 68, 76, 100, 80 and 93 % of the strains with MIC of amikacin of 1, 2, 4, 8, 16 and >= 32 mg/l).

Conclusion: 

These results show that in contrast to MexCD-OprJ and MexEF-OprN, the systems MexAB-OprM and MexXY/OprM are frequently up-regulated among clinical P. aeruginosa isolates showing decreased susceptibilities to bLs, AGs and/or FQs. Furthermore, drug efflux mediated by MexXY/OprM is highly prevalent in isolates with strong levels of resistance to AGs or FQs.