Effect of sulbactam on anti-pseudomonal activity of beta-lactam antibiotics in cells producing various levels of the MexAB-OprM efflux pump and beta-lactamase

The beta -lactamase inhibitor, sulbactam, was tested for beta -lactamase in hibitory activity in Pseudomonas aeruginosa cells producing various levels of both the MexAB-OPrM efflux pump and beta -lactamase, We found that sulba ctam lowered the MICs of cefoperazone and piperacillin by inhibiting the be ta -lactamase 8-fold in the cell producing a constitutively high level of A mpC-type beta -lactamase and a wild-type level of MexAB-OprM pump compared with that without sulbactam, The MICs of cefoperazone and piperacillin in t he cell producing a constitutively high level of both the efflux pump and b eta -lactamase under the presence of sulbactam were 8 and 4 times, respecti vely, lower than that without sulbactam, The MICs of sulbactam in the cell producing a constitutively high and a wild-type level of the efflux pump we re 16- and 8-fold higher, respectively, than that in the mutant lacking the efflux pump, We concluded that sulbactam exerts potent beta -lactamase inh ibitory activity in the cell producing a high level of efflux pump, in spit e of the fact that sulbactam serves as a substrate of the MexAB-OprM pump. Increasing amounts of sulbactam over the weight of beta -lactams further st rengthen the effect of beta -lactam antibiotics.