First detected OXA-50 carbapenem-resistant clinical isolates from Bulgaria and interplay between the expression of main efflux pumps, OprD and intrinsic AmpC.

. Carbapenems are often described as the most effective weapon against infections caused by multidrug-resistant bacteria especially those belonging to the group of non-fermenting bacteria such as . The main mechanisms leading to resistance are the hyperexpression of certain efflux pumps belonging to the resisto-nodular division and the lower expression of the transmembrane porin OprD, sometimes in combination with excessive production of the intrinsic AmpC. Carbapenemases are assumed to play a secondary role. The aim of this study was to determine the exact mechanisms of carbapenem resistance in isolates from the largest Bulgarian University hospital 'St. George'- Plovdiv.. A total of 32 clinical isolates collected from different patients' samples resistant to imipenem and/or meropenem were examined via phenotypic and molecular-genetic tests.. No metallo-enzyme production was detected. Three isolates were positive for OXA-50-encoding genes in two of them in combination with other oxacillinases or the gene. For the first time, OXA-50-producing have been reported in Bulgaria. The increased expression or hyperexpression of MexXY-OprM efflux pump was observed as the main mechanism of resistance. In most cases, it was combined with lower expression or lack of OprD with or without MexAB-OprM hyperexpression. No excessive production of AmpC was detected in comparison to the reference ATCC 27853 . strain.. The increased expression or overexpression of MexXY-OprM efflux pumps is the leading cause of carbapenem resistance in our isolates , detected in 94 % of the bacteria investigated.