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Background: Pseudomonas aeruginosa is a leading cause of nosocomial infections worldwide. Resistance of P. aeruginosa strains to the broad-spectrum cephalosporins may be caused by extended-spectrum β-lactamases (ESBLs)., Objectives: The aim of this study was to determine the antimicrobial resistance patterns and prevalence of PER-1 and VEB-1 type genes among ESBL producing strains of P. aeruginosa., Material and Methods: A total of 106 P. aeruginosa isolates were collected from two university hospitals in Hamadan, Iran, during a7-month study (2009). The antimicrobial susceptibility of isolates was determined by disc diffusion method and interpreted according to the clinical and laboratory standards institute (CLSI) recommendations. Production of ESBL was determined by combined disk test and presence of PER-1 and VEB-1 type ESBL genes was identified by PCR., Results: The resistance against broad-spectrum cephalosporins and monobactames were: cefepime (97%), cefotaxime (92.5%) ceftazidime (51%), and aztreonam (27%). Ciprofloxacin (91.5%), imipenem (84.9%) and meropenem (82.1%) were the most effective anti-pseudomonas agents in this study. The results revealed that 88.7% of the isolates were multidrug resistant, 58.25% of those were ESBL positive. Sixteen (26.6%), 9 (15%) and 3 (5%) strains among ESBL-producing strains contained blaPER-1, blaVEB and blaPER-1-blaVEB, respectively., Conclusions: This study highlighted the need to establish antimicrobial resistance surveillance networks for P. aeruginosa to determine the appropriate empirical treatment regimens. The high prevalence of multidrug resistance and production of ESBLs in P. aeruginosa isolates confirms the necessity of protocols considering these issues in the hospitals.