en Anti-microbial agents, resistance and treatment protocols Anti-microbial agents, resistance and treatment protocols Original article Original article <p dir="ltr"><strong>Introduction:</strong> The major resistance mechanisms of <em>Pseudomonas aeruginosa</em> to fluoroquinolones and carbapenems are associated with the mutations in the genes <em>gyrA </em>and <em>oprD</em> encoding type II topoisomerases (DNA gyrase) and OprD porin, respectively. <strong>Method: </strong>In this cross-sectional study, sixty five clinical samples were collected from patients hospitalized in Al-Zahra Hospital of Isfahan, Iran. Susceptibility testing was performed by using disk diffusion and minimum inhibitory concentration (MIC) by E-test methods as recommended by Clinical Laboratory Standards Institute (CLSI). The assay was based on a DNA sequencing method using polymerase chain reaction (PCR).<strong> Results:</strong> The disk diffusion and E-test methods showed significant concordance in determining the in-vitro activity of the meropenem and ciprofloxacin against <em>P. aeruginosa</em> isolates. The mutations associated with antibiotic resistance were detected in the codon 83 of the <em>gyrA</em> gene, and various codons of the <em>oprD</em> gene. <strong>Conclusion: </strong>Our results showed that the main mechanism of fluoroquinolone resistance in <em>P. aeruginosa</em> is mediated primarily through mutations in <em>gyrA</em> and carbapenem resistance was driven mainly by the mutational inactivation of <em>oprD</em> gene.</p> P. aeruginosa, sequencing, gyrA and oprD 147 152 http://jommid.pasteur.ac.ir/browse.php?a_code=A-10-81-1&slc_lang=en&sid=1 Hossein Fazeli h-fazeli@med.mui.ac.ir No Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Hamid Solgi hamid.solgi@gmail.com Yes Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran Seyed Asghar Havaei havaei@med.mui.ac.ir No Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Dariush Shokri zamani.fz93@yahoo.com No Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Masoumeh Norouzi Barogh h.solgi196@yahoo.com No Department of Biochemistry & Genetics, Qazvin University of Medical Sciences, Qazvin, Iran Fateme Zahra Zamani h_solgi66@yahoo.com No School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran