title: Spread of Efflux Pump Overexpressing-Mediated Fluoroquinolone Resistance and Multidrug Resistance in Pseudomonas aeruginosa by using an Efflux Pump Inhibitor.
abstract: BACKGROUND
  Fluoroquinolone resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression and/or target mutations. We designed this study to investigate the efflux pump mediated fluoroquinolone resistance and check the increasing effectiveness of fluoroquinolones in combination with an efflux pumps inhibitor among P. aeruginosa isolates from burn wounds infections.
  
  
  METHODS
  A total of 154 consecutive strains of P. aeruginosa were recovered from separate patients hospitalized in a burn hospital, Tehran, Iran. The isolates first were studied by disk diffusion antibiogram for 11 antibiotics and then minimum inhibitory concentration (MIC) experiments were performed to detect synergy between ciprofloxacin and the efflux pump inhibitor, carbonyl cyanide-m-chlorophenyl hydrazone (CCCP). Then to elucidate the inducing of multi drug resistance due to different efflux pumps activation in Fluoroquinolone resistant isolates, synergy experiments were also performed in random ciprofloxacin resistant isolates which have overexpressed efflux pumps phenotypically, using CCCP and selected antibiotics as markers for Beta-lactams and Aminoglycosides. The isolates were also tested by polymerase chain reaction (PCR) for the presence of the MexA, MexC and MexE, which encode the efflux pumps MexAB-OprM, MexCD-OprJ and MexEF-OprN.
  
  
  RESULTS
  Most of the isolates were resistant to 3 or more antibiotics tested. More than half of the ciprofloxacin resistant isolates exhibited synergy between ciprofloxacin and CCCP, indicating the efflux pump activity contributed to the ciprofloxacin resistance. Also increased susceptibility of random ciprofloxacin resistant isolates of P. aeruginosa to other selected antibiotics, in presence of CCCP, implied multidrug extrusion by different active efflux pump in fluoroquinolones resistant strains. All of Ciprofloxacin resistant isolates were positive for MexA, MexC and MexE genes simultaneously.
  
  
  CONCLUSIONS
  In this burn hospital, where multidrug resistant P. aeruginosa isolates were prevalent, ciprofloxacin resistance and multidrug resistance due to the overexpression of fluoroquinolones mediated efflux pumps has also now emerged. Early recognition of this resistance mechanism should allow the use of alternative antibiotics and use an efflux pumps inhibitor in combination with antibiotic therapy.
authors.affiliation: Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Adabi
authors.affiliation: Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahshid
authors.initials: M
authors.lastname: Talebi-Taher
authors.affiliation: Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Arbabi
authors.affiliation: Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mastaneh
authors.initials: M
authors.lastname: Afshar
authors.affiliation: Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Fathizadeh
authors.affiliation: Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Minaeian
authors.affiliation: Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Moghadam-Maragheh
authors.affiliation: Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Majidpour
keywords: Antibiotic therapy; Burned patients; Ciprofloxacin, Carbonyl cyanide-m-chlorophenyl hydrazone; Efflux pump; Pseudomonas aeruginosa