title: Ciprofloxacin-Induced Antibacterial Activity Is Attenuated by Phosphodiesterase Inhibitors.
abstract: BACKGROUND
  Ciprofloxacin is a commonly used antibiotic for urinary tract infection that interacts with bacterial topoisomerases leading to oxidative radicals generation and bacterial cell death. Phosphodiesterase inhibitors (PDEis), on the other hand, are commonly used drugs for the management of erectile dysfunction. The group includes agents such as sildenafil, vardenafil, and tadalafil.
  
  
  OBJECTIVE
  We investigated whether PDEi could interfere with the antibacterial activity of ciprofloxacin.
  
  
  METHODS
  PDEis were tested in several reference bacteria, including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis, and Klebsiella pneumoniae utilizing a standard disc diffusion method and measuring both zones of inhibition and MIC.
  
  
  RESULTS
  Results from both assays indicated that ciprofloxacin demonstrates potent activity against the tested reference bacteria. Additionally, when bacteria were treated with a combination of ciprofloxacin and sildenafil, tadalafil, or vardenafil, the zones of the combination inhibition were significantly reduced, whereas the MIC values were significantly greater than those of ciprofloxacin alone for all tested bacterial strains. In an attempt to examine the mechanism by which PDEis interfere with the action of ciprofloxacin, we utilized the in vitro E coli DNA gyrase cleavage assay. The results showed that PDEi drugs had no effect on ciprofloxacin's inhibition of E coli gyrase activity.
  
  
  CONCLUSIONS
  Pretreatment of various reference bacterial cells with PDEis largely inhibited the antibacterial activity of ciprofloxacin.
authors.affiliation: Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Majed M
authors.initials: MM
authors.lastname: Masadeh
authors.affiliation: Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Karem H
authors.initials: KH
authors.lastname: Alzoubi
authors.affiliation: Department of Biology, Faculty of Science, Taibah University, Medina, Saudi Arabia ; Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Omar F
authors.initials: OF
authors.lastname: Khabour
authors.affiliation: Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Sayer I
authors.initials: SI
authors.lastname: Al-Azzam
keywords: MIC; PDEi; antimicrobial susceptibility; ciprofloxacin; sildenafil; tadalafil; vardenafil