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.

Objectives: 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.

Keywords: MIC; PDEi; antimicrobial susceptibility; ciprofloxacin; sildenafil; tadalafil; vardenafil.

Figure 1

The Escherichia coli DNA gyrase cleavage assay. DNA gyrase was incubated with supercoiled pBR322 in the presence of 0.1 µg/ML ciprofloxacin (CFX) and/or 1 of the phosphodiesterase inhibitors (100 µM). Bands were separated using 1% agarose and visualized using ethidium bromide. Phosphodiesterase inhibitors (100 µM) did not affect antigyrase activity of 0.1 µg/mL CFX.