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Ciprofloxacin-Induced Antibacterial Activity Is Attenuated by Phosphodiesterase Inhibitors.

Masadeh MM, Alzoubi KH, Khabour OF, Al-Azzam SI - Curr Ther Res Clin Exp (2014)

Bottom Line: 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.The results showed that PDEi drugs had no effect on ciprofloxacin's inhibition of E coli gyrase activity.Pretreatment of various reference bacterial cells with PDEis largely inhibited the antibacterial activity of ciprofloxacin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid, Jordan.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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f0005: 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.

Mentions: To examine the mechanism by which PDEis interfere with the action of ciprofloxacin, the in vitro E coli DNA gyrase cleavage assay was used. The results showed that ciprofloxacin significantly inhibited E coli gyrase activity. However, treatment with PDEi drugs had no effect on ciprofloxacin-induced inhibition of E coli gyrase activity (Figure 1). Moreover, PDEi drugs alone did not affect E coli gyrase activity (data not shown).


Ciprofloxacin-Induced Antibacterial Activity Is Attenuated by Phosphodiesterase Inhibitors.

Masadeh MM, Alzoubi KH, Khabour OF, Al-Azzam SI - Curr Ther Res Clin Exp (2014)

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.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644238&req=5

f0005: 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.
Mentions: To examine the mechanism by which PDEis interfere with the action of ciprofloxacin, the in vitro E coli DNA gyrase cleavage assay was used. The results showed that ciprofloxacin significantly inhibited E coli gyrase activity. However, treatment with PDEi drugs had no effect on ciprofloxacin-induced inhibition of E coli gyrase activity (Figure 1). Moreover, PDEi drugs alone did not affect E coli gyrase activity (data not shown).

Bottom Line: 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.The results showed that PDEi drugs had no effect on ciprofloxacin's inhibition of E coli gyrase activity.Pretreatment of various reference bacterial cells with PDEis largely inhibited the antibacterial activity of ciprofloxacin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid, Jordan.

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.

No MeSH data available.


Related in: MedlinePlus