title: Interaction of methylxanthines and gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa: role of phosphodiesterase inhibition.
abstract: Previous studies showed that methylxanthines increased the antimicrobial activity of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa. In this study, the effect of non-selective phosphodiesterase (PDE) inhibitors (methylxanthines: aminophylline and caffeine) and partially selective PDE inhibitors, dipyridamole and sildenafil, was evaluated on the antimicrobial activity of gentamicin using checkerboard method. Aminophylline at concentrations of 0.5 and 1 mg/ml reduced the minimal inhibitory concentration (MIC) of gentamicin (2 μg/ml) 2 and 4 times against S. aureus, and at concentrations of 0.5 and 2 mg/ml reduced the MIC of gentamicin (4 μg/ml) 2 and 4 times, respectively, against P. aeruginosa. Caffeine at concentrations of 1 and 2 mg/ml reduced the MIC of gentamicin (2 μg/ml) 4 and 32 times against S. aureus, and at concentrations of 0.12 and 2 mg/ml reduced the MIC of gentamicin (4 μg/ml) 2 and 4 times, respectively, against P. aeruginosa. However, dipyridamole and sildenafil (32 μg/ml) did not show any effect on MIC of gentamicin against S. aureus and P. aeruginosa. These results suggest that methylxanthines could increase gentamicin effects against S. aureus and P. aeruginosa but this effect is not mediated by inhibition of PDE 5, 6, 8, 10 and 11.
authors.affiliation: Mashhad University of Medical Sciences Biotechnology Research Center, School of Pharmacy Mashhad Iran.
authors.forename: Bibi Sedigheh Fazly
authors.initials: BS
authors.lastname: Bazzaz
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Lavaei
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinzadeh
mesh_terms: D000628:Aminophylline / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D004347:Drug Interactions; D005839:Gentamicins / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010726:Phosphodiesterase Inhibitors; D000628:Aminophylline; D002110:Caffeine