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.