Biological efficacy and stability of diluted ticarcillin-clavulanic acid in the topical treatment of Pseudomonas aeruginosa infections

Topical compounded Timentin® diluted with an inactive vehicle has been reported to be effective in the treatment of otitis externa caused by Pseudomonas aeruginosa. The aims of this study were to determine the biological efficacy of Timentin® (ticarcillin and clavulanic acid) when diluted in the carrier vehicle Methopt® against P. aeruginosa and to determine the efficacy and stability of Timentin® aqueous stock concentrate solution. Timentin® stock concentrate was tested against four P. aeruginosa isolates on days 0, 7, 14, 21 and 28; then after 2, 3, 4, 5, 6, 9 and 12 months of storage at 4 or −20°C. The diluted Timentin®–Methopt® solutions were tested against all isolates after 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 and 28 days of storage at 24 or 4°C. Minimal inhibitory concentration (MIC) levels for all strains were determined using the broth microdilution method. The MIC of the stock solution remained relatively constant and acceptable throughout the study when stored at −20°C and was also acceptable for shorter time periods (6–9 months) when stored at 4°C. The MIC for the diluted Timentin®–Methopt® solution remained relatively constant and acceptable throughout the study for all four bacterial strains, with no difference between the solutions stored at 4 or 24°C. The results of this study indicate that storage of the Timentin® stock solution at −20°C does not compromise efficacy for at least 12 months and that Timentin® diluted in Methopt® was stable for 28 days when stored at either 4 or 24°C. Résumé Le Timentin®, composé topique, dilué dans un véhicule inactivé, a été rapporté comme actif dans le traitement de l’otite externe àPseudomonas aeruginosa. Les objectifs de cette étude étaient de déterminer l’efficacité biologique contre Pseudomonas aeruginosa du Timentin® (ticarcilline/acide clavulanique) dilué dans du Methopt® et de déterminer l’efficacité et la stabilité de la solution mère aqueuse concentrée de Timentin®. La solution mère de Timentin a été testée contre quatre isolats de P. aeruginosaà jours 0, 7, 14, 21, 28 et après 2, 3, 4, 5, 6, 9 et 12 mois de stockage à 4°C et −20°C. Les solutions diluées de Timentin®/Methopt® ont été testées contre tous les isolats après 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 et 28 jours de stockage à 24°C et 4°C. Les niveaux de concentration minimale inhibitrice (MIC) pour toutes les souches ont été déterminés par microdilution en milieu liquide. La MIC de la solution mère est restée relativement constante au cou