Adrenal Cortex Hormones / pharmacology ; Adrenal Cortex Hormones / therapeutic use ; Anti-Bacterial Agents / pharmacology ; Anti-Bacterial Agents / therapeutic use ; Bacteria ; Dexamethasone / pharmacology ; Dexamethasone / therapeutic use ; Drug Combinations ; Eye Infections, Bacterial* / drug therapy ; Eye Infections, Bacterial* / microbiology ; Fluorometholone / pharmacology ; Fluorometholone / therapeutic use ; Humans ; Keratitis* / drug therapy ; Levofloxacin / pharmacology ; Levofloxacin / therapeutic use ; Prednisolone / pharmacology ; Prednisolone / therapeutic use ; Tobramycin / pharmacology ; Tobramycin / therapeutic use
Abstract
Purpose: Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted.
Methods: Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells.
Results: The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations.
Conclusions: Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration.
Translational relevance: When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.