The effectiveness of an improved combination therapy for experimental Staphylococcus aureus keratitis

• Published in: Advances in therapy 2010-12, Vol.27 (12), p.933-940
• Main Authors: Balzli, Charles L., McCormick, Clare C., Caballero, Armando R., Tang, Aihua, O’Callaghan, Richard J.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Cardiology; Colony Count, Microbial; Cornea - drug effects; Dexamethasone - administration & dosage; Disease Models, Animal; Drug Therapy, Combination; Endocrinology; Eye Infections, Bacterial - drug therapy; Health technology assessment; Internal Medicine; Keratitis - drug therapy; Keratitis - microbiology; Medicine; Medicine & Public Health; Oncology; Original Research; Pharmacology/Toxicology; Polysaccharides, Bacterial - administration & dosage; Prednisolone - administration & dosage; Pseudomonas Infections - drug therapy; Rabbits; Rheumatology; Staphylococcus aureus; Tobramycin - administration & dosage
• ISSN: 0741-238X; 1865-8652
• DOI: 10.1007/s12325-010-0082-x

Introduction Antibiotic and steroid combination therapies, such as tobramycin with dexamethasone, are often used in ophthalmology to treat or prevent infection and inflammation. The purpose of this study was to use a model of Staphylococcus aureus keratitis to quantify and compare the effectiveness of a standard tobramycin and dexamethasone combined therapy, with each drug individually, and with a new formulation of the two drugs in a xanthan gum vehicle. Methods Rabbit corneas were intrastromally injected with a methicillin-sensitive S. aureus (MSSA) or a methicillin-resistant S. aureus (MRSA) strain. Rabbit eyes were treated every hour from 10 to 15 hours postinfection (PI) with 0.1% dexamethasone, 0.3% tobramycin, 0.3% tobramycin with 0.1% dexamethasone, or 0.3% tobramycin with 0.05% dexamethasone in a xanthan gum vehicle (ST). Slit lamp examinations (SLE) were performed on infected eyes and pathology scored at 15 hours PI. At 16 hours PI, colony forming units (CFUs) per cornea were quantified. Results The CFUs in eyes treated with dexamethasone alone were similar to untreated control eyes for MSSA or MRSA infections. All other treatment groups had significantly less CFUs per cornea than untreated eyes. The eyes treated with the ST formulation had significantly fewer CFUs per cornea than all other treatment groups when infected with MSSA or MRSA. The SLE scores of MSSA or MRSA infected eyes treated with tobramycin alone were similar to untreated control eyes. All other treatment groups had significantly lower SLE scores than untreated controls eyes, but were not significantly different from each other. Conclusion The results of this study demonstrated that the tobramycin and dexamethasone combination therapy with a xanthan gum vehicle has an improved bactericidal effectiveness compared to the commercially available formulation, and maintains a similar anti-inflammatory effect while containing half the amount of steroid.