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EJ Lee, TN Truong, MN Mendoza, SM J Fleiszig; Therapies Used for Treating Human Pseudomonas aeruginosa Corneal Infection Have Little Effect on Disease Progression in an Animal Model . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1587.
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Purpose: Pseudomonas aeruginosa keratitis can be devastating even when treated aggressively with conventional topical antibiotics. There are two types of P. aeruginosa that cause keratitis; the invasive strain type can reside within corneal epithelial cells. The aim of this study was to determine whether the cell-permeable antibiotic ofloxacin was more effective than the cell-impermeable antibiotic tobramycin at reducing disease caused by invasive strains. Methods: The left corneas of C57BL/6 mice were scratched with a needle and allowed to heal for 6h before topical inoculation (∼108 cfu in 5 microliter) with either P. aeruginosa strain 6206 (cytotoxic) or PA01 (invasive). At 3, 6, or 12h post-inoculation, treatment with phosphate buffered saline (PBS), prednisolone acetate (1%), tobramycin (0.3%), or ofloxacin (0.3%) was initiated and continued hourly for 12h. The effect of antibiotic/steroid combination treatment (prednisolone acetate with either ofloxacin or tobramycin) was also explored. Corneas were graded and photodocumented prior to and after the treatment period. Viable counts of bacteria in whole eyes were also performed at the end of the treatment period. Results: Ofloxacin was no more effective than tobramycin for either PA01 or 6206. Interestingly, neither antibiotic was more effective than PBS or prednisolone at reducing the severity of disease, although both drugs dramatically reduced the number of viable bacteria in corneas. For all four monotherapeutic regimens, disease progression occurred when treatments were begun 6 or 12h post-inoculation, but not at 3h. Antibiotic/steroid combination treatment outcome was no more effective than monotherapy with antibiotics. Conclusion: In a murine infection model, elimination of bacteria with antibiotic therapy, as is dictated by conventional protocol, did not improve clinical outcome, even when treatment was initiated very early during the infectious process. The addition of topical corticosteroid therapy was of little value. Since the pathogenesis of infection is a complex interplay between bacterial and host factors, a therapeutic regimen that takes into account multiple aspects of infection may be more effective.
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