Development of a broad-spectrum antimicrobial combination for the treatment of Staphylococcus aureus and Pseudomonas aeruginosa corneal infections [Experimental Therapeutics]

Staphylococcus aureus and Pseudomonas aeruginosa are two of the most common causes of bacterial keratitis and corresponding corneal blindness. Accordingly, such infections are predominantly treated with broad spectrum fourth generation fluoroquinolones, such as moxifloxacin. Yet rising fluoroquinolone resistance has necessitated the development of alternative therapeutic options. Herein we describe development of a polymyxin B/trimethoprim (PT) ophthalmic formulation containing the antibiotic rifampicin, which exhibits synergistic antimicrobial activity toward a panel of contemporary ocular clinical S. aureus and P. aeruginosa isolates, low spontaneous resistance frequency, and displays in vitro bactericidal kinetics and antibiofilm activities equaling or exceeding the antimicrobial properties of moxifloxacin. The PT + rifampicin combination also demonstrated increased efficacy in comparison to either commercial PT or moxifloxacin in a murine keratitis model of infection, resulting in bacterial clearance of 70% in animals treated. These results suggest that the combination PT and rifampicin may represent a novel antimicrobial agent in the treatment of bacterial keratitis.

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