A worrisome trend in the study and treatment of infectious disease noted in recent years is\nthe increase in multidrug resistant strains of bacteria concurrent with a scarcity of new antimicrobial\nagents to counteract this rise. This is particularly true amongst bacteria within the Enterococcus\nfaecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa,\nand Enterobacter species (ESKAPE) designation. P. aeruginosa is one of the most common causes\nof bacterial keratitis. Therefore, it is of vital importance to characterize new antimicrobial agents\nwith anti-Pseudomonal activity for use with the ocular surface. MEDI3902 is a multifunctional\nantibody that targets the P. aeruginosa persistence factor Psl exopolysaccharide, and the type 3 secretion\nprotein PcrV. We initially assessed this antibody for ocular surface toxicity. The antimicrobial activity\nof the antibody was then tested by treating mice with established P. aeruginosa keratitis with both\ntopical and intravenous treatment modalities. MEDI3902, was shown to be non-toxic to the ocular\nsurface of mice when given topically. It was also effective compared to the control antibody at\npreventing P. aeruginosa keratitis with a one-time treatment at the time of infection. Both topical and\nintravenous administration of MEDI3902 has been proved significant in treating established keratitis\ninfections as well, speeding the resolution of infection significantly more than that of the control IgG.\nWe report the first use of a topical immunotherapeutic multifunctional agent targeting Psl and type\n3 secretion on the ocular surface as an antimicrobial agent. While MEDI3902 has been shown to\nprevent Pseudomonas biofilm formation in keratitis models when given prophylactically intravitally,\nwe show that MEDI3902 has the capability to also treat an active infection when given intravenously\nto mice with Pseudomonas keratitis. Our data indicate antibodies are well tolerated and nontoxic on\nthe ocular surface. They reduce infection in mice treated concurrently at inoculation and reduced\nthe signs of cornea pathology in mice with established infection. Taken together, these data indicate\ntreatment with monoclonal antibodies directed against Psl and PcrV may be clinically effective in the\ntreatment of P. aeruginosa keratitis and suggest that the design of further antibodies to be an additional\ntool in the treatment of bacterial keratitis.
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