Overcoming Antimicrobial Resistance in Bacterial Keratitis With an Antibiotic-Eluting Contact Lens.

Abstract

PURPOSE: Bacterial keratitis (BK) is a leading cause of corneal blindness globally, with an alarming rise in resistant infections. Current standard-of-care antibiotic eye drops or ointments suffer from low bioavailability and often fail to achieve therapeutic concentrations in cornea. This study evaluated a therapeutic contact lens (M-TCL) designed to provide sustained, localized high drug concentrations of moxifloxacin-a commonly used broad-spectrum antibiotic-as a potential treatment for drug-resistant BK. METHODS: M-TCLs were engineered by encapsulating a thin moxifloxacin-polymer film within periphery of a contact lens hydrogel. Pharmacokinetics were assessed in rabbit ocular tissues and serum. Efficacy was evaluated using a rabbit keratitis model induced by clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates that displayed in vitro resistance to moxifloxacin (minimum inhibitory concentration = 8 &#xb5;g/mL). Biocompatibility was assessed through Draize testing and histological analysis. RESULTS: In vitro, M-TCLs retained physical properties comparable to commercial contact lenses, sustained moxifloxacin release over 24 hours, and remained stable in a hydrated state for 12 months, enabling on-demand use. In rabbits, M-TCLs maintained higher corneal drug concentrations at all time points over 24 hours than the peak concentration from moxifloxacin drops (P = 0.03), with a 32-fold higher peak drug concentration and at least 11.3-fold greater area under the concentration-time curve (AUC(0-24 h)) in cornea. M-TCLs demonstrated bactericidal efficacy against MRSA keratitis with bacterial reduction of 3.86-log CFU/cornea (P < 0.0001), and mitigated keratitis-associated inflammation with lower aqueous humor protein levels (P = 0.01), compared to hourly moxifloxacin drops. M-TCLs were safe in rabbits. CONCLUSIONS: M-TCLs offer a promising therapy for BK and may serve as a potential therapy for drug-resistant BK.