細菌性角膜炎における抗生物質放出コンタクトレンズによる薬剤耐性の克服

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.

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 µg/mL). Biocompatibility was assessed through Draize testing and histological analysis.

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.

M-TCLs offer a promising therapy for BK and may serve as a potential therapy for drug-resistant BK.