Current Recommendations, Antibiotic Resistance, and Emerging Treatments for Gram-Positive Ocular Infections in the United States

Severe bacterial keratitis and endophthalmitis are leading causes of corneal scarring, enucleation, and permanent vision loss, and are increasingly complicated by multidrug-resistant Gram-positive ocular pathogens. In the United States, according to the ARMOR surveillance program (2009–2020), methicillin resistance reached 45.9% of intraocular Staphylococcus aureus and 47.9% of coagulase-negative staphylococci (CoNS), with multidrug resistance exceeding 70% among methicillin-resistant intraocular isolates. While new antibiotics have been approved for systemic infections, vancomycin remains the standard of care for severe Gram-positive ocular infections. However, its ophthalmic use is constrained by limited ocular surface tolerability, physical incompatibility with intravitreal ceftazidime, and an association with hemorrhagic occlusive retinal vasculitis. To address this gap and further stimulate the development of next-generation targeted therapies in ophthalmology, this review focuses on current recommendations and new vancomycin alternative treatments for Gram-positive ocular infections in the antibiotic resistance era. This review details the current antimicrobial recommendations for the most frequent ocular infections, followed by the epidemiology and molecular mechanisms of resistance in S. aureus, CoNS, and S. pneumoniae. Finally, this review discusses new drugs that represent promising alternatives to vancomycin in ophthalmology.