In vivo tolerability of topical telavancin versus vancomycin in a murine ocular model.

BACKGROUND

Multicentre surveillance studies show increasing resistance among ocular MDR bacteria causing sight-threatening infections, especially MRSA. MRSA is associated with poor visual outcomes despite treatment with topical fortified vancomycin (25-50 mg/mL), the current standard of care. We previously demonstrated that telavancin exhibits approximately 16-fold greater in vitro potency than vancomycin against ocular MRSA isolates, with lower cytotoxicity.

OBJECTIVES

To compare the in vivo ocular tolerability of topical telavancin and vancomycin at 25 and 50 mg/mL in a murine maximum-tolerated-dose model.

METHODS

Immunocompetent female BALB/c mice (n = 24; six groups, four/group) received 20 instillations, 15 min apart over 5 h, of telavancin or vancomycin (25 or 50 mg/mL) or matching vehicles [250 or 500 mg/mL hydroxy-propyl-β-cyclodextrin (HPβCD) for telavancin; 0.9% NaCl for vancomycin]. Ocular irritation was graded 30 min after the final dose and cage-side observations were recorded 1, 3 and 5 h.

RESULTS

Vancomycin showed dose-dependent toxicity. At 25 mg/mL, all mice (4/4) exhibited hyperaemia, chemosis and eyelid closure; at 50 mg/mL, all had eyelid closure, chemosis, hyperaemia and corneal dryness, and 2/4 had white discharge. Telavancin 25 mg/mL was well tolerated: only 1/4 displayed mild chemosis and squinting, with no eyelid closure. Telavancin 50 mg/mL caused eyelid closure, chemosis and hyperaemia in 4/4 mice. The 250 mg/mL vehicle caused no clinically relevant ocular changes, although 1/4 mice showed squinting; 500 mg/mL vehicle induced mild chemosis and hyperaemia in 4/4 mice.

CONCLUSIONS

The telavancin 25 mg/mL formulation was better tolerated than the fortified vancomycin formulation tested in this model. These findings support further preclinical evaluation for MDR Gram-positive ocular infections.