Antimicrobial activity and in vitro corneal epithelial toxicity of antimicrobial agents for Gram-positive corneal pathogens

Abstract

We assessed in vitro the antimicrobial activity of four agents (vancomycin, teicoplanin, mupirocin, and imipenem) which are effective against Gram-positive cocci causally associated with bacterial keratitis, as well as their corneal epithelial cytotoxicity. Minimal inhibitory concentrations inhibiting 90% of strains (MIC₉₀s) against 10 strains each of methicillin-sus-ceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, penicillin-susceptible and -resistant Streptococcus pneumoniae, and viri-dans group streptococci were as follows: vancomycin (MIC₉₀s 0.25–2 μg/ml), teicoplanin (MIC₉₀s 0.25–4 μg/ml, mupirocin (MIC₉₀s 0.12–4 μg/mJ), and imi-penem (MIC₉₀s 0.008–0.25 μg/ml, except for methicillin-resistant staphylococci with MIC₉₀ of 16 μg/ml). Cytotoxicity was assayed by uptake of ³H-thymidine by rabbit corneal epithelial cell cultures at drug concentrations of 12.5–100 mg/ml for vancomycin and teicoplanin, 1–8 mg/ml for mupirocin and 0.125–8 mg/ml for imipenem, with exposure times of 5, 30 and 60 min. Cytotoxicity was as follows: imipenem < mupirocin < vancomycin ≦, teicoplanin. Resistance to methicillin-resistant S. aureus and S. epidermidis for imipenem and resistance to S. epidermidis and cytotoxicity for teicoplanin limit their consideration for suspected Gram-positive keratitis. On the other hand, vancomycin and mupirocin, because of their excellent therapeutic indices, should be considered for this indication.