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

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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-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, penicillin-susceptible and -resistant Streptococcus pneumoniae, and viridans group streptococci were as follows: vancomycin (MIC90s 0.25-2 micrograms/ml), teicoplanin (MIC90s 0.25-4 micrograms/ml, mupirocin (MIC90s 0.12-4 micrograms/ml), and imipenem (MIC90s 0.008-0.25 micrograms/ml, except for methicillin-resistant staphylococci with MIC90 of 16 micrograms/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 < or = 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.

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